TMA Interview Questions & Answers 2024 PDF

TMA INTERVIEW QUESTIONS&ANSWERS Academic year 2024 oxygen (O), nonmetallic chemical element of Group 16 (VIa, or the oxygen group) of the periodic table. Oxygen is a colourless, odourless, tasteless gas essential to living organisms, being taken up by animals, which convert it to carbon dioxide; plants, in turn, utilize carbon dioxide as a source of carbon and return the oxygen to the atmosphere. Oxygen forms compounds by reaction with practically any other element, as well as by reactions that displace elements from their combinations with each other; in many cases, these processes are accompanied by the evolution of heat and light and in such cases are called combustions. Its most important compound is water. Element Properties atomic number8 atomic weight15.9994 melting point−218.4 °C (−361.1 °F) boiling point−183.0 °C (−297.4 °F) density (1 atm, 0 °C)1.429 g/litre oxidation states−1, −2, +2 (in compounds with fluorine) electron config.1s22s22p4 Preparative methods Production methods chosen for oxygen depend upon the quantity of the element desired. Laboratory procedures include the following: 1. Thermal decomposition of certain salts, such as potassium chlorate or potassium nitrate: The decomposition of potassium chlorate is catalyzed by oxides of transition metals; manganese dioxide (pyrolusite, MnO2) is frequently used. The temperature necessary to effect the evolution of oxygen is reduced from 400 °C to 250 °C by the catalyst. TMA INTERVIEW QUESTIONS&ANSWERS Academic year 2023 2. Thermal decomposition of oxides of heavy metals: Scheele and Priestley used mercury(II) oxide in their preparations of oxygen. 3. Thermal decomposition of metal peroxides or of hydrogen peroxide: 4. Electrolysis of water containing small proportions of salts or acids to allow conduction of the electric current: Chemical properties and reactions TMA INTERVIEW QUESTIONS&ANSWERS Academic year 2023 The large values of the electronegativity and the electron affinity of oxygen are typical of elements that show only nonmetallic behaviour. In all of its compounds, oxygen assumes a negative oxidation state as is expected from the two half-filled outer orbitals. When these orbitals are filled by electron transfer, the oxide ion O2− is created. In peroxides (species containing the ion O22−) it is assumed that each oxygen has a charge of −1. This property of accepting electrons by complete or partial transfer defines an oxidizing agent. When such an agent reacts with an electron-donating substance, its own oxidation state is lowered. The change (lowering), from the zero to the −2 state in the case of oxygen, is called a reduction. Oxygen may be thought of as the “original” oxidizing agent, the nomenclature used to describe oxidation and reduction being based upon this behaviour typical of oxygen. As described in the section on allotropy, oxygen forms the diatomic species, O2, under normal conditions and, as well, the triatomic species ozone, O3. There is some evidence for a very unstable tetratomic species, O4. In the molecular diatomic form there are two unpaired electrons that lie in antibonding orbitals. The paramagnetic behaviour of oxygen confirms the presence of such electrons. The intense reactivity of ozone is sometimes explained by suggesting that one of the three oxygen atoms is in an “atomic” state; on reacting, this atom is dissociated from the O3 molecule, leaving molecular oxygen. The molecular species, O2, is not especially reactive at normal (ambient) temperatures and pressures. The atomic species, O, is far more reactive. The energy of dissociation (O2 → 2O) is large at 117.2 kilocalories per mole. Oxygen has an oxidation state of −2 in most of its compounds. It forms a large range of covalently bonded compounds, among which are oxides of nonmetals, such as water (H2O), sulfur dioxide (SO2), and carbon dioxide (CO2); organic compounds such as alcohols, aldehydes, and carboxylic acids; common acids such as sulfuric (H2SO4), carbonic (H2CO3), and nitric (HNO3); and corresponding salts, such as sodium sulfate (Na2SO4), sodium carbonate (Na2CO3), and sodium nitrate (NaNO3). Oxygen is present as the oxide ion, O2-, in the crystalline structure of solid metallic oxides such as calcium oxide, CaO. Metallic superoxides, such as potassium superoxide, KO2, contain the O2- ion, whereas metallic peroxides, such as barium peroxide, BaO2, contain the O22- ion. chromosome, the microscopic threadlike part of the cell that carries hereditary information in the form of genes. A defining feature of any chromosome is its compactness. For instance, the 46 chromosomes found in human cells have a combined length of 200 nm (1 nm = 10− 9 metre); if the chromosomes were to be unraveled, the genetic material they contain would measure roughly 2 metres (about 6.5 feet) in length. The compactness of chromosomes plays an important role in helping to organize genetic material during cell division and enabling it to fit inside structures such as the nucleus of a cell, the average diameter of which is about 5 to 10 µm (1 µm = 0.00l mm, or 0.000039 inch), or the polygonal head of a virus particle, which may be in the range of just 20 to 30 nm in diameter. TMA INTERVIEW QUESTIONS&ANSWERS Academic year 2023 The structure and location of chromosomes are among the chief differences between viruses, prokaryotes, and eukaryotes. The nonliving viruses have chromosomes consisting of either DNA (deoxyribonucleic acid) or RNA (ribonucleic acid); this material is very tightly packed into the viral head. Among organisms with prokaryotic cells (i.e., bacteria and blue-green algae), chromosomes consist entirely of DNA. The single chromosome of a prokaryotic cell is not enclosed within a nuclear membrane. Among eukaryotes, the chromosomes are contained in a membrane-bound cell nucleus. The chromosomes of a eukaryotic cell consist primarily of DNA attached to a protein core. They also contain RNA. The remainder of this article pertains to eukaryotic chromosomes. Every eukaryotic species has a characteristic number of chromosomes (chromosome number). In species that reproduce asexually, the chromosome number is the same in all the cells of the organism. Among sexually reproducing organisms, the number of chromosomes in the body (somatic) cells is diploid (2n; a pair of each chromosome), twice the haploid (1n) number found in the sex cells, or gametes. The haploid number is produced during meiosis. During fertilization, two gametes combine to produce a zygote, a single cell with a diploid set of chromosomes. Somatic cells reproduce by dividing, a process called mitosis. Between cell divisions the chromosomes exist in an uncoiled state, producing a diffuse mass of genetic material known as chromatin. The uncoiling of chromosomes enables DNA synthesis to begin. During this phase, DNA duplicates itself in preparation for cell division. Following replication, the DNA condenses into chromosomes. At this point, each chromosome actually consists of a set of duplicate chromatids that are held together by the centromere. The centromere is the point of attachment of the kinetochore, a protein structure that is connected to the spindle fibres (part of a structure that pulls the chromatids to opposite ends of the cell). During the middle stage in cell division, the centromere duplicates, and the chromatid pair separates; each chromatid becomes a separate chromosome at this point. The cell divides, and both of the daughter cells have a complete (diploid) set of chromosomes. The chromosomes uncoil in the new cells, again forming the diffuse network of chromatin. Among many organisms that have separate sexes, there are two basic types of chromosomes: sex chromosomes and autosomes. Autosomes control the inheritance of all the characteristics except the sex-linked ones, which are controlled by the sex chromosomes. Humans have 22 pairs of autosomes and one pair of sex chromosomes. All act in the same way during cell division. For information on sex-linked characteristics, see linkage group bone, rigid body tissue consisting of cells embedded in an abundant hard intercellular material. The two principal components of this material, collagen and calcium phosphate, distinguish bone from such other hard tissues as chitin, enamel, and shell. Bone tissue makes up the individual bones of the human skeletal system and the skeletons of other vertebrates. The functions of bone include (1) structural support for the mechanical action of soft tissues, such as the contraction of muscles and the expansion of lungs, (2) protection TMA INTERVIEW QUESTIONS&ANSWERS Academic year 2023 of soft organs and tissues, as by the skull, (3) provision of a protective site for specialized tissues such as the blood-forming system (bone marrow), and (4) a mineral reservoir, whereby the endocrine system regulates the level of calcium and phosphate in the circulating body fluids. Chemical composition and physical properties Depending upon species, age, and type of bone, bone cells represent up to 15 percent of the volume of bone; in mature bone in most higher animals, they usually represent only up to 5 percent. The nonliving intercellular material of bone consists of an organic component called collagen (a fibrous protein arranged in long strands or bundles similar in structure and organization to the collagen of ligaments, tendons, and skin), with small amounts of proteinpolysaccharides, glycoaminoglycans (formerly known as mucopolysaccharides) chemically bound to protein and dispersed within and around the collagen fibre bundles, and an inorganic mineral component in the form of rod- shaped crystals. These crystals are arranged parallel with the long axes of collagen bundles and many actually lie in voids within the bundles themselves. Organic material constitutes 50 percent of the volume and 30 percent of the dry weight of the intercellular composite, with minerals making up the remainder. The major minerals of the intercellular composite are calcium and phosphate. When first deposited, mineral is crystallographically amorphous, but with maturation it becomes typical of the apatite minerals, the major component being hydroxyapatite. Carbonate is also present—in amounts varying from 4 percent of bone ash in fish and 8 percent in most mammals to more than 13 percent in the turtle—and occurs in two distinct phases, calcium carbonate and a carbonate apatite. Except for that associated with its cellular elements, there is little free water in adult mammalian bone (approximately 8 percent of total volume). As a result, diffusion from surfaces into the interior of the intercellular substance occurs at the slow rates more typical of diffusion from surfaces of solids than within liquids. The mineral crystals are responsible for hardness, rigidity, and the great compressive strength of bone, but they share with other crystalline materials a great weakness in tension, arising from the tendency for stress to concentrate about defects and for these defects to propagate. On the other hand, the collagen fibrils of bone possess high elasticity, little compressive strength, and considerable intrinsic tensile strength. The tensile strength of bone depends, however, not on collagen alone but on the intimate association of mineral with collagen, which confers on bone many of the general properties exhibited by two-phase materials such as fibre glass and bamboo. In such materials the dispersion of a rigid but brittle material in a matrix of quite different elasticity prevents the propagation of stress failure through the brittle material and therefore allows a closer approach to the theoretical limiting strength of single crystals. The fine structure of bone has thus far frustrated attempts to determine the true strength of the mineral-matrix composite at the “unit” structural level. Compact (cortical) bone specimens have been found to have tensile strength in the range of 700–1,400 kg per square cm (10,000–20,000 pounds per square inch) and compressive strengths in the range of 1,400–2,100 kg per square cm (20,000–30,000 TMA INTERVIEW QUESTIONS&ANSWERS Academic year 2023 pounds per square inch). These values are of the same general order as for aluminum or mild steel, but bone has an advantage over such materials in that it is considerably lighter. The great strength of bone exists principally along its long axis and is roughly parallel both to the collagen fibre axis and to the long axis of the mineral crystals. Although apparently stiff, bones exhibit a considerable degree of elasticity, which is important to the skeleton’s ability to withstand impact. Estimates of modulus of elasticity of bone samples are of the order of 420 to 700 kg per square cm (6,000 to 10,000 pounds per square inch), a value much less than steel, for example, indicating the much greater elasticity of bone. Perfect elasticity exists with loads up to 30 to 40 percent of breaking strength; above this, “creep,” or gradual deformation, occurs, presumably along natural defects within the bony structure. The modulus of elasticity in bone is strikingly dependent upon the rate at which loads are applied, bones being stiffer during rapid deformation than during slow; this behaviour suggests an element of viscous flow during deformation. As might be anticipated from consideration of the two-phase composition of bone, variation in the mineral-collagen ratio leads to changes in physical properties: less mineral tends ultimately to greater flexibility and more mineral to increased brittleness. Optimal ratios, as reflected in maximal tensile strength, are observed at an ash content of approximately 66 percent, a value that is characteristic of the weight- bearing bones of mammals. Bone morphology Grossly, bone tissue is organized into a variety of shapes and configurations adapted to the function of each bone: broad, flat plates, such as the scapula, serve as anchors for large muscle masses, while hollow, thick-walled tubes, such as the femur, the radius, and the ulna, support weight or serve as a lever arm. These different types of bone are distinguished more by their external shape than by their basic structure Microscopically, bone consists of hard, apparently homogeneous intercellular material, within or upon which can be found four characteristic cell types: osteoblasts, osteocytes, osteoclasts, and undifferentiated bone mesenchymal stem cells. Osteoblasts are responsible for the synthesis and deposition on bone surfaces of the protein matrix of new intercellular material. Osteocytes are osteoblasts that have been trapped within intercellular material, residing in a cavity (lacuna) and communicating with other osteocytes as well as with free bone surfaces by means of extensive filamentous protoplasmic extensions that occupy long, meandering channels (canaliculi) through the bone substance. With the exception of certain higher orders of modern fish, all bone, including primitive vertebrate fossil bone, exhibits an osteocytic structure. Osteoclasts are usually large multinucleated cells that, working from bone surfaces, resorb bone by direct chemical and enzymatic attack. Undifferentiated mesenchymal stem cells of the bone reside in the loose connective tissue between trabeculae, along vascular channels, and in the condensed fibrous tissue covering the outside of the bone (periosteum); they give rise under appropriate stimuli to osteoblasts. Depending on how the protein fibrils and osteocytes of bone are arranged, bone is of two major types: woven, in which collagen bundles and the long axes of the osteocytes TMA INTERVIEW QUESTIONS&ANSWERS Academic year 2023 are randomly oriented, and lamellar, in which both the fibrils and osteocytes are aligned in clear layers. In lamellar bone the layers alternate every few micrometres (millionths of a metre), and the primary direction of the fibrils shifts approximately 90°. In compact, or cortical, bone of many mammalian species, lamellar bone is further organized into units known as osteons, which consist of concentric cylindrical lamellar elements several millimetres long and 0.2–0.3 mm (0.008–0.012 inch) in diameter. These cylinders comprise the haversian systems. Osteons exhibit a gently spiral course oriented along the axis of the bone. In their centre is a canal (haversian canal) containing one or more small blood vessels, and at their outer margins is a boundary layer known as a “cement line,” which serves both as a means of fixation for new bone deposited on an old surface and as a diffusion barrier. Osteocytic processes do not penetrate the cement line, and therefore these barriers constitute the outer envelope of a nutritional unit; osteocytes on opposite sides of a cement line derive their nutrition from different vascular channels. Cement lines are found in all types of bone, as well as in osteons, and in general they indicate lines at which new bone was deposited on an old surface. Vascular supply and circulation In a typical long bone, blood is supplied by three separate systems: a nutrient artery, periosteal vessels, and epiphyseal vessels. The diaphysis and metaphysis are nourished primarily by the nutrient artery, which passes through the cortex into the medullary cavity and then ramifies outward through haversian and Volkmann canals to supply the cortex. Extensive vessels in the periosteum, the membrane surrounding the bone, supply the superficial layers of the cortex and connect with the nutrient-artery system. In the event of obstruction of the nutrient artery, periosteal vessels are capable of meeting the needs of both systems. The epiphyses are supplied by a separate system that consists of a ring of arteries entering the bone along a circular band between the growth plate and the joint capsule. In the adult these vessels become connected to the other two systems at the metaphyseal-epiphyseal junction, but while the growth plate is open there is no such connection, and the epiphyseal vessels are the sole source of nutrition for the growing cartilage; therefore they are essential for skeletal growth. Drainage of blood is by a system of veins that runs parallel with the arterial supply and by veins leaving the cortical periosteum through muscle insertions. Muscle contraction milks blood outward, giving rise to a centrifugal pattern of flow from the axial nutrient artery through the cortex and out through muscle attachments Physiology of bone As important as the structural properties of bone is the role bone plays in the maintenance of the ionic composition of the blood and interstitial fluids of the body. All vertebrates possessing true bone exhibit body-fluid calcium ion concentrations of approximately 50 mg per litre (1.25 millimoles) and phosphorus concentrations in the range of 30–100 mg per litre (1–3 millimoles). These levels, particularly those of calcium, are extremely important for the maintenance of normal neuromuscular function, interneuronal transmission, cell membrane integrity and permeability, and blood coagulation. The rigid constancy with which calcium levels are maintained, both in the individual and throughout all higher vertebrate classes, attests to the biological importance of such regulation. Approximately 99 percent of total body calcium and 85 TMA INTERVIEW QUESTIONS&ANSWERS Academic year 2023 percent of total body phosphorus reside in the mineral deposits of bone; thus, bone is quantitatively in a position to mediate adjustments in concentration of these two ions in the circulating body fluids. Such adjustments are provided by three hormonal control loops (control systems with feedback) and by at least three locally acting mechanisms. The hormonal loops involve parathyroid hormone (PTH), calcitonin (CT), and vitamin D and are concerned exclusively with regulation of calcium ion and phosphorus ion concentrations. PTH and vitamin D act to elevate ionized calcium levels in body fluids, and CT (from the ultimobranchial body or C cells of the thyroid gland) acts to depress them. The secretion of each hormone is controlled by the level of calcium ion in the circulating blood. At normal calcium concentrations, there are low levels of secretion of all three hormones. When the blood levels of ionized calcium decline, there is an almost immediate increase in PTH synthesis and secretion. PTH has three principal actions in maintaining blood calcium concentrations. It directly stimulates the kidneys to enhance the tubular reabsorption of calcium from the ultrafiltrate that would otherwise be excreted into the urine. It also stimulates the kidney to activate the major circulating form of vitamin D to calcitrial. Calcitrial enters the circulation and travels to the small intestine where it acts to increase the absorption efficiency of dietary calcium into the bloodstream. PTH and calcitrial can also stimulate osteoblasts to produce osteoclast differentiation factor (ODF). Osteoblasts that have ODF on their surfaces can interact with the precursor cells of osteoclasts (monocytes) to induce them to become mature osteoclasts. The osteoclasts in turn release hydrochloric acid and enzymes into the mineralized bone and release calcium and phosphorus into the circulation. Thus, when there is inadequate dietary calcium to satisfy the body’s calcium needs, both PTH and calcitrial work in concert on osteoblasts to recruit precursors of osteoclasts to become mature osteoclasts. When the body’s calcium needs are satisfied by adequate dietary intake of calcium, both PTH and calcitrial act on osteoblasts to increase their activity, resulting in increased bone formation and mineralization. Calcitonin is the only hormone that interacts directly on osteoclasts, which have a receptor for it. It decreases mature osteoclastic activity, thereby inhibiting their function. PTH and calcitrial also are important in maintaining serum phosphorus levels. PTH interferes with renal tubular phosphorus reabsorption, causing an enhanced renal excretion of phosphorus. This mechanism, which serves to lower levels of phosphorus in the bloodstream, is significant because high phosphate levels inhibit and low levels enhance osteoclastic reabsorption. Calcium ion itself has similar effects on the osteoclastic process: high levels inhibit and low levels enhance the effect of systemically acting agents such as PTH. On the other hand, PTH stimulates the production of calcitrial, which in turn stimulates the small intestine to increase its efficacy of absorption of dietary phosphorus. A deficiency in vitamin D results in poor mineralization of the skeleton, causing rickets in children and osteomalacia in adults. Mineralization defects are due to the decrease in the efficiency of intestinal calcium absorption, which results in a decrease in ionized calcium concentrations in blood. This results in an increase in PTH in the circulation, which increases serum calcium and decreases serum phosphorus because of the enhanced excretion of phosphorus into the urine. TMA INTERVIEW QUESTIONS&ANSWERS Academic year 2023 The exact function of calcitonin is not fully understood. However, it can offset elevations in high calcium ion levels by decreasing osteoclast activity, resulting in inhibition of bone absorption. lipid, any of a diverse group of organic compounds including fats, oils, hormones, and certain components of membranes that are grouped together because they do not interact appreciably with water. One type of lipid, the triglycerides, is sequestered as fat in adipose cells, which serve as the energy-storage depot for organisms and also provide thermal insulation. Some lipids such as steroid hormones serve as chemical messengers between cells, tissues, and organs, and others communicate signals between biochemical systems within a single cell. The membranes of cells and organelles (structures within cells) are microscopically thin structures formed from two layers of phospholipid molecules. Membranes function to separate individual cells from their environments and to compartmentalize the cell interior into structures that carry out special functions. So important is this compartmentalizing function that membranes, and the lipids that form them, must have been essential to the origin of life itself. Fatty acids rarely occur as free molecules in nature but are usually found as components of many complex lipid molecules such as fats (energy-storage compounds) and phospholipids (the primary lipid components of cellular membranes). This section describes the structure and physical and chemical properties of fatty acids. It also explains how living organisms obtain fatty acids, both from their diets and through metabolic breakdown of stored fats Biological fatty acids, members of the class of compounds known as carboxylic acids, are composed of a hydrocarbon chain with one terminal carboxyl group (COOH). The fragment of a carboxylic acid not including the hydroxyl (OH) group is called an acyl group. Under physiological conditions in water, this acidic group usually has lost a hydrogen ion (H+) to form a negatively charged carboxylate group (COO−). Most biological fatty acids contain an even number of carbon atoms because the biosynthetic pathway common to all organisms involves chemically linking two- carbon units together (although relatively small amounts of odd-number fatty acids do occur in some organisms). Although the molecule as a whole is water-insoluble by virtue of its hydrophobic hydrocarbon chain, the negatively charged carboxylate is hydrophilic. This common form for biological lipids—one that contains well-separated hydrophobic and hydrophilic parts—is called amphipathic. In addition to straight-chain hydrocarbons, fatty acids may also contain pairs of carbons linked by one or more double bonds, methyl branches, or a three-carbon cyclopropane ring near the centre of the carbon chain. TMA INTERVIEW QUESTIONS&ANSWERS Academic year 2023 Saturated fatty acids The simplest fatty acids are unbranched, linear chains of CH2 groups linked by carbon- carbon single bonds with one terminal carboxylic acid group. The term saturated indicates that the maximum possible number of hydrogen atoms are bonded to each carbon in the molecule. Many saturated fatty acids have a trivial or common name as well as a chemically descriptive systematic name. The systematic names are based on numbering the carbon atoms, beginning with the acidic carbon. The table gives the names and typical biological sources of the most common saturated fatty acids. Although the chains are usually between 12 and 24 carbons long, several shorter-chain fatty acids are biochemically important. For instance, butyric acid (C4) and caproic acid (C6) are lipids found in milk. Palm kernel oil, an important dietary source of fat in certain areas of the world, is rich in fatty acids that contain 8 and 10 carbons (C8 and C10). Common saturated fatty acids trivial name systematic name number of carbons in chain typical sources lauric acid n-dodecanoic acid 12 palm kernel oil, nutmeg myristic acid n-tetradecanoic acid 14 palm kernel oil, nutmeg palmitic acid n-hexadecanoic acid 16 olive oil, animal lipids stearic acid n-octadecanoic acid 18 cocoa butter, animal lipids behenic acid n-docosanoic acid 22 brain tissue, radish oil lignoceric acid n-tetracosanoic acid 24 brain tissue, carnauba wax Unsaturated fatty acids Unsaturated fatty acids have one or more carbon-carbon double bonds. The term unsaturated indicates that fewer than the maximum possible number of hydrogen atoms are bonded to each carbon in the molecule. The number of double bonds is indicated by the generic name—monounsaturated for molecules with one double bond or polyunsaturated for molecules with two or more double bonds. Oleic acid is an example of a monounsaturated fatty acid. Common representative monounsaturated fatty acids together with their names and typical sources are listed in the table. The prefix cis-9 in the systematic name of palmitoleic acid denotes that the position of the double bond is between carbons 9 and 10. Two possible conformations, cis and trans, can be taken by the two CH2 groups immediately adjacent to the double-bonded carbons. In the cis configuration, the one occurring in all biological unsaturated fatty acids, the two adjacent carbons lie on the same side of the double-bonded carbons. In the trans configuration, the two adjacent carbons lie on opposite sides of the double-bonded carbons. TMA INTERVIEW QUESTIONS&ANSWERS Academic year 2023 Common monounsaturated fatty acids trivial name systematic name number of carbons in chain typical sources palmitoleic acid cis-9-hexadecenoic acid 16 marine algae, pine oil oleic acid cis-9-octadecenoic acid 18 animal tissues, olive oil gadoleic acid cis-9-eicosenoic acid 20 fish oils (cod, sardine) erucic acid cis-13-docosenoic acid 22 rapeseed oil nervonic acid cis-15-tetracosenoic acid 24 sharks, brain tissue Fatty acids containing more than one carbon-carbon double bond (polyunsaturated fatty acids) are found in relatively minor amounts. The multiple double bonds are almost always separated by a CH2 group (―CH2―CH=CH―CH2―CH=CH―CH2―), a regular spacing motif that is the result of the biosynthetic mechanism by which the double bonds are introduced into the hydrocarbon chain. The table lists the most common polyunsaturated fatty acids, linoleic and arachidonic, together with several that are less common. Arachidonic acid (C20) is of particular interest as the precursor of a family of molecules, known as eicosanoids (from Greek eikosi, “twenty”), that includes prostaglandins, thromboxanes, and leukotrienes. These compounds, produced by cells under certain conditions, have potent physiological properties, as explained in the section Intracellular and extracellular messengers. Animals cannot synthesize two important fatty acids, linoleic acid (an omega-6 fatty acid) and alpha-linolenic acid (an omega-3 fatty acid), that are the precursors of the eicosanoids and so must obtain them in the diet from plant sources. For this reason, these precursors are called essential fatty acids. Common polyunsaturated fatty acids number of carbons trivial name systematic name typical sources in chain cis-9-, cis-12-octadecadienoic corn oil, animal tissues, linoleic acid 18 acid bacteria linolenic acid cis-9-, cis-12-, cis-15- 18 animal tissues octadecatrienoic acid 5,8,11-eicosatrienoic acid 20 8,11,14-eicosatrienoic acid 20 brain tissue 7,10,13-docosatrienoic acid 22 phospholipids 8,11,14-docosatrienoic acid 22 arachidonic 5,8,11,14-eicosatetraenoic acid 20 liver, brain tissue acid 4,7,10,13-docosatetraenoic acid 22 brain tissue TMA INTERVIEW QUESTIONS&ANSWERS Academic year 2023 Common polyunsaturated fatty acids number of carbons trivial name systematic name typical sources in chain 4,7,10,13,16,19- 22 brain tissue docosahexaenoic acid Trans polyunsaturated fatty acids, although not produced biosynthetically by mammals, are produced by microorganisms in the gut of ruminant animals such as cows and goats, and they are also produced synthetically by partial hydrogenation of fats and oils in the manufacture of margarine (the so-called trans fats). There is evidence that ingestion of trans fats can have deleterious metabolic effects. Substituent groups In addition to the very common fatty acids with straight saturated or unsaturated acyl chains, many fatty acids are chemically modified by substituents on the hydrocarbon chain. For example, the preening gland of ducks secretes a fatty acid 10 carbons long with methyl (CH3) groups substituted for one of the hydrogens on carbons 2, 4, 6, and 8. Some bacteria produce fatty acids that have a methyl group on the carbon atom farthest from the acidic group or on the penultimate carbon. Other bacteria incorporate a cyclopropane ring near the centre of the acyl chain. The bacterium that causes tuberculosis (Mycobacterium tuberculosis) synthesizes a whole family of cyclopropane-containing fatty acids called α-mycolic acids. Similar fatty acids are found in related bacteria. A third common constituent is a hydroxyl group (OH). Monohydroxyl acids are found in both plants and animals in relatively small amounts, but they are more prevalent in bacteria Biological sources Fatty acids are found in biological systems either as free molecules or as components of more-complex lipids. They are derived from dietary sources or produced by metabolism, as described below. Digestion of dietary fatty acids The main source of fatty acids in the diet is triglycerides, generically called fats. In humans, fat constitutes an important part of the diet, and in some countries it can contribute as much as 45 percent of energy intake. Triglycerides consist of three fatty acid molecules, each linked by an ester bond to one of the three OH groups of a glycerol molecule. After ingested triglycerides pass through the stomach and into the small intestine, detergents called bile salts are secreted by the liver via the gall bladder and disperse the fat as micelles. Pancreatic enzymes called lipases then hydrolyze the dispersed fats to give monoglycerides and free fatty acids. These products are absorbed into the cells lining the small intestine, where they are resynthesized into triglycerides. The triglycerides, together with other types of lipids, are then secreted by these cells in lipoproteins, large molecular complexes that are transported in the lymph and blood to recipient organs. In detail, the process of triglyceride or fat absorption from dietary sources is quite complex and differs somewhat depending upon the animal species. Storage TMA INTERVIEW QUESTIONS&ANSWERS Academic year 2023 After transport through the circulation, triglycerides are hydrolyzed yet again to fatty acids in the adipose tissue. There they are transported into adipose cells, where once again they are resynthesized into triglycerides and stored as droplets. Fat or adipose tissue essentially consists of cells, whereby the interior of each cell is largely occupied by a fat droplet. The triglyceride in these droplets is available to the body on demand as communicated to adipose tissue by hormone messengers. Various animals store triglycerides in different ways. In sharks, for example, fat is stored in the liver, but in bony fish it is deposited in and around muscle fibres. Insects store fat in a special organ called the fat body. The development of true adipose tissue is found only in higher animals. Biosynthesis In mammals, fatty acids are synthesized in adipose and liver cells from glucose via a fairly complex pathway. In essence, the six carbons of a glucose molecule are oxidized to a pair of two-carbon carboxylic acid fragments called acetate. The starting point for biosynthesis is an acetate group chemically linked to a molecule of CoA (coenzyme A). The process of building up the acyl chain of a fatty acid then begins, basically through the sequential chemical addition of two-carbon fragments from CoA-acetate to generate, for example, the 16-carbon saturated fatty acid palmitate. This process is catalyzed by a complex enzyme known as fatty acid synthase. Elongation of the palmitate carbon chain and the introduction of carbon-carbon double bonds are carried out subsequently by other enzyme systems. The overall process is basically the same in organisms ranging from bacteria to humans. red blood cell, also called erythrocyte, cellular component of blood, millions of which in the circulation of vertebrates give the blood its characteristic colour and carry oxygen from the lungs to the tissues. The mature human red blood cell is small, round, and biconcave; it appears dumbbell-shaped in profile. The cell is flexible and assumes a bell shape as it passes through extremely small blood vessels. It is covered with a membrane composed of lipids and proteins, lacks a nucleus, and contains hemoglobin—a red iron-rich protein that binds oxygen. TMA INTERVIEW QUESTIONS&ANSWERS Academic year 2023 Observe how a red blood cell travels from the heart to the lungs and other body tissues to exchange oxygen and carbon dioxide See all videos for this article The red cell develops in bone marrow in several stages: from a hemocytoblast, a multipotential cell in the mesenchyme, it becomes an erythroblast (normoblast); during two to five days of development, the erythroblast gradually fills with hemoglobin, and its nucleus and mitochondria (particles in the cytoplasm that provide energy for the cell) disappear. In a late stage the cell is called a reticulocyte, which ultimately becomes a fully mature red cell. The average red cell in humans lives 100–120 days; there are some 5.2 million red cells per cubic millimetre of blood in the adult human. TMA INTERVIEW QUESTIONS&ANSWERS Academic year 2023 red blood cells Though red cells are usually round, a small proportion are oval in the normal person, and in certain hereditary states a higher proportion may be oval. Some diseases also display red cells of abnormal shape—e.g., oval in pernicious anemia, crescent-shaped in sickle cell anemia, and with projections giving a thorny appearance in the hereditary disorder acanthocytosis. The number of red cells and the amount of hemoglobin vary among different individuals and under different conditions; the number is higher, for example, in persons who live at high altitudes and in the disease polycythemia. At birth the red cell count is high; it falls shortly after birth and gradually rises to the adult level at puberty. The design of the respiratory system The human gas-exchanging organ, the lung, is located in the thorax, where its delicate tissues are protected by the bony and muscular thoracic cage. The lung provides the tissues of the human body with a continuous flow of oxygen and clears the blood of the gaseous waste product, carbon dioxide. Atmospheric air is pumped in and out regularly through a system of pipes, called conducting airways, which join the gas- exchange region with the outside of the body. The airways can be divided into upper and lower airway systems. The transition between the two systems is located where the pathways of the respiratory and digestive systems cross, just at the top of the larynx The upper airway system comprises the nose and the paranasal cavities (or sinuses), the pharynx (or throat), and partly also the oral cavity, since it may be used for breathing. The lower airway system consists of the larynx, the trachea, the stem bronchi, and all the airways ramifying intensively within the lungs, such as the intrapulmonary bronchi, the bronchioles, and the alveolar ducts. For respiration, the collaboration of other organ systems is clearly essential. The diaphragm, as the main respiratory muscle, and the intercostal muscles of the chest wall play an essential role by generating, under the control of the central nervous system, the pumping action on the lung. The muscles expand and contract the internal space of the thorax, the bony framework of which is formed by the ribs and the thoracic vertebrae. The contribution of the lung and chest wall (ribs and muscles) to respiration is described below in The mechanics of breathing. The blood, as a carrier for the gases, and the circulatory system (i.e., the heart and the blood vessels) are mandatory elements of a working respiratory system (see blood; cardiovascular system). Morphology of the upper airways The nose The nose is the external protuberance of an internal space, the nasal cavity. It is subdivided into a left and right canal by a thin medial cartilaginous and bony wall, the nasal septum. Each canal opens to the face by a nostril and into the pharynx by the choana. The floor of the nasal cavity is formed by the palate, which also forms the roof of the oral cavity. The complex shape of the nasal cavity is due to projections of bony TMA INTERVIEW QUESTIONS&ANSWERS Academic year 2023 ridges, the superior, middle, and inferior turbinate bones (or conchae), from the lateral wall. The passageways thus formed below each ridge are called the superior, middle, and inferior nasal meatuses. On each side, the intranasal space communicates with a series of neighbouring air- filled cavities within the skull (the paranasal sinuses) and also, via the nasolacrimal duct, with the lacrimal apparatus in the corner of the eye. The duct drains the lacrimal fluid into the nasal cavity. This fact explains why nasal respiration can be rapidly impaired or even impeded during weeping: the lacrimal fluid is not only overflowing into tears, it is also flooding the nasal cavity. The paranasal sinuses are sets of paired single or multiple cavities of variable size. Most of their development takes place after birth, and they reach their final size toward age 20. The sinuses are located in four different skull bones—the maxilla, the frontal, the ethmoid, and the sphenoid bones. Correspondingly, they are called the maxillary sinus, which is the largest cavity; the frontal sinus; the ethmoid sinuses; and TMA INTERVIEW QUESTIONS&ANSWERS Academic year 2023 the sphenoid sinus, which is located in the upper posterior wall of the nasal cavity. The sinuses have two principal functions: because they are filled with air, they help keep the weight of the skull within reasonable limits, and they serve as resonance chambers for the human voice. The nasal cavity with its adjacent spaces is lined by a respiratory mucosa. Typically, the mucosa of the nose contains mucus-secreting glands and venous plexuses; its top cell layer, the epithelium, consists principally of two cell types, ciliated and secreting cells. This structural design reflects the particular ancillary functions of the nose and of the upper airways in general with respect to respiration. They clean, moisten, and warm the inspired air, preparing it for intimate contact with the delicate tissues of the gas-exchange area. During expiration through the nose, the air is dried and cooled, a process that saves water and energy. Two regions of the nasal cavity have a different lining. The vestibule, at the entrance of the nose, is lined by skin that bears short thick hairs called vibrissae. In the roof of the nose, the olfactory bulb with its sensory epithelium checks the quality of the inspired air. About two dozen olfactory nerves convey the sensation of smell from the olfactory cells through the bony roof of the nasal cavity to the central nervous system. The pharynx human pharynx For the anatomical description, the pharynx can be divided into three floors. The upper floor, the nasopharynx, is primarily a passageway for air and secretions from the nose to the oral pharynx. It is also connected to the tympanic cavity of the middle ear through the auditory tubes that open on both lateral walls. The act of swallowing opens briefly the normally collapsed auditory tubes and allows the middle ears to be aerated and pressure differences to be equalized. In the posterior wall of the nasopharynx is located a lymphatic organ, the pharyngeal tonsil. When it is enlarged (as in tonsil hypertrophy or adenoid vegetation), it may interfere with nasal respiration and alter the resonance pattern of the voice. TMA INTERVIEW QUESTIONS&ANSWERS Academic year 2023 The middle floor of the pharynx connects anteriorly to the mouth and is therefore called the oral pharynx or oropharynx. It is delimited from the nasopharynx by the soft palate, which roofs the posterior part of the oral cavity. The lower floor of the pharynx is called the hypopharynx. Its anterior wall is formed by the posterior part of the tongue. Lying directly above the larynx, it represents the site where the pathways of air and food cross each other: Air from the nasal cavity flows into the larynx, and food from the oral cavity is routed to the esophagus directly behind the larynx. The epiglottis, a cartilaginous, leaf-shaped flap, functions as a lid to the larynx and, during the act of swallowing, controls the traffic of air and food. Morphology of the lower airways The larynx The larynx is an organ of complex structure that serves a dual function: as an air canal to the lungs and a controller of its access, and as the organ of phonation. Sound is produced by forcing air through a sagittal slit formed by the vocal cords, the glottis. This causes not only the vocal cords but also the column of air above them to vibrate. As evidenced by trained singers, this function can be closely controlled and finely tuned. Control is achieved by a number of muscles innervated by the laryngeal nerves. For the precise function of the muscular apparatus, the muscles must be anchored to a stabilizing framework. The laryngeal skeleton consists of almost a dozen pieces of cartilage, most of them very small, interconnected by ligaments and membranes. The largest cartilage of the larynx, the thyroid cartilage, is made of two plates fused anteriorly in the midline. At the upper end of the fusion line is an incision, the thyroid notch; below it is a forward projection, the laryngeal prominence. Both of these structures are easily felt through the skin. The angle between the two cartilage plates is sharper and the prominence more marked in men than in women, which has given this structure the common name of Adam’s apple. voice-producing apparatus TMA INTERVIEW QUESTIONS&ANSWERS Academic year 2023 Behind the shieldlike thyroid cartilage, the vocal cords span the laryngeal lumen. They correspond to elastic ligaments attached anteriorly in the angle of the thyroid shield and posteriorly to a pair of small pyramidal pieces of cartilage, the arytenoid cartilages. The vocal ligaments are part of a tube, resembling an organ pipe, made of elastic tissue. Just above the vocal cords, the epiglottis is also attached to the back of the thyroid plate by its stalk. The cricoid, another large cartilaginous piece of the laryngeal skeleton, has a signet-ring shape. The broad plate of the ring lies in the posterior wall of the larynx and the narrow arch in the anterior wall. The cricoid is located below the thyroid cartilage, to which it is joined in an articulation reinforced by ligaments. The transverse axis of the joint allows a hingelike rotation between the two cartilages. This movement tilts the cricoid plate with respect to the shield of the thyroid cartilage and hence alters the distance between them. Because the arytenoid cartilages rest upright on the cricoid plate, they follow its tilting movement. This mechanism plays an important role in altering length and tension of the vocal cords. The arytenoid cartilages articulate with the cricoid plate and hence are able to rotate and slide to close and open the glottis. Viewed frontally, the lumen of the laryngeal tube has an hourglass shape, with its narrowest width at the glottis. Just above the vocal cords there is an additional pair of mucosal folds called the false vocal cords or the vestibular folds. Like the true vocal cords, they are also formed by the free end of a fibroelastic membrane. Between the vestibular folds and the vocal cords, the laryngeal space enlarges and forms lateral pockets extending upward. This space is called the ventricle of the larynx. Because the gap between the vestibular folds is always larger than the gap between the vocal cords, the latter can easily be seen from above with the laryngoscope, an instrument designed for visual inspection of the interior of the larynx. The muscular apparatus of the larynx comprises two functionally distinct groups. The intrinsic muscles act directly or indirectly on the shape, length, and tension of the vocal cords. The extrinsic muscles act on the larynx as a whole, moving it upward (e.g., during high-pitched phonation or swallowing) or downward. The intrinsic muscles attach to the skeletal components of the larynx itself; the extrinsic muscles join the laryngeal skeleton cranially to the hyoid bone or to the pharynx and caudally to the sternum (breastbone). The trachea and the stem bronchi Below the larynx lies the trachea, a tube about 10 to 12 cm (3.9 to 4.7 inches) long and 2 cm (0.8 inch) wide. Its wall is stiffened by 16 to 20 characteristic horseshoe-shaped, incomplete cartilage rings that open toward the back and are embedded in a dense connective tissue. The dorsal wall contains a strong layer of transverse smooth muscle fibres that spans the gap of the cartilage. The interior of the trachea is lined by the typical respiratory epithelium. The mucosal layer contains mucous glands. At its lower end, the trachea divides in an inverted Y into the two stem (or main) bronchi, one each for the left and right lung. The right main bronchus has a larger diameter, is oriented more vertically, and is shorter than the left main bronchus. The practical consequence of this arrangement is that foreign bodies passing beyond the larynx will usually slip into the right lung. The structure of the stem bronchi closely matches that of the trachea. TMA INTERVIEW QUESTIONS&ANSWERS Academic year 2023 Structural design of the airway tree trachea, bronchi, and bronchioles of the human airway tree The hierarchy of the dividing airways, and partly also of the blood vessels penetrating the lung, largely determines the internal lung structure. Functionally the intrapulmonary airway system can be subdivided into three zones, a proximal, purely conducting zone, a peripheral, purely gas-exchanging zone, and a transitional zone in between, where both functions grade into one another. From a morphological point of view, however, it makes sense to distinguish the relatively thick-walled, purely air- conducting tubes from those branches of the airway tree structurally designed to permit gas exchange. The structural design of the airway tree is functionally important because the branching pattern plays a role in determining air flow and particle deposition. In TMA INTERVIEW QUESTIONS&ANSWERS Academic year 2023 modeling the human airway tree, it is generally agreed that the airways branch according to the rules of irregular dichotomy. Regular dichotomy means that each branch of a treelike structure gives rise to two daughter branches of identical dimensions. In irregular dichotomy, however, the daughter branches may differ greatly in length and diameter. The models calculate the average path from the trachea to the lung periphery as consisting of about 24–25 generations of branches. Individual paths, however, may range from 11 to 30 generations. The transition between the conductive and the respiratory portions of an airway lies on average at the end of the 16th generation, if the trachea is counted as generation 0. The conducting airways comprise the trachea, the two stem bronchi, the bronchi, and the bronchioles. Their function is to further warm, moisten, and clean the inspired air and distribute it to the gas-exchanging zone of the lung. They are lined by the typical respiratory epithelium with ciliated cells and numerous interspersed mucus-secreting goblet cells. Ciliated cells are present far down in the airway tree, their height decreasing with the narrowing of the tubes, as does the frequency of goblet cells. In bronchioles the goblet cells are completely replaced by another type of secretory cells named Clara cells. The epithelium is covered by a layer of low-viscosity fluid, within which the cilia exert a synchronized, rhythmic beat directed outward. In larger airways, this fluid layer is topped by a blanket of mucus of high viscosity. The mucus layer is dragged along by the ciliary action and carries the intercepted particles toward the pharynx, where they are swallowed. This design can be compared to a conveyor belt for particles, and indeed the mechanism is referred to as the mucociliary escalator. TMA INTERVIEW QUESTIONS&ANSWERS Academic year 2023 BRITANNICA QUIZ The Human Body You may know that the human brain is composed of two halves, but what fraction of the human body is made up of blood? Learn this fact and much more as you test both halves of your mind in this human anatomy quiz. Whereas cartilage rings or plates provide support for the walls of the trachea and bronchi, the walls of the bronchioles, devoid of cartilage, gain their stability from their structural integration into the gas-exchanging tissues. The last purely conductive airway generations in the lung are the terminal bronchioles. Distally, the airway structure is greatly altered by the appearance of cuplike outpouchings from the walls. These form minute air chambers and represent the first gas-exchanging alveoli on the airway path. In the alveoli, the respiratory epithelium gives way to a very flat lining layer that permits the formation of a thin air–blood barrier. After several generations TMA INTERVIEW QUESTIONS&ANSWERS Academic year 2023 (Z) of such respiratory bronchioles, the alveoli are so densely packed along the airway that an airway wall proper is missing; the airway consists of alveolar ducts. The final generations of the airway tree end blindly in the alveolar sacs. The lungs Gross anatomy The lung is parted into two slightly unequal portions, a left lung and a right lung, which occupy most of the intrathoracic space. The space between them is filled by the mediastinum, which corresponds to a connective tissue space containing the heart, major blood vessels, the trachea with the stem bronchi, the esophagus, and the thymus gland. The right lung represents 56 percent of the total lung volume and is composed of three lobes, a superior, middle, and inferior lobe, separated from each other by a deep horizontal and an oblique fissure. The left lung, smaller in volume because of the asymmetrical position of the heart, has only two lobes separated by an oblique fissure. In the thorax, the two lungs rest with their bases on the diaphragm, while their apexes extend above the first rib. Medially, they are connected with the mediastinum at the hilum, a circumscribed area where airways, blood and lymphatic vessels, and nerves enter or leave the lungs. The inside of the thoracic cavities and the lung surface are covered with serous membranes, respectively the parietal pleura and the visceral pleura, which are in direct continuity at the hilum. Depending on the subjacent structures, the parietal pleura can be subdivided into three portions: the mediastinal, costal, and diaphragmatic pleurae. The lung surfaces facing these pleural areas are named accordingly, since the shape of the lungs is determined by the shape of the pleural cavities. Because of the presence of pleural recesses, which form a kind of reserve space, the pleural cavity is larger than the lung volume. During inspiration, the recesses are partly opened by the expanding lung, thus allowing the lung to increase in volume. Although the hilum is the only place where the lungs are secured to surrounding structures, the lungs are maintained in close apposition to the thoracic wall by a negative pressure between visceral and parietal pleurae. A thin film of extracellular fluid between the pleurae enables the lungs to move smoothly along the walls of the cavity during breathing. If the serous membranes become inflamed (pleurisy), respiratory movements can be painful. If air enters a pleural cavity (pneumothorax), the lung immediately collapses owing to its inherent elastic properties, and breathing is abolished on this side. Pulmonary segments The lung lobes are subdivided into smaller units, the pulmonary segments. There are 10 segments in the right lung and, depending on the classification, eight to 10 segments in the left lung. Unlike the lobes, the pulmonary segments are not delimited from each other by fissures but by thin membranes of connective tissue containing veins and lymphatics; the arterial supply follows the segmental bronchi. These anatomical features are important because pathological processes may be limited to discrete units, and the surgeon can remove single diseased segments instead of whole lobes. The intrapulmonary conducting airways: bronchi and bronchioles TMA INTERVIEW QUESTIONS&ANSWERS Academic year 2023 In the intrapulmonary bronchi, the cartilage rings of the stem bronchi are replaced by irregular cartilage plates; furthermore, a layer of smooth muscle is added between the mucosa and the fibrocartilaginous tunic. The bronchi are ensheathed by a layer of loose connective tissue that is continuous with the other connective tissue elements of the lung and hence is part of the fibrous skeleton spanning the lung from the hilum to the pleural sac. This outer fibrous layer contains, besides lymphatics and nerves, small bronchial vessels to supply the bronchial wall with blood from the systemic circulation. Bronchioles are small conducting airways ranging in diameter from three to less than one millimetre. The walls of the bronchioles lack cartilage and seromucous glands. Their lumen is lined by a simple cuboidal epithelium with ciliated cells and Clara cells, which produce a chemically ill-defined secretion. The bronchiolar wall also contains a well-developed layer of smooth muscle cells, capable of narrowing the airway. Abnormal spasms of this musculature cause the clinical symptoms of bronchial asthma. The gas-exchange region The gas-exchange region comprises three compartments: air, blood, and tissue. Whereas air and blood are continuously replenished, the function of the tissue compartment is twofold: it provides the stable supporting framework for the air and blood compartments, and it allows them to come into close contact with each other (thereby facilitating gas exchange) while keeping them strictly confined. The respiratory gases diffuse from air to blood, and vice versa, through the 140 square metres of internal surface area of the tissue compartment. The gas-exchange tissue proper is called the pulmonary parenchyma, while the supplying structures, conductive airways, lymphatics, and non-capillary blood vessels belong to the non- parenchyma. The gas-exchange region begins with the alveoli of the first generation of respiratory bronchioles. Distally, the frequency of alveolar outpocketings increases rapidly, until after two to four generations of respiratory bronchioles, the whole wall is formed by alveoli. The airways are then called alveolar ducts and, in the last generation, alveolar sacs. On average, an adult human lung has about 480 million alveoli. They are polyhedral structures, with a diameter of about 250 to 300 µm (1 µm = 0.000039 inch), and open on one side, where they connect to the airway. The alveolar wall, called the interalveolar septum, is common to two adjacent alveoli. It contains a dense network of capillaries, the smallest of the blood vessels, and a skeleton of connective tissue fibres. The fibre system is interwoven with the capillaries and particularly reinforced at the alveolar entrance rings. The capillaries are lined by flat endothelial cells with thin cytoplasmic extensions. The interalveolar septum is covered on both sides by the alveolar epithelial cells. A thin, squamous cell type, the type I pneumocyte, covers between 92 and 95 percent of the gas-exchange surface; a second, more cuboidal cell type, the type II pneumocyte, covers the remaining surface. The type I cells form, together with the endothelial cells, the thin air–blood barrier for gas exchange; the type II cells are secretory cells. Type II pneumocytes produce a surface-tension-reducing material, the pulmonary surfactant, which spreads on the alveolar surface and prevents the tiny alveolar spaces from collapsing. Before it is released into the airspaces, pulmonary surfactant is stored in the type II cells in the form of lamellar bodies. These granules are the conspicuous ultrastructural features of this cell type. On top of the epithelium, alveolar macrophages creep around within the surfactant fluid. They are large cells, and their cell bodies abound in TMA INTERVIEW QUESTIONS&ANSWERS Academic year 2023 granules of various content, partly foreign material that may have reached the alveoli, or cell debris originating from cell damage or normal cell death. Ultimately, the alveolar macrophages are derived from the bone marrow, and their task is to keep the air–blood barrier clean and unobstructed. The tissue space between the endothelium of the capillaries and the epithelial lining is occupied by the interstitium. It contains connective tissue and interstitial fluid. The connective tissue comprises a system of fibres, amorphous ground substance, and cells (mainly fibroblasts), which seem to be endowed with contractile properties. The fibroblasts are thought to control capillary blood flow or, alternatively, to prevent the accumulation of extracellular fluid in the interalveolar septa. If for some reason the delicate fluid balance of the pulmonary tissues is impaired, an excess of fluid accumulates in the lung tissue and within the airspaces. This pathological condition is called pulmonary edema. As a consequence, the respiratory gases must diffuse across longer distances, and proper functioning of the lung is severely jeopardized. Blood vessels, lymphatic vessels, and nerves With respect to blood circulation, the lung is a complex organ. It has two distinct though not completely separate vascular systems: a low-pressure pulmonary system and a high-pressure bronchial system. The pulmonary (or lesser) circulation is responsible for supplying oxygen to the tissues of the body. Blood, low in oxygen content but laden with carbon dioxide, is carried from the right heart through the pulmonary arteries to the lungs. On each side, the pulmonary artery enters the lung in the company of the stem bronchus and then divides rapidly, following relatively closely the course of the dividing airway tree. After numerous divisions, small arteries accompany the alveolar ducts and split up into the alveolar capillary networks. Because intravascular pressure determines the arterial wall structure, the pulmonary arteries, which have on average a pressure five times lower than systemic arteries, are much flimsier than systemic arteries of corresponding size. The oxygenated blood from the capillaries is collected by venules and drained into small veins. These do not accompany the airways and arteries but run separately in narrow strips of connective tissue delimiting small lobules. The interlobular veins then converge on the intersegmental septa. Finally, near the hilum the veins merge into large venous vessels that follow the course of the bronchi. Generally, four pulmonary veins drain blood from the lung and deliver it to the left atrium of the heart. The bronchial circulation has a nutritional function for the walls of the larger airways and pulmonary vessels. The bronchial arteries originate from the aorta or from an intercostal artery. They are small vessels and generally do not reach as far into the periphery as the conducting airways. With a few exceptions, they end several generations short of the terminal bronchioles. They split up into capillaries surrounding the walls of bronchi and vessels and also supply adjacent airspaces. Most of their blood is naturally collected by pulmonary veins. Small bronchial veins exist, however; they originate from the peribronchial venous plexuses and drain the blood through the hilum into the azygos and hemiazygos veins of the posterior thoracic wall. The lymph is drained from the lung through two distinct but interconnected sets of lymphatic vessels. The superficial, subpleural lymphatic network collects the lymph from the peripheral mantle of lung tissue and drains it partly along the veins toward the hilum. The deep lymphatic system originates around the conductive airways and TMA INTERVIEW QUESTIONS&ANSWERS Academic year 2023 arteries and converges into vessels that mostly follow the bronchi and arterial vessels into the mediastinum. Within the lung and the mediastinum, lymph nodes exert their filtering action on the lymph before it is returned into the blood through the major lymphatic vessels, called bronchomediastinal trunks. Lymph drainage paths from the lung are complex. The precise knowledge of their course is clinically relevant, because malignant tumours of the lung spread via the lymphatics. The pleurae, the airways, and the vessels are innervated by afferent and efferent fibres of the autonomic nervous system. Parasympathetic nerve fibres from the vagus nerve (10th cranial nerve) and sympathetic branches of the sympathetic nerve trunk meet around the stem bronchi to form the pulmonary autonomic nerve plexus, which penetrates into the lung along the bronchial and vascular walls. The sympathetic fibres mediate a vasoconstrictive action in the pulmonary vascular bed and a secretomotor activity in the bronchial glands. The parasympathetic fibres stimulate bronchial constriction. Afferent fibres to the vagus nerve transmit information from stretch receptors, and those to the sympathetic centres carry sensory information (e.g., pain) from the bronchial mucosa vitamin, any of several organic substances that are necessary in small quantities for normal health and growth in higher forms of animal life. Vitamins are distinct in several ways from other biologically important compounds such as proteins, carbohydrates, and lipids. Although these latter substances also are indispensable for proper bodily functions, almost all of them can be synthesized by animals in adequate quantities. Vitamins, on the other hand, generally cannot be synthesized in amounts sufficient to meet bodily needs and therefore must be obtained from the diet or from some synthetic source. For this reason, vitamins are called essential nutrients. Vitamins also differ from the other biological compounds in that relatively small quantities are needed to complete their functions. In general these functions are of a catalytic or regulatory nature, facilitating or controlling vital chemical reactions in the body’s cells. If a vitamin is absent from the diet or is not properly absorbed by the body, a specific deficiency disease may develop. Vitamins are usually designated by selected letters of the alphabet, as in vitamin D or vitamin C, though they are also designated by chemical names, such as niacin and folic acid. Biochemists traditionally separate them into two groups, the water-soluble vitamins and the fat-soluble vitamins. The common and chemical names of vitamins of both groups, along with their main biological functions and deficiency symptoms, are listed in the table. The vitamins alternative symptoms of vitamin biological function names/forms deficiency Water-soluble component of a coenzyme in impairment of the nerves thiamin vitamin B1 carbohydrate metabolism; and heart muscle wasting supports normal nerve function TMA INTERVIEW QUESTIONS&ANSWERS Academic year 2023 The vitamins alternative symptoms of vitamin biological function names/forms deficiency Water-soluble component of coenzymes inflammation of the skin, required for energy production tongue, and lips; ocular riboflavin vitamin B2 and lipid, vitamin, mineral, and disturbances; nervous drug metabolism; antioxidant symptoms component of coenzymes used skin lesions, nicotinic acid, broadly in cellular metabolism, gastrointestinal niacin nicotinamide oxidation of fuel molecules, and disturbances, nervous fatty acid and steroid synthesis symptoms component of coenzymes in metabolism of amino acids and other nitrogen-containing dermatitis, mental pyridoxine, pyridoxal, vitamin B6 compounds; synthesis of depression, confusion, pyridoxamine hemoglobin, neurotransmitters; convulsions, anemia regulation of blood glucose levels impaired formation of red component of coenzymes in blood cells, weakness, DNA synthesis, metabolism of folate, folacin, irritability, headache, folic acid amino acids; required for cell pteroylglutamic acid palpitations, inflammation division, maturation of red of mouth, neural tube blood cells defects in fetus cofactor for enzymes in metabolism of amino acids smoothness of the tongue, (including folic acid) and fatty cobalamin, gastrointestinal vitamin B12 acids; required for new cell cyanocobalamin disturbances, nervous synthesis, normal blood symptoms formation, and neurological function as component of coenzyme A, weakness, gastrointestinal essential for metabolism of disturbances, nervous pantothenic carbohydrate, protein, and fat; symptoms, fatigue, sleep acid cofactor for elongation of fatty disturbances, restlessness, acids nausea cofactor in carbohydrate, fatty dermatitis, hair loss, biotin acid, and amino acid conjunctivitis, neurological metabolism symptoms swollen and bleeding gums, antioxidant; synthesis of soreness and stiffness of collagen, carnitine, amino acids, vitamin C ascorbic acid the joints and lower and hormones; immune extremities, bleeding under function; enhances absorption the skin and in deep tissues, TMA INTERVIEW QUESTIONS&ANSWERS Academic year 2023 The vitamins alternative symptoms of vitamin biological function names/forms deficiency Water-soluble of non-heme iron (from plant slow wound healing, foods) anemia Fat-soluble normal vision, integrity of ocular disturbances leading epithelial cells (mucous retinol, retinal, retinoic to blindness, growth membranes and skin), vitamin A acid, beta-carotene (plant retardation, dry skin, reproduction, embryonic version) diarrhea, vulnerability to development, growth, immune infection response calciferol, calatriol (1,25- dihydroxy vitamin D1 or maintenance of blood calcium defective bone growth in vitamin D hormone), vitamin D and phosphorus levels, proper children, soft bones in cholecalciferol (D3; plant mineralization of bones adults version), ergocalciferol (D2; animal version) antioxidant; interruption of free peripheral neuropathy, alpha-tocopherol, radical chain reactions; vitamin E breakdown of red blood tocopherol, tocotrienol protection of polyunsaturated cells fatty acids, cell membranes phylloquinone, synthesis of proteins involved in menaquinone, impaired clotting of the vitamin K blood coagulation and bone menadione, blood and internal bleeding metabolism naphthoquinone Biological significance of vitamins Discovery and original designation Some of the first evidence for the existence of vitamins emerged in the late 19th century with the work of Dutch physician and pathologist Christiaan Eijkman. In 1890 a nerve disease (polyneuritis) broke out among his laboratory chickens. He noticed that the disease was similar to the polyneuritis associated with the nutritional disorder beriberi. In 1897 he demonstrated that polyneuritis was caused by feeding the chickens a diet of polished white rice but that it disappeared when the animals were fed unpolished rice. In 1906–07 British biochemist Sir Frederick Gowland Hopkins observed that animals cannot synthesize certain amino acids and concluded that macronutrients and salts could not by themselves support growth. In 1912—the same year that Hopkins published his findings about the missing nutrients, which he described as “accessory” factors or substances—a Polish scientist, Casimir Funk, demonstrated that polyneuritis produced in pigeons fed on TMA INTERVIEW QUESTIONS&ANSWERS Academic year 2023 polished rice could be cured by supplementing the birds’ diet with a concentrate made from rice bran, a component of the outer husk that was removed from rice during polishing. Funk proposed that the polyneuritis arose because of a lack in the birds’ diet of a vital factor (now known to be thiamin) that could be found in rice bran. Funk believed that some human diseases, particularly beriberi, scurvy, and pellagra, also were caused by deficiencies of factors of the same chemical type. Because each of these factors had a nitrogen-containing component known as an amine, he called the compounds “vital amines,” a term that he later shortened to “vitamines.” The final e was dropped later when it was discovered that not all of the vitamins contain nitrogen and, therefore, not all are amines. In 1913 American researcher Elmer McCollum divided vitamins into two groups: “fat- soluble A” and “water-soluble B.” As claims for the discovery of other vitamins multiplied, researchers called the new substances C, D, and so on. Later it was realized that the water-soluble growth factor, vitamin B, was not a single entity but at least two—only one of which prevented polyneuritis in pigeons. The factor required by pigeons was called vitamin B1, and the other factor, essential for rats, was designated vitamin B2. As chemical structures of the vitamins became known, they were also given chemical names, e.g., thiamin for vitamin B1 and riboflavin for vitamin B2. Regulatory role The vitamins regulate reactions that occur in metabolism, in contrast to other dietary components known as macronutrients (e.g., fats, carbohydrates, proteins), which are the compounds utilized in the reactions regulated by the vitamins. Absence of a vitamin blocks one or more specific metabolic reactions in a cell and eventually may disrupt the metabolic balance within a cell and in the entire organism as well. With the exception of vitamin C (ascorbic acid), all of the water-soluble vitamins have a catalytic function; i.e., they act as coenzymes of enzymes that function in energy transfer or in the metabolism of fats, carbohydrates, and proteins. The metabolic importance of the water-soluble vitamins is reflected by their presence in most plant and animal tissues involved in metabolism. Some of the fat-soluble vitamins form part of the structure of biological membranes or assist in maintaining the integrity (and therefore, indirectly, the function) of membranes. Some fat-soluble vitamins also may function at the genetic level by controlling the synthesis of certain enzymes. Unlike the water-soluble ones, fat-soluble vitamins are necessary for specific functions in highly differentiated and specialized tissues; therefore, their distribution in nature tends to be more selective than that of the water-soluble vitamins. Sources Vitamins, which are found in all living organisms either because they are synthesized in the organism or are acquired from the environment, are not distributed equally throughout nature. Some are absent from certain tissues or species; for example, beta- carotene, which can be converted to vitamin A, is synthesized in plant tissues but not in animal tissues. On the other hand, vitamins A and D3 (cholecalciferol) occur only in animal tissues. Both plants and animals are important natural vitamin sources for human beings. Since vitamins are not distributed equally in foodstuffs, the more restricted the diet of an individual, the more likely it is that he will lack adequate amounts of one or more vitamins. Food sources of vitamin D are limited, but it can be TMA INTERVIEW QUESTIONS&ANSWERS Academic year 2023 synthesized in the skin through ultraviolet radiation (from the Sun); therefore, with adequate exposure to sunlight, the dietary intake of vitamin D is of little significance. All vitamins can be either synthesized or produced commercially from food sources and are available for human consumption in pharmaceutical preparations. Commercial processing of food (e.g., milling of grains) frequently destroys or removes considerable amounts of vitamins. In most such instances, however, the vitamins are replaced by chemical methods. Some foods are fortified with vitamins not normally present in them (e.g., vitamin D is added to milk). Loss of vitamins may also occur when food is cooked; for instance, heat destroys vitamin A, and water-soluble vitamins may be extracted from food to water and lost. Certain vitamins (e.g., B vitamins, vitamin K) can be synthesized by microorganisms normally present in the intestines of some animals; however, the microorganisms usually do not supply the host animal with an adequate quantity of a vitamin. Requirements in living things Vitamin requirements vary according to species, and the amount of a vitamin required by a specific organism is difficult to determine because of the numerous factors (e.g., genetic variation, relative proportions of other dietary constituents, environmental stresses). Although there is not uniform agreement concerning the human requirements of vitamins, recommended daily vitamin intakes are sufficiently high to account for individual variation and normal environmental stresses. A number of interrelationships exist among vitamins and between vitamins and other dietary constituents. The interactions may be synergistic (i.e., cooperative) or antagonistic, reflecting, for example, overlapping metabolic roles (of the B vitamins in particular), protective roles (e.g., vitamins A and E), or structural dependency (e.g., cobalt in the vitamin B12 molecule). Results of deficiencies TMA INTERVIEW QUESTIONS&ANSWERS Academic year 2023 vitamin deficiency Inadequate intake of a specific vitamin results in a characteristic deficiency disease (hypovitaminosis), the severity of which depends upon the degree of vitamin deprivation. Symptoms may be specific (e.g., functional night blindness of vitamin A deficiency) or nonspecific (e.g., loss of appetite, failure to grow). All symptoms for a specific deficiency disease may not appear; in addition, the nature of the symptoms may vary with the species. Some effects of vitamin deficiencies cannot be reversed by adding the vitamin to the diet, especially if damage to nonregenerative tissue (e.g., cornea of the eye, nerve tissue, calcified bone) has occurred. A vitamin deficiency may be primary (or dietary), in which case the dietary intake is lower than the normal requirement of the vitamin. A secondary (or conditioned) deficiency may occur (even though the dietary intake is adequate) if a preexisting disease or state of stress is present (e.g., malabsorption of food from the intestine, chronic alcoholism, repeated pregnancies and lactation). (More details on vitamin deficiencies in humans may be found in nutritional disease.) Evolution of vitamin-dependent organisms Evolution of metabolic processes in primitive forms of life required the development of enzyme systems to catalyze the complex sequences of chemical reactions involved in metabolism. In the beginning, the environment presumably could supply all the necessary compounds (including the vitamin coenzymes); eventually, these compounds were synthesized within an organism. As higher forms of life evolved, however, the ability to synthesize certain of these vitamin coenzymes was gradually lost. Since higher plants show no requirements for vitamins or other growth factors, it is assumed that they retain the ability to synthesize them. Among insects, however, niacin, thiamin, riboflavin, vitamin B6, vitamin C, and pantothenic acid are required by a few groups. All vertebrates, including humans, require dietary sources of vitamin A, vitamin D, thiamin, riboflavin, vitamin B6, and pantothenic acid; some vertebrates, particularly the more highly evolved ones, have additional requirements for other vitamins. The water-soluble vitamins Basic properties Although the vitamins included in this classification are all water-soluble, the degree to which they dissolve in water is variable. This property influences the route of absorption, their excretion, and their degree of tissue storage and distinguishes them from fat-soluble vitamins, which are handled and stored differently by the body. The active forms and the accepted nomenclature of individual vitamins in each vitamin group are given in the table. The water-soluble vitamins are vitamin C (ascorbic acid) and the B vitamins, which include thiamin (vitamin B1), riboflavin (vitamin B2), vitamin B6, niacin (nicotinic acid), vitamin B12, folic acid, pantothenic acid, and biotin. These relatively simple molecules contain the elements carbon, hydrogen, and oxygen; some also contain nitrogen, sulfur, or cobalt. The water-soluble vitamins, inactive in their so-called free states, must be activated to their coenzyme forms; addition of phosphate groups occurs in the activation of TMA INTERVIEW QUESTIONS&ANSWERS Academic year 2023 thiamin, riboflavin, and vitamin B6; a shift in structure activates biotin, and formation of a complex between the free vitamin and parts of other molecules is involved in the activation of niacin, pantothenic acid, folic acid, and vitamin B12. After an active coenzyme is formed, it must combine with the proper protein component (called an apoenzyme) before enzyme-catalyzed reactions can occur. Functions B-vitamin coenzymes in metabolism The B-vitamin coenzymes function in enzyme systems that transfer certain groups between molecules; as a result, specific proteins, fats, and carbohydrates are formed and may be utilized to produce body tissues or to store or release energy. The pantothenic acid coenzyme functions in the tricarboxylic acid cycle (also called the Krebs, or citric acid, cycle), which interconnects carbohydrate, fat, and protein metabolism; this coenzyme (coenzyme A) acts at the hub of these reactions and thus is an important molecule in controlling the interconversion of fats, proteins, and carbohydrates and their conversion into metabolic energy. Thiamin and vitamin B6 coenzymes control the conversion of carbohydrates and proteins respectively into metabolic energy during the citric acid cycle. Niacin and riboflavin coenzymes facilitate the transfer of hydrogen ions or electrons (negatively charged particles), which occurs during the reactions of the tricarboxylic acid cycle. All of these coenzymes also function in transfer reactions that are involved in the synthesis of structural compounds; these reactions are not part of the tricarboxylic acid cycle. Although vitamin C participates in some enzyme-catalyzed reactions, it has not yet been established that the vitamin is a coenzyme. Its function probably is related to its properties as a strong reducing agent (i.e., it readily gives electrons to other molecules). Metabolism TMA INTERVIEW QUESTIONS&ANSWERS Academic year 2023 The water-soluble vitamins are absorbed in the animal intestine, pass directly to the blood, and are carried to the tissues in which they will be utilized. Vitamin B12 requires a substance known as intrinsic factor in order to be absorbed. Some of the B vitamins can occur in forms that cannot be used by an animal. Most of the niacin in some cereal grains (wheat, corn, rice, barley, bran), for example, is bound to another substance, forming a complex called niacytin that cannot be absorbed in the animal intestine. Biotin can be bound by the protein avidin, which is found in raw egg white; this complex also cannot be absorbed or broken down by digestive-tract enzymes, and thus the biotin cannot be utilized. In animal products (e.g., meat), biotin, vitamin B6, and folic acid are bound to other molecules to form complexes or conjugated molecules; although none is active in the complex form, the three vitamins normally are released from the bound forms by the enzymes of the intestinal tract (for biotin and vitamin B6) or in the tissues (for folic acid) and thus can be utilized. The B vitamins are distributed in most metabolizing tissues of plants and animals. Water-soluble vitamins usually are excreted in the urine of humans. Thiamin, riboflavin, vitamin B6, vitamin C, pantothenic acid, and biotin appear in urine as free vitamins (rather than as coenzymes); however, little free niacin is excreted in the urine. Products (also called metabolites) that are formed during the metabolism of thiamin, niacin, and vitamin B6 also appear in the urine. Urinary metabolites of biotin, riboflavin, and pantothenic acid also are formed. Excretion of these vitamins (or their metabolites) is low when intake is sufficient for proper body function. If intake begins to exceed minimal requirements, excess vitamins are stored in the tissues. Tissue storage capacity is limited, however, and, as the tissues become saturated, the rate of excretion increases sharply. Unlike the other water-soluble vitamins, however, vitamin B12 is excreted solely in the feces. Some folic acid and biotin also are normally excreted in this way. Although fecal excretion of water-soluble vitamins (other than vitamin B12, folic acid, and biotin) occurs, their source probably is the intestinal bacteria that synthesize the vitamins, rather than vitamins that have been eaten and utilized by the animal. The water-soluble vitamins generally are not considered toxic if taken in excessive amounts. There is, however, one exception in humans: large amounts (50–100 mg; 1 mg = 0.001 gram) of niacin produce dilation of blood vessels; in larger amounts, the effects are more serious and may result in impaired liver function. Thiamin given to animals in amounts 100 times the requirement (i.e., about 100 mg) can cause death from respiratory failure. Therapeutic doses (100–500 mg) of thiamin have no known toxic effects in humans (except rare instances of anaphylactic shock in sensitive individuals). There is no known toxicity for any other B vitamins. The fat-soluble vitamins The four fat-soluble vitamin groups are A, D, E, and K; they are related structurally in that all have as a basic structural unit of the molecule a five-carbon isoprene segment, which is Each of the fat-soluble vitamin groups contains several related compounds that have biological activity. The active forms and the accepted nomenclature of individual TMA INTERVIEW QUESTIONS&ANSWERS Academic year 2023 vitamins in each vitamin group are given in the table. The potency of the active forms in each vitamin group varies, and not all of the active forms now known are available from dietary sources; i.e., some are produced synthetically. The characteristics of each fat-soluble vitamin group are discussed below. Chemical properties The chemical properties of fat-soluble vitamins determine their biological activities, functions, metabolism, and excretion. However, while the substances in each group of fat-soluble vitamins are related in structure, indicating that they share similar chemical properties, they do have important differences. These differences impart to the vitamins unique qualities, chemical and biological, that affect attributes ranging from the manner in which the vitamins are stored to the species in which they are active. Vitamin A group Ten carotenes, coloured molecules synthesized only in plants, show vitamin A activity; however, only the alpha- and beta-carotenes and cryptoxanthin are important to humans, and beta-carotene is the most active. Retinol (vitamin A alcohol) is considered the primary active form of the vitamin, although retinal, or vitamin A aldehyde, is the form involved in the visual process in the retina of the eye. A metabolite of retinol with high biological activity may be an even more direct active form than retinol. The ester form of retinol is the storage form of vitamin A; presumably, it must be converted to retinol before it is utilized. Retinoic acid is a short-lived product of retinol; only retinoic acid of the vitamin A group is not supplied by the diet. Vitamin D group Although about 10 compounds have vitamin D activity, the two most important ones are ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3). Vitamin D3 represents the dietary source, while vitamin D2 occurs in yeasts and fungi. Both can be formed from their respective provitamins by ultraviolet irradiation; in humans and other animals the provitamin (7-dehydrocholesterol), which is found in skin, can be converted by sunlight to vitamin D3 and thus is an important source of the vitamin. Both vitamin D2 and vitamin D3 can be utilized by rats and humans; however, chicks cannot use vitamin D2 effectively. The form of the vitamin probably active in humans is calcitriol. Vitamin E group The tocopherols are a closely related group of biologically active compounds that vary only in number and position of methyl (―CH3) groups in the molecule; however, these structural differences influence the biological activity of the various molecules. The active tocopherols are named in order of their potency; i.e., alpha-tocopherol is the most active. Some metabolites of alpha-tocopherol (such as alpha-tocopherolquinone and alphatocopheronolactone) have activity in some mammals (e.g., rats, rabbits); however, these metabolites do not support all the functions attributed to vitamin E. Vitamin K group TMA INTERVIEW QUESTIONS&ANSWERS Academic year 2023 Vitamin K1 (20), or phylloquinone, is synthesized by plants; the members of the vitamin K2 (30), or menaquinone, series are of microbial origin. Vitamin K2 (20) is the important form in mammalian tissue; all other forms are converted to K2 (20) from vitamin K3 (menadione). Since vitamin K3 does not accumulate in tissue, it does not furnish any dietary vitamin K. Functions The vitamin A group is essential for the maintenance of the linings of the body surfaces (e.g., skin, respiratory tract, cornea), for sperm formation, and for the proper functioning of the immune system. In the retina of the eye, retinal is combined with a protein called opsin; the complex molecules formed as a result of this combination and known as rhodopsin (or visual purple) are involved in dark vision. The vitamin D group is required for growth (especially bone growth or calcification). The vitamin E group also is necessary for normal animal growth; without vitamin E, animals are not fertile and develop abnormalities of the central nervous system, muscles, and organs (especially the liver). The vitamin K group is required for normal metabolism, including the conversion of food into cellular energy in certain biological membranes; vitamin K also is necessary for the proper clotting of blood. Metabolism The fat-soluble vitamins are transported primarily by lymph from the intestines to the circulating blood. Bile salts are required for efficient absorption of fat-soluble metabolites in the intestine; anything that interferes with fat absorption, therefore, also inhibits absorption of the fat-s

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