1 CAPE BIOLOGY UNIT TWO MANUAL (by Sperwin Zinger) MODULE ONE – BIOENERGETICS AND CONSERVATION THIS MODULE CONTAINS FOUR TOPICS: 1. PHOTOSYNTHESIS AND ATP SYNTHESIS 2. CELLULAR RESPIRATION AND ATP SYNTHESIS 3. ENERGY FLOW AND NUTRIENT CYCLING 4. ECOLOGICAL SYSTEMS, BIODIVERSITY AND CONSERVATIONS 2 TOPIC 1: PHOTOSYNTHESIS AND ATP SYNTHESIS 1.1: Relate the structure of a dicotyledonous leaf, a palisade cell and a chloroplast to their roles in the process of photosynthesis Photosynthesis is a process where AUTOTROPHS (or producers) take in inorganic molecules and produce organic substances, such as CARBOHYDRATES. These carbohydrates contain trapped energy that the organism can release and use from a molecule called ATP. Doing so is called RESPIRATION. ATP functions as the intracellular energy currency in all organisms. The name stands for adenosine triphosphate. It contains a nitrogenous base (adenine), a ribose sugar and three inorganic phosphate groups (Pi). When the bonds between these groups are broken, energy is released. First, a few basics about photosynthesis Firstly, recall that photosynthetic organisms contain CHLOROPLASTS (such as plants) or the lightcapturing pigment, CHLOROPHYLL, in membranes (such as phytoplankton). The word and chemical equations for photosynthesis in green plants can be written as: Photosynthesis involves a set of light-dependent and light-independent reactions. A basic outline of these reactions is depicted below. During the light-dependent stage, light energy is used to break the bonds of water molecules (a process called PHOTOLYSIS). OXYGEN diffuses out as a bi-product. The HYDROGEN molecules combine with CARBON DIOXIDE molecules, which are reduced to form GLUCOSE. REMEMBER: The light-dependent stage occurs in the THYLAKOIDS inside the chloroplast. The light-independent stage occurs in the „background material‟ of the chloroplast, called the STROMA. 3 THE DICOTYLEDONOUS LEAF (internal structure) Segment Description Function Upper epidermis Thin layer of transparent cells, usually coated with a watertight, waxy cuticle. Waxy cuticle limits water loss through the top of leaf; protects against insects and microbes; transparent to allow sunlight in. Lower epidermis Thin layer of cells interspersed with GUARD CELLS, which form stomata. Guard cells‟ unevenly thickened cell walls absorb water via osmosis and „curve‟ to open the stomata. This allows DIFFUSION and TRANSPIRATION to occur. Spongy mesophyll Loosely and irregularly packed layer of cells with numerous air spaces. Facilitates diffusion of materials and gaseous exchange between the palisade mesophyll and stomata. Palisade mesophyll Cylindrical cells arranged in an upright manner. They contain a large number of CHLOROPLASTS to facilitate light absorption. This type of packing creates several long, narrow air spaces. Contain a very LARGE VACUOLE so as to keep chloroplasts on the outer edges of the cells (to maximize exposure to light). They are also adjacent to VASCULAR BUNDLES, which supply water via the XYLEM. Contain very THIN CELL WALLS to facilitate efficient diffusion of gases. The chloroplasts are MOBILE due to proteins in the cytoplasm. A “palisade” is a fence, so think of the arrangement as such where there are ‘pickets’ with air-filled gaps between them with long, narrow areas of contact between the air and the cells. 4 THE CHLOROPLAST Chloroplasts are double-membraned organelles that contain inner membranes called LAMELLAE and sacs called THYLAKOIDS, which are then stacked to form GRANA. These are efficient at trapping light due to their large surface area. Thylakoid LUMENS aid in production of ATP by holding H+ ions. Within the chloroplast are photosynthetic pigments such as chlorophyll. Chlorophyll comes in two forms, chlorophyll a and chlorophyll b. Chlorophyll a and b are similar, but a absorbs slightly longer wavelengths of light. Leaves appear green because they absorb all colour wavelengths except green (which they reflect). Another pigment, CAROTENOIDS, tend to reflect red and orange instead. 1.2: Explain the process of photophosphorylation with respect to photosynthetic electron transport PHOTOPHOSPHORYLATION? PHOTOSYSTEMS? What is that? Let‟s break the word down: Photo (use of light), phosphorylation (adding a phosphate to a compound). The concept is, thus, simple: Photophosphorylation is a biochemical process that uses light to attach a phosphate group to an organic compound. ADP has two phosphates (diphosphate), while ATP has three (triphosphate). So photophosphorylation refers to the production of ATP from ADP (by adding a phosphate) using light energy. This energy enables an ELECTRON to move through a series of ELECTRON CARRIERS to form an ELECTRON TRANSPORT CHAIN in the chloroplast‟s thylakoids. Think of that electron as a ball in a pinball machine, zipping around, gradually losing energy. The initial energy to move this „ball‟ around comes from light particles (photons) being caught by an antenna complex in a PHOTOSYSTEM, which is a chlorophyll-protein complex in the chloroplast. There are two such systems, named PSI and PSII. In some circumstances, PSI generates ATP. It may also generate NADPH (or reduced NADP). NADPH is an electron donor and reducing agent necessary for photosynthesis. It is easy to confuse it with NAD, the coenzyme needed for respiration. Think of the “P” in NADP as a link to the word „Photosynthesis‟. A very important cofactor to make NAD and NADP is Vitamin B3. 5 CYCLIC AND NON-CYCLIC PHOTOPHOSPHORYLATION (Light-Dependent) Think of these as a series of steps in a metabolic pathway. The main goal is produce ATP from ADP, in light-dependent reactions. Both involve excited ELECTRONS that break loose from the chlorophyll a molecule when light hits them, which then pass through an ELECTRON TRANSPORT CHAIN (ETC). Let‟s define each one and then note the differences: Cyclic Photophosphorylation can be defined as the synthesis of ATP during the light reaction stage of photosynthesis, resulting to a „cyclic‟ movement of electrons to and from Photosystem I (PSI). The excited electron „returns‟ to the PSI chlorophyll, and the cycle restarts. This usually occurs in isolated chloroplasts and photosynthetic bacteria. Non-cyclic Photophosphorylation can be defined as the synthesis of ATP during the light reaction stage of photosynthesis in which an electron donor is required and oxygen is produced as a by-product. The excited electron passes from PSII to PSI. It then replaces any electron lost in PSI. Instead of PSI producing ATP here, the electrons reduce NADP to NADPH. This process may be the one more familiar to us, since this usually occurs in green plants. Factor Cyclic Non-cyclic Is ATP produced? Yes Yes Photosystems involved? PSI only PSI and PSII Is reduced NADP made? No Yes PSI replacement electrons found where? From the electron that it emitted itself From the electron emitted in PSII PSII replacement electrons found where? PSII is not involved in cyclic. From the photolysis of water. Predominates when? Anaerobic conditions Aerobic conditions Evolution of oxygen? No Yes KEEP IN MIND: Recall that ‘photolysis’ is the splitting of a water molecule to produce oxygen and hydrogen. H+ ions are released, which reduce NAPD. Electrons are emitted, which return to PSI. PROTON GRADIENT IN NON-CYCLIC PHOTOPHOSPHORYLATION 1. Water is split into H+ ions, O62 and electrons, which are released as they become “excited” by light. 2. As the electron passes from PSII to PSI, it stimulates the movement of H+ ions from the stroma to the thylakoid lumen. This establishes a proton gradient. Think of the electron as a ball in a pinball machine, bouncing off proteins and allowing reactions to occur, such as moving H+ ions or reducing NADP. These H+ are like the „final ingredient‟ for ATP in the ATP synthase „oven‟. 3. The proton gradient allows H+ ions to flow from the thylakoid to the stroma. These form ATP as the H+ pass through ATP synthase enzymes embedded in the membrane. 4. Finally, H+ ions and electrons reduce NADP to form NADPH. 1.3: Outline the essential stages of the Calvin cycle and light independent fixation of carbon dioxide; CALVIN CYCLE (Light-Independent) What were two products of photophosphorylation? Remember the goal was to produce ATP and noncyclic produces NADPH. And this all required light to excite electrons and occurred in the THYLAKOIDS. In the light-independent stage, the goal is to produce GLUCOSE and other carbohydrates. This occurs in the STROMA of the chloroplast, because in the stroma is a special enzyme called ribulose biphosphate carboxylase (referred to as RUBISCO from now on). Rubisco catalyses a reaction to combine carbon dioxide with a molecule called RuBP. This occurs in the CALVIN CYCLE, shown below. As you recall, glucose is a 6C sugar (hexose). RuBP is a 5C sugar (pentose), so it needs a carbon from CO2 to become a hexose. This doesn‟t occur all at once, and must first build some 3C sugars (triose). The entire purpose here is to create GLUCOSE (or fructose, sucrose, etc.) These sugars are made from the triose phosphate (or G3P), after the reduction of phosphoglyceric acid. G3P is a key phop molecule here, as it also helps re-initiate the cycle. CARBON FIXATION (Carboxylation) A CO2 molecule combines with the 5C RuBP, thanks to rubisco. This creates a 6C intermediate (not glucose), which then break down into two 3C acids (phosphoglyceric acid). REDUCTION ATP and NADPH are used to convert the 3C acids into G3P (triose phosphate). NADPH donates electrons to do this. G3P goes on to make GLUCOSE or even amino acids, if nitrogen is added. REGENERATION ATP is used to allow unused G3P molecules to be recycled back into RuBP to restart cycle. 7 So far, let‟s recap some key compounds we encountered. Compound Function NADPH Reduced NADP. A reducing agent for reactions, such as to form G3P. G3P (or triose phosphate) The first sugar made in photosynthesis, and helps to form sucrose and other carbs. These also help reform RuBP molecules to restart Calvin cycle. Formed after reduction of the compound, phosphoglyceric acid (or PGA) RuBP A 5C sugar in the chloroplast that will eventually take in CO2 to become a 6C and eventually lead to the formation of glucose. Rubisco The enzyme in plants that helps combine RuBP with CO2 (carboxylation). H+ ions Protons. Released during photolysis and helps to form ATP and NADPH. 1.4 & 1.5:Discuss the concept of limiting factors in photosynthesis; and discuss how knowledge of these can be applied to the improvement of plant productivity. What are LIMITING FACTORS OF PHOTOSYNTHESIS? You‟ll recall that photosynthesis requires the presence of the following: Energy in the form of sunlight Raw materials (carbon dioxide and water) A reasonable temperature (usually around 25-35oC) Chloroplasts and light-capturing pigments, such as chlorophyll The limitation of any of the above will also limit the rate of photosynthesis. For example, a green plant in a warm room supplied with carbon dioxide and water will photosynthesise at a high rate during the day outdoors; however, in a room with dim sunlight, the process will be very limited and occur at a slower rate. Thus, these are known as LIMITING FACTORS of photosynthesis. 8 Table representing limiting factors of photosynthesis: Limiting Factor Graph Explanation Light intensity In the light-dependent stage, light provides energy to excite ELECTRONS in chlorophyll reaction centres that eventually trigger reactions. Since there are only a finite number of chlorophyll molecules, light stops being a limiting factor at a certain intensity as all of them are already „firing‟. This is called the saturation point. Increasing light intensity after this point does not increase rate of photosynthesis. CO2 concentration Carbon dioxide is required in the chloroplasts to donate carbon atoms to RuBP to produce hexose sugars that eventually turn into glucose. Remember this is facilitated through the enzyme, RUBISCO. If CO2 concentration is limited, this Calvin Cycle process is slowed down, and rate of photosynthesis decreases. Same as light intensity, it reaches saturation at a certain concentration and plateaus. Temperature In Unit 1, we learned that enzymes are globular proteins that usually have tertiary structures. Their bonds can be broken if too much heat or kinetic energy is applied, causing the enzyme‟s structure to change, leading to DENATURATION. This can happen to rubisco, causing it to „malfunction‟ and instead waste RuBP by combining it with OXYGEN (photorespiration) severely decreasing photosynthetic rates. GREENHOUSES can have artificial light so that photosynthesis can continue beyond daylight hours, or at a higher than normal light intensity. The use of paraffin lamps inside a greenhouse increases the rate of photosynthesis because the burning paraffin produces carbon dioxide as well as heat. GROWTH CHAMBERS can also offer precise controls of environmental limiting factors such as temperature regulation and CO2 concentration for crops sensitive to fluctuating abiotic factors, such as groundnuts, or in areas prone to drought. HYDROPONICS are liquid-medium, soil-less systems that plants are sometimes grown in. Hydroponics allow the grower to optimize mineral ions given to plants. Mineral ions are required to synthesise other essential molecules from the glucose produced during photosynthesis. 9 TOPIC 2: CELLULAR RESPIRATION AND ATP SYNTHESIS 2.1: Explain the sequence of steps in glycolysis. What is GLYCOLYSIS? Glycolysis translates to „breaking apart of glucose‟. As glucose is broken down by enzymes in the CYTOSOL of cells, energy is released. This energy is used to make ATP, the currency of life necessary for metabolic processes. This breakdown of glucose occurs over a sequence of steps. Keep in mind this is a simplified depiction. Pay attention to the sections labelled 1 – 3. LABEL 1 . Glucose is first phosphorylated to form glucose-6phosphate by adding a phosphate. This uses 1 ATP. Glucose-6-P is isomerized to form Fructose-6-P. Fructose-6-P is phosphorylated to produce Fructose Biphosphate. This uses 1 ATP. LABEL 2 Fructose biphosphate is unstable and eventually undergoes LYSIS to become two 3C sugar molecules, one of them being G3P and the other being an isomer, DHAP, which rearranges to also become G3P. LABEL 3 Now we have two G3P molecules. These will eventually become a compound known as PYRUVATE. To do this, they must be oxidized with the help of a DEHYDROGENASE (hydrogen-removing) enzyme. Dehydrogenase functions if an enzyme helper (coenzyme) called NAD is present. NAD „receives‟ the hydrogen that the enzyme removes (imagine it like a catcher‟s mitt for H). It then reduces to form NADH. Both G3P‟s are oxidized to form two 3-carbon molecules of pyruvate. In the end, ADP molecules are converted to ATP. Some energy from the initial glucose molecule is transferred to these ATP molecules, a process called SUBSTRATELEVEL PHOSPHORYLATION Finally, 2 ADP are phosphorylated to form 2 ATP. This happens twice, so 2 NADH‟s and 4 ATP are made in the end here. Only 2 net ATP are gained as the first phase with glucose (Label 1) uses 2 ATP. 10 2.2: Describe the structure of a mitochondrion, relating its structure to its function The MITOCHONDRION – everyone‟s favourite „powerhouse‟ of the cell Recall that the goal of glycolysis was to break glucose down into a compound known as PYRUVATE. Pyruvate is responsible for RESPIRATION after it moves into the mitochondria. If OXYGEN is sufficient in the cytosol, it converts into Acetyl CoA and enters the Krebs cycle (discussed later) and AEROBIC respiration can occur. In the absence of oxygen, ANAEROBIC respiration occurs as pyruvate is broken down into ETHANOL or LACTATE. Observe the diagram and annotations of a mitochondrion cross-section below: Into the mitochondria: NADH ADP + Pi Pyruvate Oxygen Out of the mitochondria NAD ATP CO2 H2O For such a tiny organelle, there‟s a great amount of complex reactions occurring in the mitochondria. Much of the action occurs in the MATRIX, the fluid-filled space. ATP is made here due to the energy from the flow of hydrogen ions. The INNER MEMBRANE contains an enzyme called ATP synthase, that helps make ATP. It also contains carriers for electron transport chains that carry electron energy used to produce ATP. The CRISTAE are inward folds of this membrane. The more cristae present, the more active the mitochondrion due to increased amounts of ATP synthase. 11 2.3 – 2.5: State the fate of pyruvate in the cytosol when oxygen is available; explain the significance of the Krebs cycle in ATP production; and oxidative phosphorylation w.r.t. the electron transport chain Before we continue, there are going to be some new compounds and terms we‟re going to have to get acquainted (or re-acquainted) with: Compound / Term Description Pyruvate Product of glycolysis. Two are produced. Eventually converted to acetyl CoA. NAD A coenzyme. After accepting a hydrogen, it becomes NADH. Coenzyme A (CoA) Helps convert pyruvate to acetyl CoA. Also helps produce citrate. Acetyl CoA A 2C compound that acts as the „fuel‟ to keep the Krebs cycle going. Link reaction Process that forms carbon dioxide as pyruvate is converted to Acetyl CoA. Also called oxidative decarboxylation. Krebs cycle A series of reactions that generate ATP through the oxidation of acetate. Oxidative phosphorylation Process where ATP is formed. Occurs as a result of the transfer of electrons from NADH or FADH2 to O2. Electron transport chain (ETC) A cluster of proteins in the inner mitochondrial membrane that shuttle electrons and drives the creation of ATP and water during respiration. FAD Like NAD, but accepts two hydrogens to reduce to FADH2. KEEP IN MIND: You can think of NAD and FAD as ‘uncharged batteries’ that become charged after having accepted hydrogens to become reduced. NADH and FADH2 can then be reoxidized to make ATP molecules. Remember that this series of reactions represents the stages of AEROBIC respiration, where the inputs are glucose and oxygen and the products are carbon dioxide, water and ATP. Glycolysis converts 6C glucose into 3C pyruvate. The link reaction turns 3C pyruvate into 2C acetyl coA, needed for the Krebs cycle. A carbon leaves via creation of CO2. The Krebs cycle allows 2C acetyl coA to combine with 4C oxaloacetate to become 6C citrate, which initiates steps to oxidative phosphorylation, where ATP is formed. The ETC also drives ATP production but also helps create water. 12 What is THE LINK REACTION? The link reaction is named as such as it is the intermediate step that „links‟ glycolysis (which produces pyruvate) to the Krebs cycle (which produces ATP). Another name for it is oxidative decarboxylation (called that because carbon dioxide is removed during this process). Observe the diagram below. So, what is happening? You can see pyruvate (3C) is losing a carbon due to the removal of carbon dioxide. Hydrogens are removed as this occurs, which are captured by NAD to reduce it to NADH. An enzyme known as coenzyme A (or CoA) converts the 2C compound to Acetyl CoA (2C). If the Krebs cycle was a car, think of Acetyl CoA as the gasoline to keep it going! What is the infamous KREBS CYCLE? The Krebs cycle is a series of steps that occur within the MATRIX of the mitochondria. There are two main things that happen here: A 6C compound (citrate) is gradually turning into a 4C compound (oxaloacetate)... While ATP is being produced once per cycle (amongst other molecules that also help produce ATP). Remember Acetyl CoA? This is a 2C compound. With the help of coenzyme A once again, this combines with a 4C compound called oxaloacetate. This creates a 6C compound called citrate. Two carbon dioxides leave after some steps. Remember that as this happens, hydrogens are released as well. And what „catches‟ those? NAD! So each time, NAD is reduced to NADH. Since two CO2‟s leave, the 6C becomes a 5C, then a 4C. As other enzymes come into play, so does another coenzyme called FAD. FAD works like NAD. It accept hydrogens to reduce to FADH2, which can go on to form 1.5 ATP when reoxidized. (NADH yields 2.5 ATP) Eventually, the 4C compound becomes oxaloacetate once again, waiting to combine with Acetyl CoA (from the link reaction) to become citrate and restart the cycle. 13 So, to put the link reaction and the Krebs cycle step-by-step, so far: 3C pyruvate loses a CO2 to turn into 2C Acetyl CoA, with help from coenzyme A. When CO2 is removed, NAD accepts a hydrogen and reduces to NADH. 2C Acetyl CoA combines with 4C oxaloacetate to become 6C citrate. 6C citrate becomes a 4C compound after two CO2‟s are removed (which lead to two more hydrogens being accepted by NAD and two NADH‟s being formed). ATP is produced now. Only one ATP per cycle like this. This is substrate-level phosphorylation. As hydrogens are being lost from the 4C compound, FAD is reduced to FADH2. This cycle will then restart once the 4C compound becomes oxaloacetate again. FADH2 and NADH can yield ATP if they become FAD and NAD once again if they are oxidized (lose their hydrogens) again. This is called oxidative phosphorylation. What is OXIDATIVE PHOSPHORYLATION and the ELECTRON TRANSPORT CHAIN? Oxidative phosphorylation can be defined simply: the use of OXYGEN to attach a phosphate group (Pi) to ADP for it to become ATP. This is facilitated through an electron transport chain, a series of electron carriers and proteins. In the ETC, electrons are shuttled from one molecule to another. This releases energy. This energy is used to form an electrochemical gradient (more on this later) and used to make ATP. At the end of the ETC is OXYGEN. Think of oxygen completing a „circuit‟, so if oxygen isn‟t present, the entire chain is „broken‟ and stops working, so no ATP is made. Remember all those NADH‟s? They once were NAD‟s that caught a hydrogen and became reduced. When NADH oxidizes and releases this hydrogen (imagine the catcher‟s „tossing‟ out the H+ ion), it turns back into NAD. This NAD can then be returned to the Krebs cycle to be reused. The hydrogen atom splits into two components: a H+ ion (known as a „proton‟) and an electron (or e-). It is the electrons‟ journey that we‟ll observe. The electron is passed from carrier to carrier until it reaches the end of the chain, where there would be a molecule of OXYGEN. Now, remember that as each carrier loses the electron, it is oxidized and the subsequent carrier that gains the electron is reduced. The very act of this occurring is what releases energy needed to make ATP. When the electron reaches the OXYGEN at the end of the ETC, it combines with H+ ions to produce a WATER (H2O) molecule. 14 Now let‟s look at a bigger picture of what is happening and let‟s focus on labels 1 – 3: SIDENOTE: 34 molecules of ATP are made in glycolysis, link reaction and Krebs cycle. However, 2 ATP were used up during glycolysis. This means a net total of 32 ATP is made from one glucose molecule during aerobic respiration. Label What happens? 1 This is what was described on the previous page. Electrons from split hydrogens (from reduced NADs and FADs) are being shuttled from carrier to carrier along the ETC until they arrive at oxygen molecules, which help form WATER. This occurs in the mitochondrial MATRIX. 2 Recall that the electron contains energy! This energy is being used to pump H+ ions across channels along the inner membrane into the intermembrane space of the mitochondrion. These have a POSITIVE charge, of course, and create an ELECTROCHEMICAL GRADIENT between the matrix and intermembrane space, with the greater positive charge being in the intermembrane space. 3 H+ ions diffuse from a greater to lower „concentration‟ in a process called CHEMIOSMOSIS. However, this diffusion can only occur through channels which have ATPases (or ATP synthases) attached to them. ATPases are enzymes that help make ATP! So the energy from this diffusion of H+ ions helps convert ADP into ATP. Let‟s sum this up: 1. 2. 3. 4. Electrons from split hydrogen atoms contain energy and are shuttled along carriers in the ETC. Oxygen is the final receptor of the electron. The oxygen, the electron and H+ ions make water. This electron energy helps pump H+ ions through the inner membrane. This creates an electrochemical gradient, where the inner membrane has greater +ve charge than the matrix, as it now contains more H+ ions. 5. These H+ ions flow back down to the matrix but can only do so via special channels. 6. These channels have ATP synthases attached to them. The flow the H+ ions allows the enzyme to make ATP. 7. This process CANNOT occur without oxygen, as it is the final destination of the electron. 15 So how many ATP are produced from one molecule of glucose? Let‟s break it down! During oxidative phosphorylation, each NADH yields 2.5 ATP and each FADH2 yields 1.5 ATP. Glycolysis - Produces two pyruvate molecules. Produces two NADH‟s. (2 x 2.5 = 5 ATP) Produces 2 net ATP at substrate-level phosphorylation. Total = 7 ATP. Link reaction (decarboxylation) - Produces two NADH‟s, from the two pyruvates as they convert to acetyl coA‟s. Two NADH‟s = 2 x 2.5 = 5 ATP Krebs cycle - For both acetyl coA‟s, produces 6 NADH‟s and 2 FADH2‟s. For both acetyl coA‟s, produces 2 molecules of ATP at substrate-level phosphorylation. 6 NADH‟s = 6 x 2.5 = 15 ATP 2 FADH2‟s = 2 x 1.5 = 3 ATP Total = 15 + 3 + 2 = 20 ATP Total net ATP per glucose molecule = 7 + 5 + 20 = 32 ATP Total max ATP per glucose molecule = 32 ATP + 2 ATP (used during glycolysis) = 34 ATP Process Products formed Total ATP Glycolysis 2 ATP from substrate phosphorylation 2 NADH (5 ATP) 7 Link reaction 2 NADH (5 ATP) 5 Krebs cycle 6 NADH (15 ATP) 2 FADH2 (3 ATP) 2 ATP at substrate level phosphorylation 20 Totals 4 ATP from substrate-level, 10 NADH, 2 FADH2 32 16 2.6: Compare the fate of pyruvate in the absence of oxygen in animals and yeast. What happens during ANAEROBIC RESPIRATION and FERMENTATION? First of all, anaerobic respiration is the release of energy without the use of oxygen. Recall that without oxygen, the ETC cannot be „completed‟, and the ETC and oxidative phosphorylation is the final step of ATP production following the link reaction and Krebs cycle. Anaerobic respiration in humans There is, however, another metabolic pathway that can take place during GLYCOLYSIS to produce ATP. Remember that glycolysis breaks down glucose into a 3C compound called PYRUVATE. In humans, pyruvate can be converted to LACTATE (or lactic acid) in the absence of oxygen. In yeast, pyruvate is decarboxylated, releasing NOTE: In yeast, pyruvate is decarboxylated, releasing CO , to form ethanal before forming ethanol. 2 CO2, to form ethanal before forming ethanol. In the diagram shown, you can see that NAD (oxidized) and NADH (reduced) are in a „loop‟ to allow glycolysis to continue since the link reaction and Krebs cycle cannot be initiated without oxygen. This allows respiration to continue but only 2 net ATP is produced per glucose molecule (as opposed to 32 ATP during aerobic respiration). In YEAST, the above process is similar but two different products are yielded: ETHANOL and CO2. Ethanol is a major constituent of commercial alcohol, such as beer, rum and wine. In bread making, the CO2 is released from yeast causing dough to „rise‟. Lactobacillus bacteria can produce lactate to produce yoghurt and also help preserve grass feed for livestock. Also, the lactate that is produced builds up in the blood plasma of skeletal muscle cells, such as biceps and quadriceps. This can lead to painful CRAMPS. The lactate can also be taken in by the LIVER cells (hepatocytes) as they produce more pyruvate. When oxygen is supplied once again, the pyruvate can once again enter the link reaction and Krebs cycle. And that extra build-up of lactate in the liver can be „dissipated‟ by the oxygen, called an OXYGEN DEBT. So let‟s outline some differences between aerobic and anaerobic respiration: Aerobic Anaerobic Processes involved Glycolysis, link reaction, Krebs cycle, oxidative phosphorylation Glycolysis, fermentation. Decarboxylation of pyruvate to ethanal. Net ATP gained per glucose 32 2 Max ATP gained per glucose 34 4 Products formed Carbon dioxide and water Yeast – Ethanol and Carbon dioxide Bacteria and humans - Lactate 17 TOPIC 3: ENERGY FLOW AND NUTRIENT CYCLING 3.1: Discuss the efficiency of energy transfer between trophic levels; First of all, let‟s get re-familiarized with a few ecological terms: Term What happens? Habitat A place where an organism lives. Population A group of organisms of the same species, e.g. a group of snails. Community A group of organisms of multiple species, e.g. a group of snails, guppies and tadpoles. Niche The role an organism plays in its environment; its impact on the living and non-living factors. The collective dynamic of living (biotic) and non-living (abiotic) factors within an environment is known as an ECOSYSTEM. Most ecosystems are stable, unless there is some sort of external interference. These can include any of the following: The introduction of a disease-causing pathogen. A catastrophic shift in climate or weather, e.g. flash flooding or a hurricane. Human interference, such as urbanization, deforestation, poaching or noise pollution. The introduction of an invasive species, which can decimate a certain population. How is ENERGY transferred in an ecosystem? On the food chain shown, the grass is the PRODUCER (or autotroph, “self-feeding”), meaning that it can transform the electromagnetic energy from the Sun into stored chemical energy (carbohydrates) via the process of PHOTOSYNTHESIS. Some bacteria have this ability as well. Food chains and webs consist of TROPHIC levels, which represent levels of energy and feeding. In order, the trophic levels are: Producer Primary Consumer Secondary Consumer Tertiary Consumer Quaternary Consumer (or Apex Predator). Energy cannot be returned to the Sun, so it is referred to as an ENERGY FLOW as it moves from organism to organism as feeding occurs. Only an average of 10% of energy is transferred from one successive trophic level to another, which is why there is a limit of trophic levels. The energy obtained after quaternary consumers would be too little to sustain life in larger organisms. It is worth noting that certain consumers can occupy various trophic levels simultaneously, e.g. if the bluebird feeds on a fruit, it is also primary consumer. 18 Above, we observe the interlinking of multiple food chains. This is called a food web. It is important to note that the arrows in both chain and web point to the organism that does the feeding. High food web complexity is usually an indicator of high biodiversity and ecosystem stability. Observing such a food web, let‟s browse through a few scenarios: 1. A pathogen infects all of the aquatic vegetation (SAV). It is likely that all of the herbivorous ducks would die from starvation or migrate to another ecosystem that contains SAV (or other food from their diet). 2. Overfishing results in the removal of most of the large piscivorous fish. Since the large fish are the only source of food for the osprey, it would likely die or migrate. It is also likely that sea duck population would decrease as the bald eagle would lose a source of food. The small planktivorous fish population may increase initially, causing wading bird and gull population to also increase, and other „ripple effects‟ in the food chain. 3. An insecticide is dumped into the bay and assimilated into benthic invertebrates. Certain insecticides or pollutants can increase in concentration as they taken up into organisms with greater mass (biomagnification). The sea ducks and the bald eagle would become poisoned and potentially die, causing ripple effects in multiple other populations, such as bivalves, tundra swans, osprey and large piscivorous fish. 19 Energy „losses‟ across trophic levels It is important to remember that due to the law of conservation of energy, that energy cannot be „created nor destroyed‟. So energy is not actually „lost‟, but instead converted and transferred out of organisms due to metabolic processes. The simple energy flow diagram seen represents per 200 J of energy intake by a caterpillar. Only 10% of that figure (20 J) is left for energy storage in cells and only this amount can be directly transferred into the organism that consumes it (e.g. a bird). The other 180 J is transferred out into the ATMOSPHERE and to decomposers, usually as THERMAL energy released during respiration and excretion. You also have to take into account the following: - Not all parts of the organism is being consumed. Not all molecules consumed would be digested and assimilated, e.g. humans eating cellulose. Photosynthetic efficiency is another factor that has to be taken into account. Not all of the sunlight that enters the Earth‟s atmosphere is absorbed by plants. Leaves may have large surface areas but much of the sunlight will not be in contact with them. Energy is also „lost‟ when: Sunlight is reflected from leaf surfaces. Sunlight transmits through leaves and misses chlorophyll molecules. Certain ranges of wavelength cannot be absorbed by chlorophyll. Photosynthesis itself uses energy. What is GPP and NPP? If we imagine a leaf comes into contact with 100 units of solar energy, only about 40 of those units will be absorbed by chloroplasts and chlorophyll as stored chemical energy. The „lost‟ 60 units are reflected or miss the chloroplasts altogether. Of the 40 units that are actually absorbed, about 10 units is utilized for photosynthesis to make glucose. This is known as the leaf‟s GPP or GROSS PRIMARY PRODUCTIVITY. However, since energy is required for respiration to carry out the process of photosynthesis, even more energy is lost (about 4 units). So only about 6 units has been converted to sugars and stored as biomass out of that 100 that made contact with the leaf, and out of the 40 that was absorbed by chlorophyll. This 6 units is known as the NPP or NET PRIMARY PRODUCTIVITY. 20 3.2: Discuss the concept of biological pyramids. Pyramids of Numbers, Biomass and Energy Pyramids in the topic of ecology are ways to visually conceptualize information, similar to a bar graph or line graph. They usually sort information based on data collected from ecosystems with regards to population numbers and feeding relationships and sorts this data along trophic levels. Therein lies several limitations: 1. Population numbers are never static. They are dynamic or always changing, so collecting a true number of organisms is quite difficult, no matter the collection method (e.g. quadrats, transects, sweep nets, etc.). Organisms will have to be observed for a very long time in their habitats. 2. Organisms can occupy more than one trophic level simultaneously. 3. Feeding relationships may be affected by season or time of year. Nevertheless, pyramids are suitable for representing data on a large-scale basis. Let‟s see how this is done based on the table below, with regard to a PYRAMID OF NUMBERS, which simply represents the number of organisms that fall within each trophic level: Organism Feeding Number Bald eagle Cichlid Tiger Barb Phytoplankton Seaweed Grass carp Zooplankton Top Carnivore Carnivore Carnivore Producer Producer Herbivore Herbivore 3 80 40 8000 4000 200 2800 Trophic level total 3 120 12000 3000 Bear in mind that a pyramid of numbers may not have the typical „pyramid‟ shape, such as in a food chain that includes large producers such as trees or parasites within the organisms. This is because the pyramid does not take into the individual mass or size of each organism, only the counted number. A PYRAMID OF BIOMASS would account for the total mass of a population or trophic level occupying a certain area of the environment. Biomass is thus measured in g m-2. A single poui tree would have greater biomass than the entire ant population within it. 21 A PYRAMID OF ENERGY always has the typical pyramidal shape, like the pyramid of biomass. This is because it represents the flow of available energy from one trophic level to another. Recall that a large amount of energy is required to carry out metabolic processes in living organisms and only a 10% average may be stored in the cells, so at tertiary and quaternary trophic levels, the amount of energy becomes exponentially lower. A final summary of GPP, NPP and ENERGY LOSS Let‟s recap once more the definitions of GPP and NPP. Term Definition Gross Primary Productivity (GPP) The total quantity of useful chemical energy (in plant tissues) converted from energy from sunlight. Net Primary Productivity (NPP) The quantity of useful chemical energy converted from energy from sunlight AFTER RESPIRATION HAS TAKEN PLACE, thus: NPP = GPP – R. Various ecosystems will differ in NPP due to the area and type of vegetation and tree cover. For example, a desert will have a very low NPP due to the scarcity of green plants, while a tropical rainforest will have a very high NPP as it has a great amount of leaf cover to capture sunlight. Let‟s calculate the values for A, B and C in the chart shown: A: 20 810 − 11 977 = 8833 B: 1478 − 383 = 1095 C: 383 − 67 = 316 The GPP would be 20810 units, as that is how much the producers make from the sunlight. The NPP would be the GPP minus the respiration loss (11977), which would be 8833 units. 22 3.3: Describe how nitrogen is cycled within an ecosystem. Observe the diagram and table below with relation to THE NITROGEN CYCLE: Component Notes N2 (atmosphere) Nitrogen gas occupies 78% of the atmosphere. It has a triple covalent bond, making it unreactive in this state in both plants and animals. Nitrogen-fixing bacteria These „fix‟ N2 and convert the gas into a more reactive form, such as a nitrate or ammonium, using hydrogen and ATP in anaerobic conditions. The most common of this bacteria is RHIZOBIUM, which live in legume root nodules (e.g. peas). Lightning Nitrogen fixation can also occur in the atmosphere when lightning provides energy to combine nitrogen and oxygen to form nitrogen oxides. This can also be done synthetically by using the HABER PROCESS. Nitrifying bacteria Ammonium tends to be formed during decomposition (and decayed, fallen leaves) and as urea in animal urine. Nitrifying bacteria can convert this ammonium to a nitrite and then into a useable nitrate. Examples of this bacteria include Nitrosomonas and Nitrobacter. Nitrate (NO3-) Considered the type of nitrogen that a plant would absorb and assimilate into its cells to form larger molecules such as amino acids and nucleic acids. Denitrifying bacteria Does the reverse of nitrogen fixation, turning nitrates back into nitrogen gas and returns it to the atmosphere, thus restarting the cycle. 23 3.4: Explain how energy flow and nutrient cycling are important to ecosystems. How to distinguish between an ENERGY FLOW and a NUTRIENT CYCLE? Nutrients move within the ecosystem in biogeochemical cycles. A chemical element moves through the biotic and the abiotic components of an ecosystem. These include: carbon, hydrogen, oxygen, nitrogen and others, such as sulphur and phosphorus. These elements can be fixed into organisms, such as carbon being fixed into green plants during photosynthesis, or nitrogen into legume root nodules by Rhizobium. All of these cycles are driven by ENERGY FLOW. Energy flowing through the ecosystem originates from the Sun, which is captured by chlorophyll to make food. This food is then consumed by heterotrophs. Both autotrophs and heterotrophs eventually die and decompose. Decomposer bacteria and fungi allow nutrients from the cells of these organisms to return to an INORGANIC NUTRIENT POOL in the soil and atmosphere, ready to be taken up by plants once more. Energy flow is referred to as a „flow‟ as none of the energy is cycled (unlike nutrients). Energy does not return to its source (the Sun). During each step where biotic factors (producers, consumers and decomposers) are involved, HEAT is always transferred out to the atmosphere due to respiration and excretion. A note on decomposers It should also be noted that the removal of dead material can be done by numerous organisms, but decomposers are the only ones that break down dead organic matter into inorganic matter. Detritus feeders (or detritivores) are larger organisms, such as earthworms and maggots, digest and metabolize dead material. Even larger are carrion feeders (or scavengers), which eat large quantities of dead organic matter. These include vultures and hyenas. 24 TOPIC 4: ECOLOGICAL SYSTEMS, BIODIVERSITY & CONSERVATIONS 4.1: Discuss how ecosystems function as dynamic systems. BIOTIC AND ABIOTIC FACTORS Ecosystems are complex networks that consist of interactions between biotic and abiotic factors: Biotic factor Note Predation Where one organism hunts and eats another. This helps control several populations in the food web. Competition Where multiple organisms occupy similar niches and must vie for limited resources. Symbiotic relationships A relationship where at least one organism benefits. These include: Parasitism, where one benefits from harming the other (e.g. ticks and dogs) Commensalism, where one benefits while the other is unaffected (e.g. remora fish and shark) Mutualism, where both benefit (e.g. pea plants and Rhizobium) Altruism, where organisms cooperate for a common goal (e.g. ant colonies) Abiotic (non-living) factors include: Abiotic factor Note Light intensity Impacts the rate of photosynthesis and animal habits. Temperature Impacts the rate of evaporation and water supply; type of vegetation; and the metabolism of organisms; Gas concentrations O2 impacts rate of respiration and CO2 impacts rate of photosynthesis; on a larger scale, CO2 affects climate change and acidification of water biomes. pH Measurement of acidity or alkalinity of soil or water; impacts habitat. Soil characteristics Also known as edaphic factors. Soil aeration and soil pH affects subterranean life; particle size affects drainage; contains inorganic ions such as nitrates; soil pH affects type of terrestrial life and vegetation. Water characteristics Availability of water supply affects flora and fauna for sustenance and some for habitat; turbidity (muddiness) of water affects visibility; salinity and pH affects type of aquatic life. Wave action Helps with movement of nutrients and gases; continuous wave action can result in erosion or damage, e.g. to shorelines or coral reefs. Humidity High humidity decreases rates of evaporation and transpiration. Wind speed High wind speed increases rates of evaporation and transpiration. Topography The land‟s physical features, which impacts layout of habitats, and allows animals and vegetation to reside at multiple altitudes. 25 EXAMPLE OF AN ECOSYSTEM – The Aripo Savannah Scientific Reserve in Trinidad Left: Marshy area in Aripo Savannah; Middle: Student (J. Awong) in open savannah Right: (Top) A parasitic Cassytha vine. (Bottom) A carnivorous sundew plant (Drosera capillaris) For the CAPE Unit 2 syllabus, you are required to describe a model ecosystem. In this manual, that ecosystem will be the Aripo Scientific Reserve. The Aripo Reserve is situated has contains numerous biomes, including an open savannah and a marsh forest. In the savannah, the topography is very flat with small depressions caused by the burrowing of earthworms and termites. Since it is situated in a tropical climate, there is a high annual rainfall average of 2500mm, a stable medium-high temperature of 20 – 25oC, and a high humidity more than 50%. Since the open savannah has a constant high wind speed, it promotes rapid evaporation and transpiration in the plants. Grass growth is sparse in areas of acidic pH caused by domestic runoff. Since the soil mostly consists of low-drainage clay and has an impermeable clay layer at the surface, the land becomes easily flooded during the rainy season. The small depressions act as irrigation channels, which lead to soil becoming very dry, leading to water supply shortages to plants. Plants, as a result, have adapted to have XEROPHYTIC characteristics, such as reduced leaves and succulent tissues to retain water. Some of their roots have bulbs that store water. They also have stilted roots to keep them anchored during flooding. In terms of biotic factors, the Aripo Reserve contains over 250 species of plants, including many grasses, shrubs, mosses, orchids and tall woody trees. These plants exhibit numerous facets of symbiosis. Parasitic orange love vines (Cassytha) lack chlorophyll and thus must sap nutrients from other plants, harming them. Commensalistic epiphytes grow atop the woody trees to obtain sunlight. A common example of mutualism would be the nitrogen-fixing Rhizobium bacteria that live in the nodules of leguminous plants. Carnivory is observed in sundew plants, which trap and digest insects. Fauna in the Aripo Reserve include grass mice, agouti, opossum, numerous birds, insects and reptiles, such as iguanas, frogs and lizards. These exhibit typical feeding relationships. Human interference in the Reserve include squatting, quarrying, agricultural and industrial runoff, poachers setting fires, and illegal removal of timber from Galba trees and cocorite palms. 26 4.2 – 4.4: Explain the concept of biodiversity & discuss the importance of the maintenance of biodiversity; and how species diversity is related to ecosystem stability How does one define BIODIVERSITY? Biodiversity is a difficult factor to quantify, but we can think of it as being an amalgamation of three factors: 1. Species diversity 2. Genetic diversity 3. Ecosystem diversity Species diversity refers to the variety of different species found within a biome. For example, it can refer to the members of communities in a pond, such as different species of algae, weeds, mosses, plankton, snails, small fishes, frogs and so on. Tropical regions tend to have a high species diversity due to the high rainfall, humidity and light intensity, which all result in high tree density. A limitation of species diversity, however, only accounts for presence of species, not abundance. Genetic diversity refers to the variation of genetic information within the populations. Great population numbers usually indicate high genetic diversity. Recall that having selective pressures, isolation mechanisms and high rates of outbreeding increase the size of the gene pool and number of favourable alleles (less deleterious alleles). As a result, a species is more likely to resist pathogens and negative environmental consequences, raising chances of survival. Recall Galapagos finches and peppered moths. Ecosystem diversity refers to the variations in ecosystems in a defined geographical area. For example, the Aripo Reserve consists of multiple ecosystems, including the open savannah, a palm marsh and a marsh forest. It is also held within a watershed that sits between the Aripo and Quare Rivers. Having all of these different biomes adjacent to each other encourages intermingling of species and a „choice‟ of abiotic factors that encourage survival. What impacts SPECIES DIVERSITY and ECOSYSTEM STABILITY? Ecosystem stability refers to the ecosystem‟s resilience and ability to return to a normal state after being negatively impacted. Think of it as an ecosystem overcoming „selective pressures‟. A good example would be a grassland being able to regrow most of its vegetation after a period of drought. It is said that HIGH SPECIES DIVERSITY increases ecosystem stability, as less species are prone to migrating from or becoming extinct in that ecosystem after a disturbance, such as a disease or catastrophe. More members of populations would be able to survive, especially if there is also HIGH GENETIC DIVERSITY among the individuals. As a result, perturbations in the food web should be minimal over time and chances are greater for a return to equilibrium. If a single species dies out or migrates, this could affect the entire food web and feeding relationships among many organisms in that ecosystem, making it unstable. 27 Why is it important to MAINTAIN BIODIVERSITY? It is important to maintain biodiversity for a number of reasons; intrinsic (ethical or existence values), direct (known economic use) and indirect (unknown economic use). These include: Reason Notes Ecological stability (intrinsic) Discussed on previous page. Maintaining a high species diversity will promote greater chances of ecological recovery after negative impacts. Protecting endemic species (intrinsic) Certain species can only be found in single locations (endemic), such as the pawi and El Tucuche golden tree frog in Trinidad. If these or their habitats are not protected, they will go extinct. Tourism Coral reefs, safaris and nature trails tend to attract tourists from which countries earn revenue.. Money can be made from nature tours. (direct) Aesthetic (intrinsic) Nature itself is a source of relaxation and beauty for visitors. Many people take joy in knowing that various species simply exist in their natural habitats. Scientific value and research (indirect) Researchers tend to observe ecosystems and organisms as models for medicine and technology. Velcro was modelled after burrs sticking to clothing; Trinidad guppies and Anolis lizards are frequently observed as evolution models; and certain antibiotics have been extracted from tropical fungi; genes from daffodils were spliced into rice plants to make Vitamin A-rich Golden Rice. Raw materials (direct) By having good preservation and restorative practices (such as reafforestation), raw materials such as timber can be easily obtained without great disturbances to habitat. Flood prevention (indirect) Removal of trees and vegetation leaves soils exposed and waterlogged after periods of rainfall. This can lead to floods and soil erosion, further decimating habitats and depriving man of natural resources. Bequest value (intrinsic) When a generation places importance on preserving biodiversity so that future generations may be able to experience it. 28 4.5: Explain how in situ and ex situ conservation methods are used to maintain biodiversity. What is CONSERVATION? Conservation is the discipline of maintaining diversity by protecting species and their habitats, as well as ecosystems and biomes. There are two types: In situ conservation means conservation which takes place on-site. The major aim of this type of conservation is to preserve natural habitats of the organisms and maintain their number. This type of conservation includes designation, managing and supervise the target species. Examples include: National parks (e.g. Yosemite and Sequioa) Wildlife reserves and sanctuaries (e.g. Aripo) In situ conservation Ex situ conservation Ex situ conservation means conservation which takes place off-site. In this method of conservation, sampling, shifting, storage and preservation of target species is carried out outside the natural habitat of the organisms. Examples include: Zoos Botanic Gardens Seed banks and pollen storage In vitro storage for sperm & embryos Captive breeding programmes Here is a rundown of comparisons for both types of conservation: In situ Ex situ Involves natural habitats, so it is cheaper and allows for the process of adaptation and evolution. Usually used when natural habitats have been destroyed, or species has been in rapid decline. Usually does not have any issues with breeding or reproduction, though inbreeding may be possible with plants. Since organisms are in man-controlled environments, abiotic factors such as light intensity and temperature may affect courtship behaviours if not regulated, e.g. for seasonal organisms. No technology utilized for medical aid, organism health or to maximize reproductive success. Organisms can have long lifespans due to access to medical aid and security. Requires large areas of space. Requires smaller areas, though this may affect organism behaviour. 29 MODULE TWO – BIOSYSTEMS MAINTENANCE THIS MODULE CONTAINS SIX TOPICS: 1. THE UPTAKE AND TRANSPORT OF WATER AND MINERALS 2. TRANSPORT IN THE PHLOEM 3. THE CIRCULATORY SYSTEM OF MAMMALS 4. HOMEOSTASIS AND HORMONAL ACTION 5. THE KIDNEY, EXCRETION AND OSMOREGULATION 6. NERVOUS COORDINATION 30 TOPIC 1: THE UPTAKE AND TRANSPORT OF WATER AND MINERALS 1.1 & 1.2: Explain the uptake of ions by active transport in roots & describe the entry of water into plant roots in terms of water potential. What is TRANSPIRATION? Transpiration is simply defined as the movement of water through a plant and evaporation through its above-ground parts, such as the stomata of leaves. Inorganic ions such as nitrates and magnesium (for growth and chlorophyll production) are also taken up by the roots along with water molecules. While water is taken up through osmosis, inorganic ions are taken up into the cytoplasm from the soil through active transport or facilitated diffusion. If you recall from Unit 1, facilitated diffusion is a passive method of transport, meaning that it requires no ATP. Molecules move from regions of higher to lower concentration across channel proteins. Active transport moves molecules from regions of lower to higher concentration. This requires ATP to allow the carrier proteins to work to transport the ions across. This usually happens through the endodermis of the root, as this layer contains many carrier proteins. Water moves into the root hairs from the soil via osmosis. The water then moves from cell to cell along the permeable cell walls (the apoplast pathway) or through the cytoplasm (the symplast pathway). More on that later. The water (and dissolved ions) is then moved to the centre of the root, where xylem vessels are stacked end to end, going up the stem. From there, water is transported up the stem to the leaves. Along the way, it is absorbed by cells that need it. Excess water then leaves the stomata as vapour. All of this occurs because there is a gradually decreasing water potential gradient from the roots to the atmosphere, facilitating osmosis and water flow up the plant. However, there are numerous abiotic factors that affect this process, such as humidity. Root hairs increase the surface area of the roots, increasing the rates of both these processes. 31 What are the APOPLAST and SYMPLAST pathways? NOTE: An easy way to remember this is water can either move “a”cross cell walls (apoplast) or “s”traight through cytoplasm (symplast). Water diffuses from cell to cell down a water potential gradient until it gets to the xylem vessels at the centre of the root. This can occur along two pathways, shown in the diagram and in the table below: Pathway Movement of water Extra notes Symplast Water enters the root cells by crossing the plasma membrane and moving from cell to cell across gaps in the cell walls, called plasmodesmata. Water can continue until it reaches the xylem once it keeps diffusing down the water potential gradient. Apoplast Water does not enter the cytoplasm of the root cells. It stays in the freely permeable cell walls, where it flows from cell to cell. Water cannot continue to the xylem, due to waterproof blockages in the endodermis called Casparian strips. From the endodermis, the water molecules switch to the symplast pathway to get to xylem. Another thing to note is the way active transport affects rate of osmosis in the endodermis. Recall that the endodermis is loaded with transport proteins for inorganic ions. As ions are actively transported from the endodermis to the xylem (4 to 5 in the diagram), it reduces the water potential in the xylem. This steepens the water potential gradient and facilitates faster movement of water molecules into the xylem from the endodermis. This contributes to a „force‟ that pushes the water into and along the xylem called ROOT PRESSURE. 32 1.3 & 1.4: Relate the structure of xylem vessels to their function & explain the ascent of water in plants. Transverse Section of Xylem Vessels What is the XYLEM? Xylem vessels consist of elements that were once alive. They are primarily used for the transport of water and dissolved inorganic ions from the roots to the leaves. They are made up of a rigid, dead polymer known as lignin, which is used as structural support. This lignin can have a number of arrangements, including annular (ring-like) and reticulated (web-like). Because they usually come in close bundles, this also helps with structural support. The xylem also has pits in its walls that allow flow of water to and from adjacent cells. The tubes themselves are devoid of cell material, allowing uninterrupted flow. How is ASCENT OF WATER through xylem facilitated? Xylem vessels allows upward unidirectional movement of water in bulk, known as mass flow, similar to a drinking straw. To facilitate this kind of mass flow, the following factors must assist: Longitudinal Section of Xylem Vessels Water is cohesive, meaning that the molecules easily bind with each other due to its dipole nature. Water is also adhesive, which means that it sticks easily to the xylem walls. This allows a process called CAPILLARITY. As water molecules move into the leaf and leaves the stomata as water vapour, there is a tiny „pull‟ that occurs as each molecule exits, pulling the transpiration stream higher and higher up the stem. This is known as TRANSPIRATIONAL PULL. The xylem vessels are very narrow and unsegmented (continuous) facilitating capillarity and „transpirational pull‟. As mentioned on the previous page, ROOT PRESSURE builds up in the endodermis as inorganic ions are actively transported into the xylem. This lowers the water potential in the xylem, allowing more water to enter via osmosis. If there is low humidity (low amounts of atmospheric water vapour) and high wind speed, water molecules will diffuse out of the stomata at a fast rate, allowing the transpirational stream to flow faster. 33 1.5: Discuss the impact of environmental factors on the rate of transpiration. How do STOMATA function? Stomata are tiny pores in the epidermis (usually lower) of a leaf that allow diffusion of water vapour (transpiration) and other gases. They are surrounded by guard cells and their shape and function are influenced by the turgidity of these guard cells. If the guard cells are turgid (due to water moving in due to a high K+ ion concentration), they swell in a curved way, which allows passage of water. If the guard cells are not filled, they become flaccid and no diffusion of water occurs. Some stomata are organized in large stomatal chambers (or sunken stomata). These are typically covered in hair to trap still air and moisture. These are usually found in xerophytic plants (plants that retain large amounts of water). Which FACTORS influence RATE OF TRANSPIRATION? Factor Notes Temperature More kinetic energy in the water molecules would lead to a faster flow of the transpirational stream, especially as rates of evaporation increase. Light intensity Some plants close stomata at night (as they cannot photosynthesize at night), so water molecules cannot escape during that time. Humidity High humidity reduces transpirational rates, as it reduces the water potential gradient between the atmosphere and leaf. Low humidity increases transpiration. Air movements If there is moderate to high humidity, wind can allow pockets of air saturated with water vapour to move away from the stomata, steepening the water potential gradient. Plant anatomy Size and number of leaves; presence of hair on stomata; thickness of a waxy cuticle contribute to rate of transpiration. MEASUREMENT OF TRANSPIRATION RATES The set-up on the left is called a potometer, for measuring and comparing rate of transpiration. The starting position of the air bubble is marked. The air bubble moves towards the cut shoot as water is taken up. After a fixed amount of time, the final position of the bubble is marked, and a distance is determined. This distance will be short, for example, in a cold environment with no air movement. It will be longer in a warmer environment with high air movement. 34 TOPIC 2: TRANSPORT IN THE PHLOEM 2.1: Relate the structure of sieve tubes and companion cells to their function What is the PHLOEM? In Unit 1, the xylem and phloem were observed, discussed and drawn. The images above are a reminder of the placement of these tissues in dicotyledonous roots and stems. We learnt about the xylem in the last topic and its ability to help with transpiration, which is the movement of water and dissolved inorganic ions. The xylem is usually paired with another vessel called the PHLOEM. The phloem assists with the process of TRANSLOCATION, which is the transport of soluble organic substances such as sucrose. These are assimilated into cells for use. This transport occurs from photosynthetic organs (e.g. leaves) called sources to non-photosynthetic organs (e.g. roots) called sinks. The phloem consists of numerous sieve tube elements. These are elongated cells only have a few organelles, not even a nucleus or ribosomes, and very few mitochondria. This is why they are joined onto companion cells. Companion cells have a large concentration of mitochondria to supply ATP for „loading‟ and „unloading‟ assimilates into and out of cells through their plasmodesmata. Where two sieve tube elements meet, a sieve plate is formed. A sieve plate is a perforated disc with many sieve pores. Sieve plates facilitate mass flow through the phloem, and the pores may also reduce resistance by increasing the pressure through them. 35 Observe the micrographs of the phloem, & the table of comparisons between the xylem and phloem. Characteristic Xylem Phloem Function Transport of water and inorganic ions. Lignified walls are used for stem support. Transport of assimilates, such as sucrose and amino acids. Living or non-living? Non-living elements containing cellulose and lignin. Both sieve elements and companion cells are alive. However, the latter is more metabolically active. Segmented? Not segmented. Continuous. Segmented. Separated by sieve plates. Passive or active? Passive transport. No ATP. Active transport. Loading uses ATP. Direction of flow Unidirectional. Water flows from roots to leaves (transpiration). Bidirectional. Assimilates flow from source to sink, either up or down stem. 2.2: Explain how phloem loading in the leaves occurs against a concentration gradient What is a SOURCE and a SINK? Unlike the xylem, the phloem is bidirectional, meaning that flow can over either up or down the stem. This is determined by the location of sources and sinks. A SOURCE is any photosynthetic organ capable of producing sugars in excess, and able to transport it. Sucrose is unloaded from sources. An example is a mature leaf. A SINK is a non-photosynthetic organ that does not produce sugars but instead needs them to meet their own requirements. Sucrose is loaded into sinks. Examples include roots, tubers, nectaries, developing fruits and immature leaves. Sugars are transported in the form of sucrose as it is not as reactive as glucose and is more mobile than starch. It is transported by mass flow, like water in the xylem. 36 How does LOADING AND UNLOADING occur in the PHLOEM? It is important to first understand that translocation occurs due to hydrostatic pressure differences in the phloem. This occurs due to a combination of osmosis and active transport. Sucrose and ions are loaded onto the phloem from sources (e.g. leaves). This is usually done by active transport. H+ ions are pumped, using ATP, out of the companion cells, which creates a large concentration outside of the cell. As the H+ ions move back into the companion cell via a transport protein, they move into the sieve tube with sucrose. Think of this process as turning on a H+ ion „faucet‟ that pushes sucrose along with it. As the assimilates move into the phloem, the water potential decreases at that point. This facilitates osmosis of water from the xylem. As a result, the pressure from the incoming water pushes the assimilates down the phloem as mass flow. When the sucrose is unloaded from the phloem into sinks (e.g. roots), the water potential increases and so, water flows back into the xylem, where it flows up to the leaves again. 2.3: Discuss the mass (pressure) flow hypothesis as a possible mechanism of translocation. What EVIDENCE is there for mass flow in the phloem? Evidence that supports mass flow revolves around the concentration of H+ ions in the phloem sap and surrounding companion cells: 1. During mass flow, there is a great positive charge outside the companion cell and negative charge inside it. This is due to the large concentration of positively charged H+ ions outside the cell, creating an electrical gradient. 2. The pH of phloem sap is slightly alkaline before the influx of acidic H+ ions from the companion cell. As said, think of the H+ ions turning on a tap or faucet (the sucrose H+ co-transporter) that allows sucrose to flow from outside companion cells to phloem sieve tubes. The main argument against the mass flow hypothesis is that it does not account for bidirectional flow of sucrose, such as up the stem. For example, the flow of sucrose from mature leaves to immature leaves near the top of a plant. Another issue is that amino acids and sucrose flow at different rates in the phloem, something not possible with mass flow. 37 TOPIC 3: THE CIRCULATORY SYSTEM OF MAMMALS 3.1: Describe the structure of the heart, arteries, veins, capillaries, erythrocytes, and leucocytes, relating their structures to their functions What are the different parts of the MAMMALIAN HEART? The circulatory system is comprised of the heart, which acts as a pump; blood vessels, which act as a connected pipe network; and blood, which acts the transport medium. Only complex multicellular organisms require circulatory systems due to their high activity and metabolic levels, requiring a constant supply of oxygen and nutrients to cells and tissues for respiration. These types of organisms are said to exhibit a low surface area to volume ratio, unlike protozoans and insects. The structure of the human heart can be seen below, as well as descriptions of some main segments: NOTE: The right atrium has a small patch of muscle called the SAN (sino-atrial node), which initiates the cardiac cycle. More on that later. Segment Function Vena cava Carries deoxygenated from the body cells into the heart. Aorta Carries oxygenated blood away from the heart to the body cells. Pulmonary artery Carries deoxygenated blood away from the heart and to the lungs. Pulmonary vein Carries re-oxygenated blood to the heart back from the lungs. Valves Open and close to prevent backflow of blood. Septum Separates the left and right halves. Left ventricle Muscle-dense region of heart responsible for pumping blood to aorta. Use the acronyms: LORD (Left Oxygenated, Right Deoxygenated) T”R”icuspid (Right), MitraL (Left) Notable about the mammalian circulatory system is that it is considered a double circulatory system. What this means is that the blood enters and exits the heart twice per cycle: When the heart pumps to and receives blood from the lungs. (Pulmonary circulation) When the heart pumps to and receives blood from the body. (Systemic circulation) Blood always flows in a unidirectional manner through the chambers of the heart (the upper atria and lower ventricles). To facilitate this, valves are present. They prevent backflow. There are two types: atrioventricular (tricuspid and bicuspid/mitral) and semi-lunar (pulmonary and aortic). These synchronize to allow blood to flow in one direction. 38 What are the types of BLOOD VESSELS in the circulatory system? There are three main blood vessels in the circulatory system: arteries, veins and capillaries. Arteries and veins have muscular layers around them all prefixed tunica, with the tunica externa (outer), tunica media (middle) and tunica intima (inner, smooth endothelial tissue). Arteries are thick-walled vessels with small lumens. They always transport blood away from the heart to body cells. They have a thick tunica media, consisting of elastic fibres, and thick tunica externa, consisting of collagen. As a result, they are able to withstand high pressures. The main artery is the aorta. Coronary arteries supply the heart muscles with oxygen. Veins are thinner-walled vessels with large lumens that will collapse if blood were to stop flowing through them. They always transport blood towards the heart from the body cells. The main veins are the superior and inferior vena cava. Capillaries are very narrow blood vessels that surround tissues and organs. They have a single layer of endothelial cells that facilitate rapid diffusion. Red blood cells flow through these in single file. Characteristic Arteries Veins Direction of flow Away from heart. From cells to heart. Wall thickness Thicker (tunica media thicker than tunica externa) Thinner (tunica externa thicker than tunica media) Lumen diameter Smaller (about 0.7mm) Larger (larger than 1mm) Blood pressure Higher. Has a pulse. Lower. No pulse. Semi-lunar valves? No valves. Valves present. Oxygenated or deoxygenated? Oxygenated (except pulmonary) Deoxygenated (except pulmonary) Another note on CAPILLARIES While arteries and veins have elastic tissue and smooth muscles in their walls (the tunica layers), capillaries only have a single layer of endothelial cells. Most substances can diffuse though these cells but sometimes use exoand endocytosis to package them in vesicles. They only have a diameter of about 0.8µm, a little wider than an erythrocyte (red blood cell). They connect arterioles and venules in the capillary bed. Diagram showing longitudinal section of capillary 39 What are the types of BLOOD CELLS in the body? Blood is comprised of numerous cells, which makes it a tissue. These cells are transported via a yellow liquid known as plasma, consisting of proteins, and dissolved nutrients and nitrogenous waste products in water. Any cell that does not receive blood will eventually undergo necrosis (death). The cells include red blood cells (erythrocytes), white blood cells (leucocytes) and platelets (thrombocytes). In Module 3, the topic of Immunology delves more into leucocyte actions. The following are examples and images of these cells in the blood: Cell / Component Erythrocyte (red blood cell) Lymphocyte Neutrophils Monocytes and Macrophages Platelet (thrombocyte) Microscope Image Function Adaptations or Characteristics Has haemoglobin, which binds to oxygen and carbon dioxide for transport to and from cells. Has a biconcave shape, which allows rapid diffusion of gases. No major organelles (e.g. ER, mitochondria, nucleus), so more room for haemoglobin. Small in size (about 7µm) to fit through capillaries. Either makes antibodies (B-), sends signals (Thelpers) or kills infected cells (cytotoxic Tkillers) Has receptors on surfaces to bind antigens or toxins. Large round nuclei to store genetic data about antigens and instructions. Mature in either bone marrow (B-cells) or thymus (T-cells). All are produced in bone marrow. Engulfs pathogens and digests them. Able to „present‟ antigens to lymphocytes. Monocyte is a precursor to a macrophage. Comprises a small amount of white blood cells. Helps form blood clots to slow and stop bleeding as a response to injury. Large, multi-lobed nuclei. Granulated. Able to extend itself to create a pseudopodium („false foot‟) to move. Able to evaginate pathogens and package them in vesicles. Large, irregular nucleus. Very slightly granulated. Macrophages act similarly to neutrophils but are more involved in phagocytosis. They can „present‟ antigens as well. Small fragments that have broken off from bone marrow cells. Activates enzymes and clotting factors that eventually convert soluble fibrinogen in the plasma to insoluble fibrin, to eventually form a scab. 40 3.2 - 3: Explain the cardiac cycle & its initiation & discuss the internal factors that control heart action. What are the processes involved in the CARDIAC CYCLE? The cardiac cycle refers to the sequence of events that comprises one heartbeat. As we know, the heart has two „thumps‟ per beat, the second one „louder‟ than the other. These two events or „thumps‟ are referred to as Systole – Contraction of atria or ventricles, causing atrioventricular (AV) blood flow, or blood flow out of the heart (into the arteries). Think “S” in systole as „stress‟ or „squeezing‟ blood out. Diastole – Relaxation of atria and ventricles, allowing blood to flow into the heart to refill the chambers. Think “D” in diastole as the heart „dilating‟ or „de-stressing‟. This can be further broken down into these events, as shown on the table. Imagine the cycle starts when the upper chambers (atria) of the heart are already filled with blood: Event Description Atrial systole The atria contract. The vein valves close, preventing backflow into the veins. This carries blood from the atria to the ventricles. Ventricular systole The ventricles contract, pushing the blood into the aorta and pulmonary artery. The AV valves close, preventing backflow of blood into the atria. Ventricular diastole Both atria and ventricles relax, allowing blood to flow into the heart from the veins. Semi-lunar valves shut to prevent the blood from flowing „out‟. INITIATION OF THE CARDIAC CYCLE The SAN (or pacemaker) of the heart, located in the right atrium, is the site of initiation of the cardiac cycle. The SAN‟s muscle contracts and produces an electrical impulse, which propagates through the atria muscles, causing them to contract. This impulse then „activates‟ another node, called the AVN (atrioventricular node), which „relays‟ that impulse to the ventricles, causing them to contract. The process then repeats. Further detail on next page. Diagram NOTE: It is important to remember that all of the cardiac muscle cells must contract in unison during the cardiac cycle. A coordination centre called the pacemaker or SAN (sino-atrial node) or pacemaker helps this happen. This is the sequence of events for one cardiac 41 cycle: 1. The SAN is a myogenic muscle, which means it doesn‟t need an impulse to „initiate‟. sends out a wave of excitation across the nerves in the atria. 2. This causes the atria to contract. 3. The AVN picks up the signal and sends another wave of excitation to go to the ventricles. However, this wave experiences a „refractory period‟ or „delay‟ (about 0.3s) so that the atria and ventricles don‟t contract simultaneously. 4. Electrically excitable cells called Purkyne (or Purkinje) fibres conduct the signal from the AVN. They move into branches in the septum called Bundles of His. 5. The ventricles contract upon reception of signal. GRAPHICAL REPRESENTATION OF THE CARDIAC CYCLE NOTE: If the entire cycle on the left had been completed in 0.85s, how many heartbeats would there be per minute? Just divide 60s by 0.85s and you‟ll get approximately 70, which is the number of beats per minute for the average adult heart. Although the shape of the graph above is quite complex, there are only a few things we have to focus on. First of all, observe the periods of systole and diastole shown. You‟ll see that the pressure has a steep increase during ventricular systole, mostly due to the density of the cardiac muscle in the left ventricle. Recall that this pressure has to be high enough to pump blood through to the aorta to the arteries and body cells. This is why aortic pressure increases at this point as well. Also keep in mind that these valves (semi-lunar and AV) are open and closed due to changes in pressure. Note the pressure values 120/80 mm Hg. This is the typical systolic and diastolic pressure respectively. 42 Which FACTORS influence CARDIAC OUTPUT? Cardiac output is the volume of blood pumped out of the heart per minute. Think of it as a combination of heart rate (HR), which is the number of cycles per minute, and stroke volume (SV), which is the amount of blood pumped per cycle. Here are the factors that influence cardiac output: Factor Description O2 and CO2 concentrations Physical activity stimulates increased oxygenated blood flow. The oxygen deficiency in cells results in the release of nitric oxide. Nitric oxide dilates (widens) arterioles, allowing increased blood flow and cardiac output. High carbon dioxide concentrations can increase rate of heart beat, as well. These concentrations are detected by chemoreceptors in arteries. Parasympathetic During exercise, carotid (brain) artery walls may swell, stimulating baroreceptors („stretch‟ receptors) to send signals along the vagus nerve to the brain. This lowers nerves cardiac output to avoid overexertion. Sympathetic nerves Conversely, during exercise, sympathetic nerves will stimulate SAN and AVN to increase heart rate. Adrenaline Works the same as sympathetic nerves, except the hormone stimulates adrenoreceptors (hormonal receptors) to achieve the stimulatory effect on SAN and AVN. 3.4: Discuss factors affecting blood pressure. What FACTORS influence BLOOD PRESSURE? We would‟ve learned by now that blood pressure is influenced by cardiac output (which is influenced by nervous and hormonal activity), as well as blood vessel structure. Vessels with small lumens such as arteries have high pressures. If that lumen becomes smaller, such as due to the build-up of plaques (caused by „bad cholesterol‟), pressure becomes even higher. If diastolic pressure becomes persistently high, this condition is known as HYPERTENSION. Factor Explanation Exercise Explained above. Stimulation of nitric oxide allows increased blood flow. Cigarette smoking Tobacco contains nicotine, which constricts vessels and makes lumens smaller. They also contain nitric oxides. Adrenaline Explained above. Released during stress or excitement, which raises blood pressure. Atherosclerosis The accumulation of LDL‟s (low density lipoproteins) in arterial lumens reduces the area of the passageway for blood flow. Discussed further in Module 3. 43 3.5 – 3.7: Explain the role of haemoglobin in O2 and CO2 transport; describe oxygen dissociation curves for adult haemoglobin; and explain the significance of the effect of O2 on oxygen dissociation curves What is the role of HAEMOGLOBIN? Haemoglobin (Hb) is a protein found in red blood cells. It has a quaternary structure consisting of two alpha-chains and two-beta chains. These four sub-units each have prosthetic haem groups, each with an iron molecule. Each of these iron molecules can bind an oxygen molecule, meaning that up to four oxygen molecules can be bound by one haemoglobin molecule. When these oxygens are bound, it is now referred to as oxyhaemoglobin (HbO2). When oxygen is picked up in the lungs and transported to body cells, the oxygen is then „released‟ from the haemoglobin. It is said to have dissociated from it. Oxygen is faster picked up than carbon dioxide, so it is said to have a higher affinity for haemoglobin. Carbon monoxide from cigarette smoke and car exhaust has an extremely high affinity for haemoglobin, so much that it binds for dangerously prolonged periods of time (forming carboxyhaemoglobin) and prevents oxygen from binding. This most likely will result in asphyxiation and death. Carbon dioxide can also bind to haemoglobin, forming carbaminohaemoglobin. This only happens to 1/10th of CO2 in the blood. Also notable about haemoglobin molecules is that they exhibit a characteristic called positive cooperativity. This means that it may take a certain amount of oxygen concentration to bind one oxygen molecule, but as soon as that happens, there is a greater chance to bind the 2nd molecule, an even greater one for the 3rd and the greatest for the 4th. So haemoglobin takes the shortest time to bind the final oxygen molecule when it already has the other three bound to it. This is because haemoglobin experiences conformational changes (also known as an allosteric effect) with each successive binding of oxygen. The quaternary structure of the protein subtly changes to accommodate each new molecule. Think of the haemoglobin molecule as one of those blooming tea balls or compressed tissue towels that exponentially opens up more and more as it absorbs water. 44 OXYGEN DISSOCIATION CURVES Previously, we said that haemoglobin has a relatively high affinity for oxygen, meaning that oxygen molecules will readily bind the haem groups when placed together. However, this only occurs when the oxygen concentration is high enough. The main place where this binding occurs is in the alveoli. Since air is a mixture of various gases, this value of just oxygen concentration is referred to as a partial pressure. When partial pressures are high (such as in the alveoli), there is a greater percentage saturation of the haemoglobin (more O2 bound to haemoglobin). When partial pressures are low (such as in respiring muscle tissue), there is a lower percentage saturation of the haemoglobin. Keep in mind that oxygen levels in haemoglobin are lower around body tissues because oxygen dissociates from it to be taken up and used for aerobic respiration. There is also a certain amount of oxygen that is never taken up into the haemoglobin. This is known as dead space. On the graph to the left, you can see that curve makes a sigmoidal shape, with the graph being steeper at the beginning. This is because O2 saturation increases due to conformational changes in the haemoglobin protein. Oxygen saturation increases as partial pressure increases. It is most saturated in the lungs (close to 100%), so this ensures many oxyhaemoglobin molecules are formed. At lower partial pressures, it is more difficult for oxygen to bind. So as oxygen is unloaded unto tissues for respiration, the saturation decreases. Think of it being similar to phloem loading and unloading, with the lungs being the source and respiring tissues being the sink. What is the BOHR EFFECT? The Bohr effect shows that haemoglobin‟s affinity for oxygen is affected in certain conditions, meaning that it is less likely to bind with it. The curve „shifts‟ to the right if there is increased CO2 levels (from respiring tissues). This shows a decrease in oxygen affinity. This makes sense, as in this case, we‟d want oxygen to dissociate from haemoglobin to replenish these tissues. The curve „shifts‟ to the left if CO2 levels are low (as in the lungs), allowing more O2 to be taken up. pH is also a factor due to CO2 converting into carbonic acid and releasing H+ ions. Temperature affects haemoglobin as high temperatures can affect its structure and bonds, hence reducing affinity. 45 HISTOLOGY OF ARTERIAL TISSUE TS of carotid artery When drawing, remember to show: Cells or nuclei on innermost layer or endothelium Layer of elastic fibres beneath endothelium (thick wavy lines) Tunica media beneath elastic membrane Middle layer (tunica media) with dense fibres and smooth muscle Outer layer (tunica externa) with loose fibres and collagen tissue. 46 TOPIC 4: HOMEOSTASIS & HORMONAL ACTION 4.1: Discuss the concept of homeostasis. What is HOMEOSTASIS? Homeostasis is defined as the regulation of the body‟s internal environment in response to stimuli. This response is called feedback. Feedback can occur in two ways: Negative feedback, which attempts to reverse the change to a set point to achieve equilibrium (e.g. when blood glucose levels are too high, insulin is released to convert glucose to glycogen). Positive feedback, which reinforces the change that has happened and allows the process to continue (e.g. during childbirth, uterus contractions occur due to continued release of the hormone, oxytocin. Action potentials in nerves are propagated through continuous reactions.) There are many factors that are controlled in homeostatic processes, including body temperature, watersalt levels and blood pH. If these factors were to reach extremes, they would have severe effects on metabolic functions. For example, in high temperatures, enzymes can denature, and in low temperatures, not enough kinetic energy is available to initiate chemical reactions. Therefore, these factors usually have an optimal value, called a set point. For example, the set point for body temperature is 37.5 oC. Temperature is monitored by cells called receptors (or detectors) typically on the skin. These transport electrical signals to a regulator, which in this case, is the hypothalamus. The regulator compares this detected value to the set point, and sends out a signal if they are too far apart. If they are, a signal is sent to effectors, which try to bring the value back to the set point. In this case, if too high, sweat glands may be activated to cool the body down. If too low, skeletal muscles will contract continuously to produce heat (shivering). Changes in blood vessel diameters may also occur (vasodilation or vasoconstriction). The point of the negative feedback system is to achieve homeostatic equilibrium. It is important to keep in mind that hormones act a lot more slowly than electrical impulses from the nervous system. So, for factors such as blood glucose level, there is a delay between detection, regulation and action from the effector. As a result, there is a never a fixed return to set value. Instead, it hovers around a range as many factors are being regulated simultaneously. This is referred to as a dynamic mechanism. However, if a regulator or control centre is damaged, there won‟t be a return to a set point, possibly leading to disease of death. 47 4.2: Outline the general principles of hormonal action in animals. What is the ENDOCRINE SYSTEM? What occurs during a HORMONAL ACTION? Glands are tissues or organs that secrete a substance. There are two types: Type of gland Characteristics Examples Endocrine Secretes substances on the „inside‟. Ductless gland. Adrenal glands, pituitary gland, ovaries, testes. Exocrine Secretes substances on the „outside‟. Has ducts. Salivary glands, sweat glands, mammary glands, lacrimal (tear) glands. Hormones are defined as secretions of ductless glands that are directly released into the bloodstream. They can act on cells in the vicinity or on distant target cells that have receptors specific to the hormone. Hormones influence the metabolic activities of cells and act as chemical messengers. This system is known as the endocrine system and though it is slower-acting than the nervous system, some hormones bring about more long-term effects. Hormones tend to come in two main categories: Type of hormone Characteristics Examples Steroid Can diffuse through phospholipid bilayer. Lipid-soluble. Oestrogen, progesterone, testosterone, cortisol Nonsteroid Cannot diffuse through phospholipid bilayer. Lipidinsoluble. Typically made of polypeptides or amino acids. GH, ADH, adrenaline, oxytocin, insulin, glucagon FIRST AND SECOND MESSENGERS Non-steroid hormones that we‟ll encounter, such as adrenaline and glucagon, cannot diffuse through plasma membranes. Instead, they bind to receptor proteins on the plasma membranes. This usually stimulates the activation of an enzyme (sometimes by hydrolysing a protein and changing its shape) This enzyme converts ATP to a compound known as cyclic adenosine monophosphate (or just cAMP). cAMP is a second messenger, meaning that it will now „relay‟ instructions to the target cell from the first messenger, which was the hormone. In the case of glucagon, this means to convert glycogen to glucose. 48 EXAMPLES OF HORMONES & GLANDS IN THE BODY Observe the diagram below, which displays a layout of a few glands and their secreted hormones. Note that some of these hormones are for supplementary knowledge: Hormone ADH Adrenaline Calcitonin Cortisol Dopamine Erythropoeitin FSH Gastrin GH Glucagon GnRH Insulin LH Melatonin Oestrogen Oxytocin Progesterone Prolactin Thrombopoietin Thyroxine Basic description of function Assists with conservation of water, and water reabsorption in kidneys. Increases heart rate and breathing rate in periods of stress or excitement. Regulates levels of calcium and phosphate in blood, protects against bone loss. Increases blood glucose level, and assists in tissue repair in times of stress. A neurotransmitter that assists in cognitive function and reward. Plays a key role in erythrocyte production, especially in low-oxygen environments. Stimulates growth of eggs in ovary. Helps in regulation of menstrual cycle. Stimulation of acid and mucosal secretions in stomach walls. Acts on body tissues to stimulate growth. Promotes breakdown of glycogen into glucose. Stimulates the release of the hormones, FSH and LH. Promotes conversion of glucose into glycogen. Triggers the release of the egg from the ovary. Controls the body‟s sleep-wake cycle. Maturation of endometrium and egg cells. Promotes contraction of uterine contractions during labour. Used for human bonding. Maintenance of endometrium. Colostrum production and development of mammary glands. Promotes formation of thrombocytes (platelets) for blood clotting. Regulates metabolic activity such as digestion, energy levels and keratinous growth. 49 4.3: Explain how insulin and glucagon regulate blood glucose concentration What are the actions of INSULIN & GLUCAGON? Insulin and glucagon are two hormones secreted by the pancreas by a group of cells called the islets of Langerhans. These can be sub-divided into α-cells and β-cells. β-cells secrete insulin in response rise in blood glucose level. α cells secrete glucagon when blood glucose drops. Both cells act as receptors. Insulin is required to transport glucose from the bloodstream into cells‟ cytoplasm. Glucose is one of the raw materials for aerobic respiration and production of ATP. Glucose, however, is a large molecule and cannot diffuse through the phospholipid bilayer. It relies on transport proteins that will only „open‟ if insulin binds to one of its receptors. Muscle cells have a particular transport protein called GLUT4. However, these are held in the cytoplasm along vesicles. What insulin does is signal for these to come to the surface. As they fuse with the plasma membrane, glucose can enter via facilitated diffusion. In liver cells, it is a little different. No GLUT4 protein is necessary. Liver cells have insulin receptors on their plasma membranes, and two particular enzymes, glucokinase and glycogen synthase. Glucokinase phosphorylates glucose and moves it into the cell. Glycogen synthase, as you can guess, converts glucose into glycogen. Glucagon is mainly required to increase blood glucose levels. It can do this by breaking down stored glycogen (usually in the liver), or by converting other compounds such as lipids and amino acids into glucose (a process called gluconeogenesis). You may have heard of the latter occurring during starvation and muscle loss. The action of glucagon varies from insulin. The action of glucagon requires a first messenger and second messenger (outlined on previous page). The first messenger is the glucagon and the second is cAMP. Observe the diagram above. Step by step, this is happening: 1) Glucagon in the blood binds to a protein-coupled receptor on the liver cell‟s plasma membrane. 2) The protein is hydrolysed and „breaks off‟ a fragment, called a Gprotein, that acts as a molecular switch. This fragment completes a molecule of an enzyme called cyclase. 3) Cyclase converts ATP into cyclic AMP (cAMP). 4) cAMP then helps break glycosidic bonds in glycogen to form glucose. A note on G-proteins and cAMP G-proteins are complexes that act as signal transducers, broken off from larger proteins. Think of the process as the „parent protein‟ sending the „child protein‟ to relay instructions to an enzyme or another factor. cAMP‟s function can be likened to a piece of mRNA, but messaging instructions for reactions than for making proteins. 50 4.4: Discuss the commercial use made of ethylene in supplying market-ready fruit.. What happens during RIPENING? What is ETHYLENE? When a fruit ripens, it means that its internal components have fully developed. These include seeds, which are sometimes eaten by animals and dispersed via their faeces, where they grow into new plants. This process is advantageous to those species of plants as it reduces competition, introduces them to new habitats and encourages adaptation. When a fruit ripens, the following has occurred: Increase in edibility – The fruit attains characteristics for easy consumption, including the breakdown of cell walls to soften its texture, the increase in sweetness (due to complex sugars hydrolysing into simpler ones, such as sucrose) and the production of aromatic compounds, that instill scent and flavour. Change in colour – Fruits become brighter in colour (e.g. bananas turn yellow, cherries turn bright red) due to the conversion of the fruit‟s green chloroplasts to coloured chromoplasts. This makes the fruit more attractive to animals (including humans at the marketplace) and more likely to be consumed. Fruit ripening is caused by a plant hormone (or growth regulator) called ETHYLENE. Other growth regulators include auxins (for phototropic responses) and gibberellins (for seed germination). Ethylene is a GAS, meaning that it can undergo simple diffusion through the air and influence ripening on adjacent fruits. Ripe bananas can thus be placed in a container or in a warm room with other fruits to accelerate the ripening process and quicker produce market-ready fruits. This results in increased profits from grocers and farmers. Fruits that produce large amounts of ethylene are called climacteric fruits, including: tomatoes, bananas, avocadoes, mangoes, apples and pears. 51 How does ETHYLENE affects RESPIRATION? Many vendors prefer pick bananas while they‟re unripe as they‟re tougher (cellulose is still intact) and easier to transport in this state. Also, even one ripe banana in the bunch can prematurely ripen the others, giving the vendor little control over sales strategy. In addition to ethylene being a gaseous compound (and thus being able to diffuse quickly over a large area), it also activates enzymes within the fruit that act as catalysts to produce more ethylene. Therefore, once the process begins, ripening occurs at a rapid rate. This uses a considerably amount of energy, as a number of reactions are occurring in the fruit to hydrolyse cell walls and sugars to make them soft and sweet. Ethylene also has a low melting point, allowing it to remain a gas (and not condense) even at low temperatures. Rate of respiration increases as ethylene production is increased. This can be proven by observing carbon dioxide volumes released from the fruit. The graph below shows the relationship: The graph shows that as ethylene production increases (from Day 2 to 3), there is a steep increase in the evolution of carbon dioxide from fruit tissues due to increased rate of respiration. Both ethylene and CO2 concentrations reach a peak around Day 4. This is when the fruit has completely ripened. After this point, CO2 levels drop due to a reduction in metabolic activity after the ripening process has ceased. At the same time, ethylene concentration has „plateaued‟, meaning that it is still being released and can influence the ripening of other fruits around it. However, the quality of a fruit declines after this point, which will eventually result in cell death. Certain factors also influence this process, including humidity, temperature and oxygen concentration. 52 TOPIC 5: THE KIDNEY, EXCRETION & OSMOREGULATION 5.1 & 5.2: Explain the need to remove nitrogenous and other excretory products from the body; & describe the gross structure of the kidney and detailed structure of the nephron and blood vessels Why is EXCRETION necessary? What is UREA? If waste products from metabolic reactions are allowed to accumulate in tissues, they will become toxic. These waste products include carbon dioxide, excess water and urea. The removal of these products from the body is called excretion (also recall that egestion is the removal of non-metabolic waste, such as faeces). Urea is the main waste product formed during the process of deamination, which is the removal of the amino (NH2) group when an amino acid is broken down. The other parts of the amino acid (the carboxyl group, the R group and the hydrogen) go on to form ketone bodies, which are then used in gluconeogenesis. You may be familiar with this if you‟ve ever read about extremely low-carb „keto diets‟. As seen in the diagram above, the amino group is extracted to form the very toxic ammonia. In the liver cells, in a process called the ornithine cycle, ammonia, with the help of ATP, combines with carbon dioxide to eventually form urea. Urea has a lower toxicity and though less soluble, can be easily transported in the blood plasma. The GROSS STRUCTURE of the KIDNEY These are the main components of the kidney: - Renal artery – Carries blood from the aorta to the kidneys - Renal vein – Carries blood from the kidney back to the heart (vena cava) - Cortex – Outer part of the kidney, surrounded by a fatty tissue capsule. Contains the glomerulus and convoluted tubules of the nephron. - Medulla – Inner part of the kidney, containing collecting ducts and loops of Henle. - Ureter – Transports urine to the bladder. - Renal pelvis – Acts as a funnel for collecting urine flowing into the ureter. 53 What are NEPHRONS? Nephrons are kidney sub-units consisting of capsules, tubules and ducts. They are responsible for these processes: - Ultrafiltration – A build-up of capillary pressure forces small molecules in the capsules of the nephron into the tubules. These small molecules include water, glucose, sodium chloride and urea. Together, they form a filtrate. - Selective reabsorption – Certain nutrients (e.g. glucose) are removed from the filtrate and transported back into the bloodstream, leaving only the components of urine in the filtrate (e.g. urea and water) to be excreted. - Osmoregulation – With the help of the hormone, ADH, permeability of collecting ducts are affected dependent on body water levels and temperature. Water can be conserved in the blood this way. Though typically not depicted in the diagrams for simplicity, kidney nephrons are entwined with peritubular capillaries. These facilitate rapid transfer of materials away from the nephron filtrate (reabsorption) and into it (secretion). The diagram above shows the basic layout and functions segments of a renal nephron. It includes: Glomerulus – A cluster of blood vessels that filters blood to the Bowman‟s capsule. Bowman‟s (or glomerular) capsule – A cup-like sac that accepts the filtrate from glomerulus. Proximal convoluted tubule (PCT) – Site of selective reabsorption. Loop of Henle – Regulates the fluid and ion composition of the filtrate. Distal convoluted tubule (DCT) – Connects the loop to the collecting duct. Collecting duct – Responds to ADH by increasing wall permeability, allowing water to be reabsorbed. Transports urine to the renal pelvis and ureter. 54 5.3 & 5.4: Explain the function of the kidney in terms of excretion and osmoregulation; & discuss the clinical significance of the presence of glucose and protein in the urine. How does the kidney help with EXCRETION? Now that we‟ve seen the basic layout of a kidney nephron, we‟re now going to delve into the complex processes that occur in each segment. In the Glomerulus and Bowman‟s Capsule Firstly, you‟ll notice on the diagram two arterioles: the afferent and efferent. The afferent (or “arriving”) vessel brings blood into the glomerulus. The efferent (or “exiting”) vessel carries the blood away. Usually, the efferent arteriole would be much lower in concentrations of urea, glucose, water and amino acids, as these form the nephron filtrate due to ULTRAFILTRATION. Since the efferent arteriole lumen is smaller than the afferent‟s, this builds up hydrostatic pressure in the glomerulus. Smaller diameter increases ultrafiltration. In the Proximal Convoluted Tubule (PCT) As a result of this pressure, water and small solutes from the glomerulus are forced through pores in the capillary endothelium, and through the Bowman capsule‟s basement membrane, which acts as a „filter‟. The objective now is to transfer „useful‟ materials back into the bloodstream while at the same time, keeping waste molecules in the PCT, so that it can eventually form urine. PCT epithelial cells export certain ions and water back into the capillaries through active transport and diffusion. This happens through numerous villi and very thin membranes in the PCT epithelial cells, so they are lined with numerous mitochondria. The tricky part is the export of glucose. This involves the use of a sodium-potassium pump (more on this later). This allows two K+ ions to enter the cell, while at the same time allowing three Na+ ions to transfer out. As this occurs, glucose can be carried with these Na+ ions against the concentration gradient in a symport process. Think of it as Na+ opening a door for glucose to go along with it. More than half of the water exits the PCT during this selective reabsorption. Surprisingly, dissolved urea can also diffuse out of the PCT, as well. Any filtrate that hasn‟t been reabsorbed now flows to the Loop of Henle. In the Loop of Henle 55 We only need enough water to dissolve urea in the urine. After the PCT, the objective now is continued water reabsorption into the bloodstream. The Loop of Henle has a descending and ascending limb. In the ascending limb, sodium and chloride ions are actively transported into the cells and capillaries (called vasa recta) surrounding the descending limb. When these ions arrive at the capillaries and cells, they reduce their water potential. The “counter-current” type of flow in the Loop of Henle Due to the reduced water potential in the surrounding cells, osmosis now occurs, allowing water to flow from the descending limb to these cells and then into the capillaries, thus conserving water needed for metabolic reactions and cooling. At the base of the loop, the solute concentration is very high inside and out of the tube. This is also facilitated by the fact that the walls of descending limb is permeable. The ascending limb‟s walls are impermeable, so no water is lost here. In the Collecting Duct The collecting duct is located at the end of the nephron, just before urine is sent to the renal pelvis and ureter. The contents of the filtrate here are what constitute urine: primarily water, urea and any dissolved salts. Everything else should have been reabsorbed. Anti-diuretic hormone (or ADH) is a hormone secreted by the posterior pituitary gland. If the water potential of the blood is low (dehydration) or the environment is warm, ADH secretion is stimulated. If it is high or the environment is cool, ADH secretion is suppressed. The role of ADH is to aid in water reabsorption into the bloodstream and osmoregulation. ADH interacts with the plasma membranes of the collecting duct walls. If ADH is present in high amounts, water-transporting proteins called aquaporins move from the cytoplasm to line the duct‟s walls (similar to insulin‟s effect on GLUT4), increasing permeability to water and facilitating transport of water out of the duct. This water will possibly be used to form sweat. If ADH is in low amounts, no aquaporins will be present on the walls, so water is kept in the ducts and eventually excreted with the urine. This urine will be in larger volumes and quite diluted (or „clear‟ in colour). 56 Here‟s a recap of what we know about ADH: In low water potentials (or hot temperatures) In high water potentials (or low temperatures) ADH secretion stimulated. ADH secretion suppressed. Collecting duct walls increase permeability. Collecting duct walls remain impermeable to water. Aquaporins bind to surface membrane. No aquaporins on surface membrane. Water flows out of collecting duct. Water remains in collecting duct. Small volume of concentrated urine. Large volume of dilute urine. EXTRA NOTE: A person may produce unusually large amounts of diluted urine. This condition is called diabetes insipidus. Extremely small amounts of ADH is produced, leading to prolonged periods of dehydration and impermeability of the collecting duct walls. This could also result from a tumour in the hypothalamus or posterior pituitary gland. PRESENCE OF PROTEINS & GLUCOSE IN URINE Recall that urine is only supposed to comprise water, salts and urea. If any other solutes are present in a urine sample, then this is an indication of an issue or disease of the kidneys or cardiovascular system. These include: Component Present Reason Disease Implied Proteins Proteins are too large to pass through the basement membrane of the Bowman‟s capsule. With very high pressure or membrane damage, they can be present. Kidney failure, hypertension Glucose Capillary blood glucose concentration may be too high, limiting the diffusion of blood glucose from the PCT. Diabetes mellitus 57 HISTOLOGY OF KIDNEY TISSUE Though kidney tissue may be almost indiscernible in a light microscope due to high density and proximity of the nephrons, here are a few things to help with labels: Bowman‟s capsules are large and globular, looking almost brain-like. DCT‟s usually have less cytoplasm in their cells than PCT‟s and so appear to be more nuclear-dense. In better resolutions, a slight „brush border‟ (villi) may be observed in PCT‟s. Loops of Henle are typically tiny circles adjacent to each other. The thin segment of the Loop allows for diffusion of water and sodium ions and hence has to be thin to facilitate this. The thick segment of the Loop allows active transport so there are more transport proteins. It is also impermeable to water, so it has to be thicker. 58 TOPIC 6: NERVOUS COORDINATION This particular topic is quite complex and introduces many new concepts. For ease, let‟s familiarize or refamiliarize ourselves with some terms: Term Definition Neurone The fundamental cell of the nervous system. They are able to receive sensory input (sensory neurones), enact responses from muscles or glands (motor neurones) or connect the two (relay neurones). Nerve A tissue consisting of a group of neurones. Dorsal root ganglia A group of cell bodies that transmits sensory input to roots of spinal nerves. Dendron A branch-like extension of a neurone that propagates impulses received from other neurones. Smaller branches are called dendrites. Axon Long part of the neurone along which impulses are conducted. Myelin A protein wrapped around axons that acts as an insulator and also helps speed up transmission of impulses by saltatory conduction. Schwann cell Cells that „wrap‟ around axons to produce a myelin sheath. Node of Ranvier A gap in the myelin sheath, between adjacent Schwann cells. Stimulus A detectable change that produces a response in an organism. Sodium-potassium pump A protein located in many cells that creates an electrochemical gradient by „exporting‟ 3 sodium ions for every 2 potassium ions „imported‟. This means the inside of a cell is negative and outside is positive. Resting potential The state of a neuron relative to its surroundings when not stimulated or involved in passage of an impulse. Its electrical potential is usually -70mV. Action potential The change in electrical potential that results in the passage of an impulse along a neurone, e.g. to experience touch or move a muscle. Threshold potential The critical electrical potential where a stimulus occurs, but an action potential has failed to generate, e.g. a very gentle touch. Depolarization The shift in electrical charge of a neurone to initiate or propagate an electrical impulse. Refractory period A period when the electrical potential has a more negative value than resting potential, causing a delay in the subsequent action potential. Occurs during the phase of hyperpolarization. Synapse The junction between two neurones by which impulses may only pass with the aid of a chemical neurotransmitter. Acetylcholine (ACh) A neurotransmitter used at neuro-muscular junctions (motor neurones). Synapses that contain them are referred to as cholinergic. Acetylcholinesterase (AChE) An enzyme that rapidly breaks down acetylcholine to stop transmission of an impulse at a synapse. 59 6.1: Describe the structure of motor and sensory neurons What is the difference between SENSORY and MOTOR NEURONES? We‟ve established that the nervous system uses electrical impulses as very rapid messengers of sensory input from receptor cells, and carrying instructions to muscles or glands (effectors). This information is usually relayed to the spinal cord (via tissues adjacent to vertebrae called dorsal root ganglia) and the brain. The diagram to the left illustrates a MOTOR NEURONE. Starting from the top, you will see branch-like structures. The largest branch is called a dendron, which separate into dendrites. These allow connection to other neurones for reception and propagation of impulses. A cell body (or soma) is present at the end, containing organelles such as mitochondria to provide ATP to transmit impulses. These impulses travel along the long segments called axons until they get to axon terminals. At the end of these terminals are synapses, which are gaps that separate neurones but must still allow transmission of impulses. Notable about the axon is the myelin sheath. The myelin sheath allows rapid conduction of impulses and also acts as an insulator. Each „segment‟ of myelin is called a Schwann cell, and between each two Schwann cells is a small segment of axon called a Node of Ranvier. More on these later. The diagram to the right illustrates a SENSORY NEURONE. It is similar in structure to a motor neurone, but its cell body is located along the middle of the axon instead of at the end of it. These can be found on sense organs, such as the skin and retina to detect stimuli and pass them to the central nervous system (CNS) to be interpreted. If the stimulus is extreme (e.g. touching a hot stove), the impulse is passed to the dorsal root ganglia in the spine and directly to a motor neurone. This produces an involuntary action that moves the body away from danger. This action is called a reflex. Neurones are bundled into dense tubular tissues called nerves. A large stimulus may stimulate multiple nerves. 60 6.2 & 6.3: Explain the role of nerve cell membranes in establishing and maintaining the resting potential; describe the conduction of an action potential along the nerve cell membrane What is RESTING POTENTIAL? First, it is important to understand the concept of a membrane potential (or membrane voltage). This occurs when there is a difference in charge in the exterior and interior of a cell. For example, if the interior is negative and the exterior is positive. This produces an electrical gradient that allows charges to flow. If chemicals or ion concentrations are involved as well, it is called an electrochemical gradient. There are two main positive ions involved: Na+ and K+. The neurone is sometimes referred to as a ‘saltcovered banana’ (recall that bananas contain K), meaning that, when at rest (not firing impulses), it has more Na+ ions on the outside than there are K+ ions on the inside. This „uneven‟ distribution occurs due to proteins called sodium-potassium pumps. This pump, once interacted with ATP (active transport), can „push‟ Na+ ions out of the cell in return for „pulling‟ K+ ions into the cell cytoplasm. However, the trade is not equal. For every 3 Na+ pumped out, only 2 K+ are pumped in. Keep in mind that this is what happens in a neurone at rest. What this uneven trade does is ensure that there is a greater amount of positive charges outside than inside. The inside becomes negative. What also helps the above are channels on the membrane that are more permeable to K+ over Na+, and will quicker „leak‟ K+ ions out of the cytoplasm. This „difference in charge‟ generates a small voltage of approximately -70 mV (in humans). This is the resting potential of the neurone. It remains at that voltage, and at rest, until a stimulus (e.g. pain or heat) is detected. So to sum up resting potentials: Neurones are still „active‟ even at rest, trying to establish and maintain a „rest potential‟ of -70mV. The rest potential is attained by the „polarization‟ or difference in charge between the interior and exterior of the cell. The interior is negative and exterior is positive. The exterior is positive because there are much more Na+ ions there. A smaller number of K+ ions are inside. Hence, „salt-covered banana‟. There are also Cl- ions inside. This difference happens because sodium-potassium pumps allow 3 Na+ ions to leave for every 2 K+ that enter. Leaky channels permeable to K+ on the cell membrane also allow K+ ions to exit. So even more +ve charges on outside. This electrochemical gradient maintains the resting potential. 61 What is an ACTION POTENTIAL? An action potential is an event that coincides with the transmission of an electrical impulse. That is, when you actually experience a sensation or must contract or relax a muscle in response to a stimulus. Action potentials thus occur when the nerves are not at rest; they are experiencing action! We‟d just established that when impulses are not firing, the neurone is at rest. And a neurone at rest has a negative membrane potential of -70mV (due to the interior of the cell being negative). For an action potential to occur, we need the interior of the cell to be positive. But how? We need an influx of Na+ ions from those sodium-potassium pumps! Remember how there were „leaky‟ channels permeable to only K+? Some channels permeable to only Na+ are able to open with the right stimuli. For example, mechanically-gated channels in the skin open to allow Na+ to enter the cell in response to touch. So let‟s say that you get pinched. This pinch opens a Na+ channel in those local neurones that allow Na+ ions to diffuse rapidly into the cytoplasm from the outside, down the electrochemical gradient. The aim is to „even‟ out the +ve and –ve charges in and out of the cell to give a membrane potential of 0 mV, a process called DEPOLARIZATION. But this doesn‟t happen as expected. Instead, more Na+ rushes in than expected (sometimes called „overshooting‟), like an overbooked flight or a crowded store on Black Friday. Of course, the Na+ channels will be closed by now. Along the membrane are channels that open in response to this rise in voltage. These are known as voltage-gated channels and are permeable to K+ ions. These are like „guards‟ trying to disperse a crowd. As these channels open, K+ ions quickly shuffle out, trying to reduce the voltage of the cell back to the negative „rest potential‟. This is called REPOLARIZATION. You‟d expect the membrane potential to return to -70 mV, but instead it goes a bit more negative than that value (maybe -80 mV). This is called HYPERPOLARIZATION. The voltage-gated K+ channels are closed by now. This allows some time for those leak channels and sodium-potassium pumps to bring everything back to rest potential. The time it takes to return to rest is called the refractory period. And during this time, another action potential cannot take place. These „extra‟ Na+ ions inside the cell cause the interior to become positively charged, and the exterior to become negative (the opposite of „rest‟). The previously negative rest voltage of -70 mV is now a positive voltage of about 30 mV. 62 So to sum up an action potential: 1. 2. 3. 4. 5. 6. The axon membrane starts at its resting potential of -70 mV. All voltage-gated channels closed. The stimulus triggers voltage-gated Na+ channels to open. Na+ diffuse into the axon. More Na+ channels open, causing even more Na+ to diffuse in. (Depolarization) The membrane potential reaches about +30 mV, and voltage-gated Na+ channels close. Voltage-gated K+ channels now open, causing K+ to diffuse out of the axon. (Repolarization) K+ keeps diffusing out until the membrane potential is slightly more negative (about -80 mV) than resting potential (Hyperpolarization). K+ channels close. 7. Sodium-potassium pumps use ATP to return membrane potential to -70 mV (rest). During this time (refractory period), another action potential cannot take place. IMPULSE TRANSMISSION The electrical impulse is transmitted along the axon like an energy-carrying „wave‟ along the surface of the ocean. The „wave‟ itself consists of a series of depolarizations. One depolarized region impacts the successive region, and that becomes depolarized. This continues until the impulse reaches its destination. GRAPHING AN ACTION POTENTIAL The graph below shows all of the different phases of an action potential, along with some annotations of voltagegated channels and the movement of ions during each phase. Observe the graph and match it with the summary at the top of this page. Keep in mind that the axon cytoplasm at rest is negative (due to the excess of Na+ ions being pumped out of it). The depolarization phase „overshoots‟ (which is why it goes above 0 mV) and the repolarization phase „undershoots‟ (which is why it goes below resting potential). NOTE: Not all changes produce an action potential! If the stimulus is very small (for e.g. a sound below 20 Hz), it may not activate enough Na+ channels to cause depolarization. Thus, no action potential develops. It is said that the threshold for an action potential is between -50mV to -55 mV. Only around then will voltage-gated Na+ channels be activated. This is called the all-or-nothing law. 63 FREQUENCY OF ACTION POTENTIALS Unlike waves and forces, an action potential does not have a magnitude or amplitude. You can think of an action potential as a basic constituent of a sensation or impulse. If there are a small number of action potentials generated in a few neurones, it is most likely as a result of a weak stimulus, like a soft touch. If there are a large number of action potentials generated in many neurones, it is most likely a more strong stimulus, like a hard slap or a burn. Strong stimuli may also generate a high frequency of action potentials, which means that there are many occurring per second Anaesthetics such as Lidocaine, used by dentists, interfere with sodium channels to the point where, even with a strong stimulus, no depolarization occurs and thus no action potential is generated. SALTATORY CONDUCTION The word “saltatory” means “proceeding by leaps” as opposed to gradual or continuous movement. So saltatory conduction describes the way an electrical impulse skips across nodes of Ranvier down the full length of an axon. This continues until the impulse reaches its destination. Recall that a node of Ranvier is the gap between two myelin sheaths. Also recall that myelin is an insulator, which means that Na+ and K+ ions cannot be pumped through these. This means that action potentials cannot be generated in a myelinated segment of the axon! But they can be generated in a node of Ranvier. Thus: In a myelinated axon, the action potentials are conducted in a high velocity transmission as the spread of depolarization occurs in „leaps‟ across these nodes and not the myelin sheaths. In an unmyelinated axon, the velocity is much lower, as the action potential must be propagated from cell to cell along the axon in a continuous progression. 64 6.4 & 6.5: Explain synaptic transmission & outline the role of synapses What is a SYNAPSE? A fact that makes nervous transmission more complex is the involvement of synapses. Synapses are sites that lie between two adjacent neurones, which don‟t touch but have an extremely small gap that is 20 – 50 nm wide. That gap is called a synaptic cleft and the two neurones surrounding that cleft are called the presynaptic neurone (connected to an axon) and postsynaptic neurone (connected to a dendrite). Although action potentials can undergo saltatory conduction, they cannot „leap‟ across a synaptic cleft. Instead, the action potential is propagated from the preto the postsynaptic neurone with the help of a secreted chemical called a neurotransmitter, typically held in vesicles. One of the main neurotransmitters is called acetylcholine (or ACh), and synapses that secrete ACh are called cholinergic synapses. A synapse located between a motor neurone and muscle fibre is called a neuromuscular junction. A signal from such a synapse would cause muscle fibres to contract. Another neurotransmitter is GABA, which is in the brain cells. Depressants such as alcohol inhibit the production of GABA, producing the notable symptoms of slurred speech, delayed reaction time, reduction in motor skills, and dehydration due to suppressed ADH secretion. What are some FUNCTIONS OF SYNAPSES? Function Explanation Neural summation Summation is defined as the cumulative effect of several electrical impulses at a synapse. For example, when driving a car, many decisions must be made such as braking, turning, accelerating. Summation ensures that many different sectors of the brain are „firing‟ to decide which moves to make. Learning process The brain „records‟ data from receiving multiple signals from the various sense organs. Synapses allows these „memories‟ to coordinate and form new ideas. The more learning that occurs, the more these signals can „interact‟. Directed transmission Synapses direct impulses to travel to specific neurone pathways. This is important when doing precise actions. 65 How does an ACTION POTENTIAL „CROSS‟ A SYNAPSE? Action potentials must be able to propagate across a synapse in order to get from a presynaptic neurone to a postsynaptic neurone. Acetylcholine (ACh) is the neurotransmitter that acts as the „bridge‟ to get allow this action potential to „cross‟. Molecules of ACh are held in vesicles. On the presynaptic bulb, there are calcium and sodium channels. Let‟s outline what happens, correlated with the diagram on the right: 1. The action potential arrives from the axon. 2. Upon arrival of the action potential, channels open to allow Na+ and Ca2+ ions to enter the bulb‟s cytoplasm. The calcium ions stimulate movement of the vesicles towards the cleft and release their contents via exocytosis. Rapid diffusion of ACh occurs across the cleft. 3. On the postsynaptic membrane, there are receptors that are activated when an ACh molecule binds with it. These are called ligand-gated channels and when bound to ACh, they alter their shape to allow an influx of Na+ ions into the postsynaptic cytoplasm. This, of course, depolarizes the postsynaptic membrane and sets off another action potential, thus continuing the propagation as if it had „crossed a bridge‟. 4. An enzyme called Acetylcholinesterase (AChE) breaks down ACh into acetate and choline. This is done to „reset‟ the entire process and ensure that synapses don‟t keep „firing‟ constantly (this can possibly be seen with people who suffer from Parkinson‟s disease). 5. The choline is returned to the presynaptic bulb, where it re-forms ACh after using ATP to combine with acetyl CoA. A NOTE ON NICOTINE AND PESTICIDES Nicotine, like ACh, from cigarettes can bind to postsynaptic membrane receptors but, unlike ACh, cannot be broken down by AChE. As a result, the synapse keeps generating a high frequency of action potentials. This is why nicotine is considered a STIMULANT. Some insecticides and nerve gases contain malathion, which inhibit AChE by irreversibly deactivating it. Because ACh cannot break down, there is a rapid build-up and action potentials occur continuously, eventually leading to organ failure and death. 66 MODULE THREE – APPLICATIONS OF BIOLOGY THIS MODULE CONTAINS FOUR TOPICS: 1. HEALTH AND DISEASE 2. IMMUNOLOGY 3. SOCIAL AND PREVENTATIVE MEDICINE 4. SUBSTANCE ABUSE 67 TOPIC 1: HEALTH AND DISEASE 1.1 & 1.2: Discuss the meaning of the term „health‟; and explain the categories of disease and illness Before delving into this module, it is important to understand how the terms HEALTH and DISEASE are defined. The World Health Organization (WHO) defines each as: Health is a state of complete physical, mental and social well-being. Disease is the impairment of the functioning of the body and mind. There are numerous diseases that affect individuals in the world. Some of them are infectious (or communicable), which means that they can spread from one individual to another. Some of them are noncommunicable, such as lifestyle and hereditary diseases, meaning that they cannot be spread from one individual to another. Categories of disease (and examples) include: Category Description Examples Physical Occurs as a result of a physiological malfunction in the body, usually impairment of an organ or system. Diabetes, coronary heart disease, asthma, osteoarthritis Mental Occurs due to an impairment of the mind or deterioration of the tissues and matter within. Alzheimer‟s disease, clinical depression, schizophrenia Chronic A disease that is long-term, even lasting for a lifetime. Chronic bronchitis, diabetes Infectious Caused by the introduction of pathogens (viruses, bacteria, fungi, protozoans) to the body. Dengue fever, malaria, cholera, tuberculosis (TB) Social Caused by the individual living or working within an environment prone to contamination by pollutants (e.g. cigarette smoke) and pathogens, or not having access to a balanced diet. Tuberculosis, cholera, scurvy, rickets, night blindness Degenerative Caused by the gradual loss of function of tissues and organs. Alzheimer‟s disease, multiple sclerosis, osteoarthritis Hereditary Caused by inheriting alleles that translate to malfunctioning proteins. Sickle cell anaemia, haemophilia, cystic fibrosis (CF) Self-inflicted Also referred to as lifestyle diseases. These occur due to the intake of excess nutrition or drugs. Liver cirrhosis, lung cancer, coronary heart disease Deficiency Occurs due to the lack of a particular nutrient in the diet. Night blindness, scurvy, cholera, rickets, kwashiorkor. NOTE: It is important to realize that diseases are not restricted to a single category. For e.g. Cholera can be classed as physical, social and infectious. Diabetes (Type II) can be classed as physical, social, chronic and self-inflicted. 68 1.3: Analyse data involving incidence and mortality rates of disease. How does one ASSESS RISK OF A DISEASE? In order to study diseases and assess their immediate importance and risk, as well as observe them with respect to various epidemiological factors such as sex, age and geographical distribution, certain sets of data must be assessed and compared: Factor Definition Incidence The number of new cases of a disease in a given time period. Prevalence The number of people with a disease in the population at a current time. Mortality rate The number of people die from a particular disease (usually per year) ‟ Using the above graph as an example of data collection, we can observe that: The number of HIV cases (per 100,000) generally increased from 1982 to 2003, with small dips and fluctuations along the time period. One such dip would have been around 2001. After 2007, there was a sharp decline in cases, most likely due to increased awareness and antiviral technology. The number of AIDS cases was always less than HIV cases due to a dormancy period before AIDS develops, or that some cases may die before AIDS develops. AIDS deaths (mortality rate) are lower than AIDS cases, especially after 2001, possibly due to earlier detection and antibiotic treatment of opportunistic infections. 69 TOPIC 2: IMMUNOLOGY The topic of immunology is quite complex, so it is beneficial to familiarize and refamiliarize with some terms before reading about the topic. Term Definition Pathogen A disease-causing microorganism (bacteria, virus, fungi, protozoan). Vector An organism that transmits a pathogen from one organism to another (e.g. mosquito) Antigen A foreign substance which induces a specific immune response in the body. Antibodies An immunoglobulin. A blood glycoprotein that counteracts an antigen, destroying it. Phagocyte A white blood cell capable of absorbing and engulfing pathogens. These include monocytes, macrophages and neutrophils. Lymphocyte A white blood cell that originates in the bone marrow and either matures in the bone marrow (B-lymphocytes) or the thymus gland (T-lymphocytes). Humoral response An immune response mediated by antibodies produced by B-lymphocytes. Cell-mediated response An immune response not mediated by antibodies, but instead by phagocytes and Tlymphocytes. Memory cell A lymphocyte capable of responding to antigens long after its production. Histamine A compound released during inflammatory or allergic responses. Mast cell A cell that has granules containing histamines and heparin (a blood thinner). APC Antigen-presenting cell. An immune cell (usually a phagocyte) that processes and presents antigens to lymphocytes to initiate an immune response. Clonal proliferation Mitosis and multiplication of lymphocytes after recognition of an antigen, in order to counter it. Complements Proteins synthesized in the liver that enhance immune responses & phagocytosis. Passive immunity Short-term immunity that results from the introduction of antibodies from another source. Active immunity Long-term immunity that results from the production of antibodies from an immune response (sometimes acquired artificially from a vaccine) Monoclonal antibodies Antibodies produced from a cloned white blood cell fused with a cancer cell. Usually used for pregnancy tests, AIDS diagnosis, detect tumours, and cancer treatment. 70 2.1 - 2.4: Define the term, “immune response”; and distinguish between humoral and cell-mediated responses; the role of memory cells; the origin and maturation of B- and T- lymphocytes What are the various TYPES OF IMMUNE RESPONSES? The IMMUNE RESPONSE is defined as the reaction of white blood cells to the presence of a substance not recognized as a constituent of the body. Such a substance is referred to as a „foreign‟ substance or „non-self‟ substance. These non-self substances are usually contain structures called ANTIGENS, which the immune system can detect. Think of an antigen as something that triggers a burglar alarm. The two main types of white blood cells involved are PHAGOCYTES and LYMPHOCYTES. Phagocytes patrol the bloodstream (and can even leave) in search of non-self substances. When they encounter non-self substances, they engulf them. They may also engulf their antigens and „present‟ these antigens to other immune cells such as T-helpers (more on this later). They are usually short-lived. Lymphocytes originate in the bone marrow. B-cells mature in the bone marrow while T-cells mature in the thymus gland. - B-lymphocytes multiply and secrete antibodies, which counter non-self substances. T-lymphocytes can be „helper‟ cells, which stimulate Bcells and phagocytes. Or „killer‟ cells, which destroy the cells infected by the pathogen. Even though immune responses are complex interactions between these phagocytes and lymphocytes, they are categorized as HUMORAL (involving B-cells) or CELL-MEDIATED (involving T-cells). T killer cells are our primary defense against viruses. They usually secrete hydrogen peroxide into cells to destroy them with the viruses within. The chemical that the T helper cells secrete to stimulate other cells are called cytokines. 71 So let‟s compare the B- and T-lymphocytes once again: Factor B-lymphocytes T-lymphocytes Originate where? Bone marrow Bone marrow Mature where? Bone marrow Thymus gland Which response? Humoral (rapid response)) Cell-mediated (delayed response) Secretory products Antibodies Cytokines from T helper cells Differentiate into? Antibody-secreting plasma cells and memory cells T killer cells, T helper cells, memory cells (and more) Let‟s look at both immune responses a bit more in-depth: The B-cells experience a specific binding response, which means that the antigen must be in contact with the receptor on the B-cell surface membrane (similar to an enzyme‟s lock and key mechanism). T-cells utilize an APC (or antigen presenting cell), which will have the antigen attached to it (as in Bcells or dendritic white blood cells) , or engulfed within it (such as phagocytes). T-helpers and Tkillers will then bind to these antigens. Both B- and T-cells experience clonal proliferation, which means one clone is first selected and then divided multiple times to produce a large number of cells. Both B- and T-cells produce MEMORY CELLS, which provide long-term immunity and can provide rapid responses to antigens long after their production. As a result, the pathogens can be killed more efficiently during future infections. While B-cells produce antibodies to kill pathogens, T killer cells must destroy the entire infected cell, causing them to undergo lysis. Think of T killer cells as close quarter combatants, B-cells as snipers, T helper cells as messengers, and APC‟s as spies/recon. Memory cells are veterans who have already seen war. 72 2.5: Describe the mode of action for phagocytes. What do PHAGOCYTES do? Phagocytes are large white blood cells that have a MULTI-LOBED nucleus and operate by ingesting pathogens and non-self substances into their cytoplasm. They patrol the bloodstream and surrounding tissues (such as lung alveoli) using extensions of its plasma membrane called PSEUDOPODIA (Latin for „false foot‟). They ingest the pathogens via the process of ENDOCYTOSIS by extending and evaginating (wrapping) the pseudopodia around them. After the pathogen is ingested into a „sac‟ called a PHAGOSOME, organelles called LYSOSOMES secrete enzymes to digest the material. Digested products can then exit the cell via EXOCYTOSIS. However, sometimes the phagocyte will lyse and release chemicals called CYTOKINES to attract new white blood cells to fight the pathogens. NOTE: Recall that phagocytes can work as APC‟s to assist T-lymphocytes when they ingest the pathogen and its antigen. What is the INFLAMMATORY RESPONSE? Cytokines are able to interact with blood proteins known as COMPLEMENTS. These complements help activate enzymes in a complex series of enzyme reactions called the cascade process that lead to swelling, fever and redness (inflammation). Cells known as MAST CELLS release a chemical known as HISTAMINE, which makes CAPILLARIES dilate and more permeable to allow easy flow of blood (and white blood cells) to the inflamed location and even through the capillaries to infected tissues. This is why an inflamed area looks red. Dead, lysed white blood cells may remain in the area, forming PUS. Mast cells and histamines are unfortunately also responsible for allergies and autoimmune diseases (e.g. multiple sclerosis), where the immune system is misdirected to attack the body‟s own cells. 73 2.6: Relate the molecular structure of a typical antibody molecule to its function. How does an ANTIBODY work? Antibodies (or immunoglobulins) are blood glycoproteins secreted by B-LYMPHOCYTES during the HUMORAL RESPONSE of the immune system. They consist of light chains and heavy polypeptide chains connected to each other by DISULPHIDE bonds. Each antibody is specific to the antigen that attaches to it, similar to enzymes and substrates. There is one region that is common for all antibodies simply called the CONSTANT REGION. This does not change, no matter the type of antibody. What distinguishes each antibody is the VARIABLE REGION, which contains a specific antigen-binding receptor for its antigen counterpart. Think of variable regions as analogous to R groups in amino acids. Each antigen-binding receptor is also called a PARATOPE. These bind to regions on the antigen called EPITOPES. This may either neutralize the antigen or call phagocytes to action to destroy it. What are the PRIMARY AND SECONDARY IMMUNE RESPONSES? Inevitably, high antibody concentration results in a much more rapid immune response, but it does not come all at once. An initial exposure to an antigen, A, will yield a moderate conc. of short-term plasma cells until the infection is cured. This is called PRIMARY RESPONSE and occurs after a first vaccine dose or natural exposure. The primary response will also allow formation of long-term memory B-cells, so upon a second exposure to A, whether naturally or via a second (or booster) vaccine dose, these can be activated and differentiated into a greater conc. of plasma cells. This is the SECONDARY RESPONSE and allows much more rapid proliferation of antibodies, so antibody concentration steeply increases. Of course, since antibodies are specific to antigens, an exposure to a new antigen, B, will initiate a whole new primary response. 74 2.7 & 8: State what is meant by a monoclonal antibody; & describe their use in diagnosis and treatment. What is a MONOCLONAL ANTIBODY? How is it formed? The advent of monoclonal antibodies has been a hot topic in immunology, especially in the fight against the COVID-19 virus. A monoclonal antibody is an antibody made by cloning a unique B-lymphocyte. The purpose was to provide large amounts of one type of antibody for treatment and research. What‟s the difficulty? We must understand two things: 1. Cloned B- plasma cells do not secrete antibodies. 2. Antibody-secreting B- plasma cells do not divide. Scientists discovered, however, that fusing a B- plasma cell with a CANCER cell (which are known for their ability to divide and proliferate) can form a B- plasma cell that CAN divide! This fused cell is called a HYBRIDOMA. These hybridoma can then naturally proliferate in fermenters and produce an enormous amount of monoclonal antibodies. Scientists had used mice to stimulate production of the initial B- plasma cells by injecting them with the counterpart antigen. Monoclonal antibodies are used in a cancer treatment drug called MabThera to treat non-Hodgkin lymphoma and kill mutated cancer cells. They are also used in pregnancy tests, AIDS diagnosis, tissue typing, and tumour detection. How do MabThera work? MabThera is the brand name for a target cancer drug called Rituximab. It is a treatment for a few types of lymphomas and leukaemias. It is a monoclonal antibody that targets a protein called CD20 on the surface of malignant B-cells, which contribute to the cancerous diseases. The killer T cells of the immune system then pick out the marked cells and destroy them. It is important to destroy as many of these malignant Bcells quickly, as they quickly replenish. This quick targeted production makes monoclonal antibodies an efficient method of cancer treatment. 75 How do PREGNANCY TESTS work? Most pregnancy tests use a dip stick that comes into contact with the pregnant woman‟s urine. If you recall, a woman produces a hormone known as hCG to maintain progesterone production during gestation. I – Here is the reaction zone coated with mobile mouse monoclonal antibodies that can specifically bind to hCG. These have an enzyme that activates a coloured DYE (usually blue) attached to them, so if hCG is present, the antibodies can carry the dye. If not, no dye is activated and the urine and antibodies „wash‟ through. II – This is the result window. This contains fixed hCG antibodies. If hCG is present, the antibodies will bind to the dye in I and produce a blue line to indicate a positive result for pregnancy. If no hCG, no dye activates and this window is blank. III - A control window is present that reacts with the urine to ensure the dip stick is functional. This happens with a positive or negative result. This window contains anti-mouse antibodies and dye, so these will activate when binding to the mouse antibodies in I. NOTE: Keep in mind that the control region with the anti-mouse antibodies are NOT specific to hCG, unlike the regions in I and II. Also keep in mind that monoclonal antibodies are made in mice. How can each reaction be described? Reaction A is in the control window, due to the presence of anti-mouse antibodies and activated dye. Note that no hCG is bound to the enzyme-dye antibody. This will produce a blue line, positive or not. Reaction B is in the reaction zone, where urine is picked up. hCG was found in the urine, which is why it is bound to the monoclonal antibodies here. The dye is yet to be activated. Reaction C is in the result window, showing the enzyme-activated dye and antibodies bound to hCG. This will produce a blue line due to a positive result. 76 2.9 & 2.10: Distinguish between active and passive immunity, natural and artificial immunity; and explain the role of vaccination in providing immunity. What are the VARIOUS TYPES OF IMMUNITY? We‟ve already understood how primary and secondary responses to infection take place, seeing that immune responses happen due to exposure of non-self substances or antigens that are attached to pathogens or toxins. This immunity occurs due to the production of antibodies from B-cells. This can be passive (if antibodies are introduced from an external source, e.g. monoclonal antibodies) or active, if the body is allowed to produce its own antibodies and memory cells (such as with a multi-dose vaccine). Using COVID-19 as an example, let‟s break down four types of immunity: Type Definition / Note Naturally acquired active If one contracts COVID-19 due to contact, they undergo a primary response and their B-cells develop antibodies and memory cells. Therefore, naturally acquired active immunity is obtained from the primary response to pathogen exposure. Natural passive Occurs when a foetus prenatally obtains antibodies through its mother‟s placenta while still in the uterus. Postnatally, the baby obtains it from breast milk. Therefore, natural passive immunity is obtained from mother to offspring transfer of antibodies. Artificially acquired active Also called vaccination. severely reduces the chance of contracting COVID-19. A weakened form of the pathogen, an antigen or instructions to build the antigen (mRNA) is introduced to the bloodstream to stimulate a primary response and longterm immunity. Therefore, artificially acquired active immunity is obtained from the primary response due to intentional exposure to the antigen/pathogen. Artificial passive If one has contracted COVID-19, vaccination is not an option as that is a preventative measure. A common treatment is the use of external monoclonal antibodies introduced to the patient as a serum. These can quickly reduce pathogen number but does not provide long-term immunity as no memory cells are developed. Therefore, artificial passive immunity is the short-term immunization obtained from the injection of antibodies. 77 What are the ARGUMENTS FOR AND AGAINST VACCINATION? We‟ve just learnt that vaccines are considered ARTIFICIALLY ACQUIRED ACTIVE IMMUNITY, which means that it stimulates the production of antibodies due to intentional introduction of a pathogen (or its components). Vaccines are used for COMMUNICABLE (infectious) diseases such as measles, HPV, rubella and malaria. They have numerous modes of action, including: Live attenuated vaccines – containing weakened forms of pathogens. Inactivated vaccines – containing pathogens that cannot reproduce but can still be detected. Subunit vaccines – containing a detectable component (e.g. viral spike protein) of the pathogen. mRNA vaccines – containing the mRNA blueprint of a pathogen or its component, so it can be synthesized or „rebuilt‟ in the body for detection. Vaccines have been successful at near-eradicating diseases such as polio and smallpox. However, measles, a contagious disease once thought near-eradication had seen a resurgence in the U.S. in 2019 due to a decrease in vaccination rates. Vaccination rates must be around 80% to achieve what is called herd immunity, to reduce the reproductive rate and spread of the pathogen. When people have doubts about taking the vaccine, this is called vaccine hesitancy. Below are a few reasons and responses for vaccine hesitancy: Reason Response Viruses mutate often. Viruses replicate rapidly, which increases chances of mutation, leading to variants. The antibodies produced by vaccines thus cannot detect mutant antigens fast enough. However, some vaccines (especially subunit and mRNA) tend to focus on antigens that have the lowest risk of mutation. Vaccines cause allergic reactions. Severe allergic reactions (or anaphylaxis) to vaccines are rare. Physicians should always be consulted before getting a vaccine. Antihistamines can be used to mitigate allergic reactions in some cases. Fortunately, there may be more than one brand or make of vaccine for critical diseases, some not containing allergic components. The immunocompromised are at risk of getting ill with the vaccine. Very young children or older people with severe co-morbidities often have concerns about taking vaccines due to concerns about not being able to withstand the primary immune response. This is a legitimate concern and once again, physicians should advise those individuals of risk on a case by case basis. Spread of misinformation This is a sensitive topic. Most vaccines comply by religious rules (such as being halal). There had once been a popular claim that vaccines cause autism, which turned out to be a hoax. Education and awareness campaigns should be prominent enough to penetrate vaccine-hesitant populations without making the decision to get vaccinated unsavoury. As said, this is a sensitive and complex topic. 78 TOPIC 3: SOCIAL AND PREVENTATIVE MEDICINE 3.1: Discuss the causative relationship among diet, obesity and diabetes. What is OBESITY? We‟ve learnt that consumption of foods that contain carbohydrates and energy-dense lipids are used to form ATP. However, when consumed in excess, a large portion of those molecules get converted for storage and become deposited in ADIPOSE cells, found below the dermis and around tissues, such as in the liver and coronary arteries. This highly increases the chances of developing Type II diabetes, CVD‟s (cardiovascular diseases), kidney failure and fatty liver disease. . A measurement called BMI (Body Mass Index) is sometimes used to define obesity. The calculation is done by using the formula to the left. If the result from this calculation is 30 or over, an individual is considered obese. Note that this measurement does not take into account factors such as muscle mass and can falsely claim obesity in people like bodybuilders. Recall that a BALANCED DIET is defined as one that contains all the different nutrients required by the body in the appropriate proportions to supply energy. Any nutrient deficiency may lead to a disease such as scurvy (lack of Vitamin C) or night blindness (lack of Vitamin A). What is the link between DIET, OBESITY and DIABETES TYPE I AND TYPE II? Recall that the pancreas is a major organ within the endocrine system. It secretes two hormones that regulate blood glucose level, INSULIN and GLUCAGON. Insulin binds to insulin receptors on cell plasma membranes. These allow glucose molecules to enter the cytoplasm of the cell to begin glycolysis and enter the mitochondria to produce ATP. It also helps convert glucose to its storage form, GLYCOGEN, by this means. Diabetes, whether be Type I or II, restricts this movement of glucose from the blood capillaries into the cell cytoplasm, resulting in fatigue and dehydration and, in worse cases, tissue necrosis and amputation. Type I diabetes – the pancreas of the people who suffer from this type usually produce little to no insulin. This form of diabetes is genetic and usually diagnosed in childhood or in early adulthood and the people who have the condition usually need to use insulin all their life. Type II diabetes – in this type of diabetes, the patient‟s pancreas produces insulin, but the insulin receptors on cells do not respond, usually due to impairment caused by fatty accumulation and sedentary lifestyles. This is called INSULIN RESISTANCE. The people suffering from this type of diabetes usually receive oral medication (e.g. metformin) to help with the processing of the insulin. Long-term regular exercise can be done to stimulate the cells‟ insulin receptors, negating insulin resistance effects. 79 Naturally, when a person consumes a sugar, that sugar is digested and absorbed into the bloodstream from the small intestine, thus causing an increase in blood glucose level. Blood glucose level decreases when the glucose enters the cytoplasm of the body cells to be used for ATP. Recall that this is called ASSIMILATION. In diabetics, assimilation is delayed. It is therefore recommended that the consumption of carbohydrates (especially refined) is limited to avoid a continuous buildup of glucose in the bloodstream. After an 8-hour „fast‟, diabetics usually have a higher blood glucose level than non-diabetics. Typically, the normal fasting range is given as 70 – 130 mg/dl blood glucose. Above that range, the individual is considered prediabetic or diabetic. 3.2: Describe the effects of fats on the cardiovascular system. What causes ATHEROSCLEROSIS and CORONARY HEART DISEASE (CHD)? Recall that arteries are high-pressure blood vessels with thick muscular walls and small lumens. They transport blood away from the heart and towards body cells. This blood contains oxygen used for aerobic respiration. ATHEROSCLEROSIS can lead to these arteries becoming blocked due to accumulated deposits of LDL‟s (low-density lipoproteins that are high in fat content, commonly known as „bad cholesterol‟) and chemicals from TOBACCO smoke. These form a PLAQUE that adheres to the arterial walls, reducing the lumen size and limiting blood flow. This also increases blood pressure. High pressure blood flow can make the plaque break, causing blood to enter and form a clot called a CORONARY THROMBOSIS. This further reduces lumen size and reducing blood flow to body cells. Worse yet, this blood clot can fracture and enter a coronary artery that supplies blood to the heart muscles, thus cutting off their oxygen supply. This is called a MYOCARDIAL INFARCTION and is what leads to a heart attack. NOTE: You would‟ve noticed that people frequently get heart attacks during great periods of physical or mental exertion (exercise or stress). This is because these generate high-pressure blood flow, which will lead to rupturing of the coronary thrombosis, most likely leading to the clot „clogging‟ the coronary arteries. 80 What are HYPERTENSION and STROKE? Hypertension and stroke are generally associated with atherosclerosis. Recall that atherosclerosis causes arterial lumen size to decreases. This decrease in size means that less area is available for blood to flow to body cells unless the heart can apply more force or beats per minute. A decrease in area and an increase in force equates elevated blood pressure levels or HYPERTENSION This is usually considered to be above 140/90 mm Hg (the numbers respectively representing systolic and diastolic pressure). A STROKE is caused by acute damage to the brain. Almost similar to a myocardial infarction, a ruptured coronary thrombosis can become lodged in a blood vessel connected to the brain, thus depriving it of oxygen and glucose. The person can die if this carries on for long enough. If they survive, it is likely their memory and motor skills are affected, including paralysis. 3.3: Discuss the consequences of exercise on the body & the benefits of maintaining a physically fit body. Exercise can be defined as activity requiring physical effort, carried out to sustain health and fitness. Exercise has numerous long-term and short-term physical benefits, but also mental as it is known to release chemicals called endorphins from the brain, which improve mood and well-being. A major long-term effect to observe is the increase in VO2 max. This is the maximum rate of oxygen use during aerobic respiration before switching over to anaerobic respiration. In other words, muscles and other body cells can use oxygen quickly to allow pyruvate to turn into ATP. A high VO2 max means that the individual can exercise at a faster rate without switching to anaerobic respiration to produce lactate. Long-term consequences of exercise: Aspect Long-term effect Cardiac efficiency Increase in red blood cell count and oxygen-carrying capacity. Increase in heart muscle size and stroke volume (vol. of blood per heartbeat) Increase in VO2 max to increase efficiency of oxygen usage by muscles. Muscles Increase in number and size of mitochondria Increase in cross-sectional area of muscles, as well as glycogen storage. Increase in number of capillaries in the muscle, improving oxygen supply Increase in myoglobin pigment, leading to increased O2 storage in muscle Reducing risk of NCD‟s Maintaining a healthy body mass reduces risk of chronic NCD‟s such as Type II diabetes, coronary heart disease, hypertension, stroke and kidney failure. 81 There are also numerous short-term effects of exercise, which are usually physiological changes and adaptations that occur to supply muscles with more oxygenated blood and increase removal of CO2. Short-term consequences of exercise: Aspect Short-term effect Gaseous exchange Increase in breathing rate and tidal volume (amt of air circulating in lungs) Increases diaphragm and intercostal muscle contractions; caused by increase in acidity detected by chemoreceptors Circulation Increase in heart rate due to adrenaline secretion and nerve impulse activity in pacemaker. Secretion of nitric oxide from blood vessels due to low oxygen levels, which dilates arterioles and increases blood flow to the heart (cardiac output) and to the muscles. Dilation of arterioles lead to heat loss through the skin (leading to „flushed‟ appearance). 3.4 & 3.5: Describe the mechanisms of infection & modes of transmission for viral diseases and their causative agents A short recap on PATHOGENS and VECTORS We previously learnt that pathogens are disease-causing microorganisms that can be transmitted from one organism to organism through vectors. For example, the protozoan pathogen Plasmodium falciparum, which causes malaria, can be picked up by Anopheles mosquitoes from infected humans spread the disease to uninfected humans. Here are a few examples of types of pathogens and their infectious diseases: Pathogen Type Example diseases Bacterium Cholera , Tuberculosis, Typhoid, Tetanus, Leptospirosis, Syphilis Virus Dengue fever, AIDS, Herpes, Cervical Cancer, Influenza Fungus Ringworm, Candidiasis (yeast infections), Athlete‟s foot (T. crucris infection) Protozoa / Protoctist Malaria, Chagas disease, African Sleeping Sickness In this objective, the focus will be on two viral diseases: dengue fever and AIDS. It is notable that viruses cannot be killed by antibiotics, like bacteria. Instead, antiviral drugs, artificial passive immunity (e.g. monoclonal antibodies) and immune responses are relied upon to fight viruses. 82 What is DENGUE FEVER? Dengue fever is a viral mosquito-borne disease that usually occurs in tropical areas of the world. Its signs and symptoms include a high fever, muscle and joint pain, severe headache, nausea and skin rashes. In more severe versions of dengue, called dengue haemorrhagic fever, blood vessel linings become damaged and the blood clotting process is interrupted. As a result, internal bleeding occurs. The vector for the dengue virus is the female Aedes aegypti mosquito, which injects its proboscis (mouthparts) into the skin and draws blood from a vessel. Its saliva enables this to happen without clotting. If the bitten person has the dengue virus in their skin cells, the mosquito will draw it in as well and become a vector. If the mosquito then bites an uninfected person, the virus will enter their skin cells. After an incubation period of 4 - 10 days, signs and symptoms start to appear. How do VIRUSES ENTER CELLS AND SPREAD in the body? Observe the diagram to the right: 1. Attachment – Viral spike proteins bind with receptors on cell surface membrane to allow entry. 2. Entry – Virus enters cell via endocytosis, where it is taken into by a vesicle. The capsid breaks down, releasing RNA. 3. Replication and Gene Expression – The RNA uses the enzyme, reverse transcriptase, to make multiple DNA copies of itself. 4. Assembly - Synthesis of new viral proteins is done in the rough ER and ribosomes (translation) 5. Release – New viruses are packaged into vesicles by the Golgi body and fuse with the cell‟s plasma membrane to produce its phospholipid coat. The virus then exits via exocytosis. NOTE: Think of the virus transforming a cell into a „photocopying‟ or „cloning‟ machine to make copies of itself, with the RNA being the „rogue instructions‟ being fed into it. HIV is worse because that host cell is usually a T helper cell called a CD4 cell. The cells are eventually destroyed, compromising the immune system to pathogens and opportunistic infections. More on this later. 83 What is AIDS? AIDS is the most advanced stage of HIV infection. It is a disease of the immune system, where the HIV (Human Immunodeficiency Virus) invades helper T lymphocytes called CD4 cells. Recall that helper T cells help signal to phagocytes and other lymphocytes to rally together to attack an infection. Not having these leaves a lot of these other white blood cells „in the dark‟. The T-cells‟ nucleic genetic code is rewritten to produce even more HIV copies, just as seen on the previous page. When the helper T cell count falls below 200 cells per mm3 of blood, the patient is now said to have AIDS (Acquired Immune Deficiency Syndrome). The AIDS patient‟s immune system now is highly compromised and produces serious complications if the patient contracts another viral infection, known as an opportunistic infection, such as influenza. Symptoms of HIV/AIDS include: persistent fever, severe weight loss (wasting), recurrent pneumonia, lesions, persistent diarrhoea. HIV can be transmitted from person to person by means of bodily fluid exchange, such as: Unprotected sexual intercourse – due to exposure to semen, vaginal fluids and blood (if vaginal or anal linings are damaged) Through the placenta – from mother to foetus if antiretroviral therapy isn‟t employed. Can also occur during childbirth. Breast milk – from HIV-infected mothers, though the level of risk is unknown Blood transfusions – due to transfer of contaminated blood during surgeries or while sharing hypodermic needles. HIV can be detected by doing blood tests. However, it has an incubation period of about 3 months, which means that a person could have contracted HIV two months ago and still test HIV-negative. There is currently no vaccine for HIV/AIDS. However, antiviral drugs such as AZT (azidothymidine) can be used to preserve T-cell count and prolong life. These drugs are expensive, unfortunately, and not affordable to the common citizen. 84 3.6: Discuss reasons for the regional distribution of AIDS, diabetes and cancer. What affects regional distribution of AIDS and DIABETES? With respect to total HIV/AIDS population in the Caribbean, the top three countries are Haiti (1.9%), Jamaica (1.7%), and Trinidad and Tobago (1.5%). In sub-Saharan Africa, prevalence is 5.0% while in East Asia, it is only 0.1%. The factors that affect this distribution include the following: Factor Notes Culture or lifestyle Due to stigma and unwillingness to admit HIV status or get tested, many people with multiple partners unknowingly transmit the virus. Some cultures encourage more liberal views on sexual freedom, while others discourage use of contraception (condoms). All of this encourages spread. Long incubation period Since HIV may not be detected by blood tests until 3 months into incubation, an HIV-positive person can unknowingly spread it. Ease of travel Wherever there is a large number of tourists, especially those partaking in „sex tourism‟ with locals, the virus can quickly spread to local populations. Availability of drugs and condoms Drugs that help mitigate the effects of HIV (e.g. AZT) are expensive and hard to obtain. In some countries, condoms are not commonly available Poverty Poverty and high unemployment rates may encourage sex work, which facilitates spread if done irresponsibly. Some countries may not be able to avoid antiretroviral therapy for patients and pregnant mothers. Lack of education Citizens of some countries simply do not understand how the virus is transmitted or may have false beliefs in „curing‟ it (e.g. intercourse with virgins). Some may even believe that heterosexuals cannot contract HIV. And these are factors which influence prevalence of Type II diabetes: Factor Notes Diet In some countries, „fast food‟ is the most economic and convenient option. Some cultures also prioritize foods that are high in refined carbohydrates and LDL‟s (e.g. „doubles‟ in Trinidad). Overconsumption of these foods leads to obesity, which greatly increases risk of diabetes. Sedentary lifestyle Countries or areas with long hours of office work and no time for outdoor recreation raises risk of obesity and diabetes. Prenatal malnutrition An ongoing study has linked malnourished mothers to children who are more likely to develop Type II diabetes later on in life. Ethnicity and genetics People of African and Asian descent are observed to more commonly develop Type II diabetes. 85 What affects regional distribution of CANCER? Cancer is a general term given to a group of diseases where cells in a certain organ or tissue uncontrollably divide. These form lumps called tumours, which can then break away and form tumours in other parts of the body, a process called metastasis. Bear in mind that tumours can be benign, which means that they are harmless. Age influences cancer risk, as the cancer cell is usually formed due to a random mutation. Certain repressor genes help prevent these mutations, but those can also mutate and lose function if enough time passes. There are several substances capable of causing cancer, called carcinogens. Some of these are found in: - Cigarette smoke chemicals (e.g. nitric oxide) Ionizing radiation (e.g. X-rays) Food additives and certain artificial sweeteners (e.g. saccharin) Viral RNA (e.g. human papilloma virus, or HPV, which causes cervical cancer) Going with this, we can also deduce what affects regional distribution of cancer cases: Factor Notes Environmental hazards Chemicals from factories or buildings such as asbestos and vinyl chloride can affect employees or tenants over time. Also, places that allow exposure to secondhand smoking. Outdoor environments subjected to frequent UV radiation (from the Sun) without high SPF sunscreen can increase risk of melanoma (skin cancer). Indoor ones subjected to ionizing radiation (e.g. nuclear power plants, labs or clinics) should also take the proper precautions to avoid exposure. Food additives Regions that use food additives that contain benzoates may be at risk of cancers. Viruses HPV, which causes cervical cancer, can be transmitted via sexual intercourse. In areas where people usually have multiple partners and condom use is rare, this type of cancer can quickly spread to women. Genetic factors Alleles that express risk of developing certain cancers can be higher in concentration in certain countries. For example, the Caribbean has a relatively high amount of alleles that result in mutations leading to breast cancer. Failure to seek treatment on time Since mortality rates are affected by how quickly cancer is detected and treated, it is important for a patient to observe their symptoms and visit a physician for screening (e.g. mammograms for breast cancer) or biopsies (tissue samples). Unfortunately, in many developing nations, this is very difficult for the common citizen and they may not seek treatment until it has metastasized. 86 3.7: Assess the impact of communicable and non-communicable diseases regionally. What are some IMPACTS OF DISEASES ON SOCIETY? Factors are listed and explained below: Factor Explanation Economy If a disease becomes uncommonly prevalent, it puts a strain on State-funded medical care. Charities and volunteers may have to step in to reduce the financial impact. Money has to also be diverted to awareness campaigns for the disease, as well as the purchase of PPE (personal protective equipment). Patients won‟t be able to work while ill, so there will be reduced labour force and overall drop in productivity. In cases where nationwide quarantines and lockdowns are necessary for communicable diseases, this can result in businesses closing down. Trade relations Due to decrease in productivity, there will be reduced income from exports of locally manufactured goods. Tourism sectors may suffer due to stigma of contagious diseases. Food availability If the agricultural sector is affected by reduction in labour force, there will be food shortages and increase in food prices as a result. Household income There will be high costs for privatized healthcare and medical bills, in addition to reduced income from unemployment if a breadwinner has fallen ill or become debilitated by their disease (e.g. a stroke) Quality of life The emotional toll of illness and death reduces the quality of life for either individuals or families. In the case of lockdowns, being quarantined for lengthy periods has a psychological toll. Positive change and awareness When a disease, especially one that is self-inflicted, becomes prevalent in a society, many individuals make a positive change in their lifestyles to avoid developing that disease. This includes changing their diets to include less LDL‟s and carbohydrates, quitting smoking, exercising more often or, in the case of infectious diseases, washing their hands more often. 87 3.8: Discuss roles of social, economic & biological factors in the prevention & control of viral infections. What are the roles of factors involved in PREVENTION & CONTROL OF VIRAL INFECTIONS? Factor Explanation Quarantine and selfquarantine Previously explained. Quarantines can limit the spread of a viral infection, especially if caused by droplet infection, but can also have a severe effect on businesses and household earnings. (social & economic) Those aware of their symptoms should practice staying away from the workplace and others. Resting at home is the best option when no vaccine or drug can be prescribed, such as with dengue fever. PPE (biological) Safe sex (social) Sanitation (economic) Pest control (economic) The use of PPE, such as masks, help limit the spread of viruses via droplet infection. Note that they do not prevent the wearer from contracting it, as viruses are very small and can sometimes pass through the material of the mask. By being faithful to one‟s partner, limiting partners or ensuring condoms are worn during sexual intercourse, viral STI‟s can be prevented, such as HIV and herpes. Workplaces and public buildings should be sanitized with disinfectants on a regular basis. Keeping refuse from piling up also reduces chance of vector breeding. Some viruses are spread via insect and animal vectors, such as dengue virus and yellow fever virus. By clearing out stagnant water sources, mosquitoes have no breeding grounds for their eggs. Insecticides could be sprayed in areas where mosquito-borne viruses are common. Vaccination (biological) Regular screening (biological) Awareness campaigns (economic) Antiviral drugs (biological) Individuals who are vaccinated against a virus are much less likely to contract that virus as they have already developed antibodies to produce a rapid immune response against it. This limits spread of that viral infection in populations. The spread of viruses, such as HIV, can be limited if sexually active people get their blood screened after each new sexual partner. Campaigns to disseminate information to the public is always helpful in educating about limiting spread and infection. Antiviral drugs and monoclonal antibodies can be used to treat some viral infections, if available. 88 TOPIC 4: SUBSTANCE ABUSE 4.1 & 4.2: Discuss the meaning of term “drug abuse”; psychological and physical dependence What is a DRUG, and DRUG ABUSE? A drug is defined as an externally administered substance that alters the body‟s physiology. Its internally produced counterpart may be something akin to a hormone. They are used for a number of purposes, such as treating illness or therapeutic purposes (e.g. penicillin, quinine, tetracycline, diazepam), as painkillers (e.g. morphine, ibuprofen, naproxen) or for recreation (e.g. nicotine, alcohol, cannabis). Drugs can be legal or illegal and may fall into four main categories: Stimulants, which increase nervous activity (e.g. nicotine, cocaine, caffeine) Depressants, which reduce function and nervous activity (e.g. alcohol, codeine) Hallucinogens, which cause perceptual anomalies (e.g. cannabis, LSD, PCP) Analgesics or Opioids, which act as pain relievers (e.g. heroin, morphine, fentanyl) Drug abuse occurs when the use of the drug leads to physiological or psychological harm to the user, their family or society at large. This can happen with illegal drugs, such as cocaine, which would lead to drug dependency, withdrawal symptoms and possibly, overdose. The progressive decrease in response to a drug is called tolerance. This can also happen with legal drugs such as antibiotics, antidepressants, such as the brands Prozac and Xanax, where the drug may be used for therapeutic reasons but have addictive mood-changing properties. A good example of this is the depressant, codeine, which is an ingredient in the mood-altering drink, Lean. What are the types of DRUG DEPENDENCY? Observe the cases below: 1) Sandra is 40 years old and uses heroin in two to four injections, four to twelve hours apart. When she goes for longer than twelve hours without heroin, she feels sick and becomes anxious. 2) Wayne is 16 years old and smokes cannabis with his friends. He often goes without cannabis for days at a time, with no ill effects. However, after a week has passed, he feels a strong urge to smoke, especially when he feels depressed or bored. Sandra shows PHYSICAL dependence on the drug due to strong cravings and withdrawal symptoms, such as nausea and restlessness if the drug is abrupt reduced or stopped for short periods. Symptoms worsen as frequency of drug abuse increases and tolerance of the drug builds up. Wayne shows PSYCHOLOGICAL dependence on the drug due to lack of strong withdrawal symptoms and cravings, ability to go prolonged periods without the drug. Use of the drug usually due to influence of societal factors and occurs when mentally unstimulated by other aspects of life. 89 4.3 & 4.4: Describe the short- & long-term consequences of alcohol consumption on the nervous system & liver, as well as social consequences of alcohol use. What is ALCOHOL? What are its EFFECTS on the human body? Alcohol (ethanol) is a recreational drug, which means that it is taken in social situations and has mild effects on the body if taken sparingly. However, alcohol is also a depressant, which means that it reduces nervous activity and slows bodily functions. Alcohol changes the structure of receptors of certain brain neurones, which affect neurotransmitter action potentials. If consumed in excess, it can heavily impair nervous transmission and lead to dehydration of the brain cells. Alcohol is broken down in hepatocytes by an enzyme called ethanol dehydrogenase, which converts ethanol to ethanoate, which can enter the Krebs cycle to produce ATP. This occurs in the liver. In the long-term, it can lead to scarring of liver tissue, called liver cirrhosis. Since the liver is used to detoxify the body, having it severely impaired will be fatal. Below is a summary of the effects of alcohol on the human body: Effect Notes Fatty liver hepatitis (short-term) Alcohol is used as an energy source by liver cells, allowing fat to accumulate around the liver. A common condition, but it is a precursor to liver cirrhosis. Liver cirrhosis (long-term) Liver cells become replaced with scar tissue, which impacts the liver‟s ability to produce bile salts, detoxify the blood and store glycogen. Impaired nervous transmission Since neurotransmitter activity slows down, reaction time increases and perception becomes distorted (e.g. blurry vision, reduced motor skills) due to the cerebrum and cerebellum being affected. Cancers Alcoholics have an increased risk of oral and throat cancers. Dehydration of brain cells Since the pituitary gland is affected, ADH release is suppressed. This means that less water is reabsorbed into the blood from the kidneys, leading to dehydration and „hangovers‟. Demyelination (loss of myelin sheath) of neurones also occur in the long-term, severely affecting brain activity. Increased risk of heart attack and stroke Even though alcohol is a depressant, it actually increases blood pressure. This is because it allows calcium ions to bind to blood vessels, causing them to constrict. This increases the chances of a coronary thrombosis rupture and ensuing heart attack or stroke. 90 What are the SOCIAL CONSEQUENCES of ALCOHOL ABUSE? Excess alcohol consumption is considered being over the recommended DAL (daily alcohol limit), which is considered to be no more than 2 – 3 for a woman and no more than 3 – 4 for a man, depending on body mass. One unit of alcohol can be calculated by using the following formula: ABV refers to Alcohol by Volume, which is a measure of alcoholic strength, as a percentage. So for e.g. a Heineken contains 330ml of beer. Working with an ABV of 5%, one bottle of Heineken would have 1.65 units of alcohol. A 200ml glass of Puncheon (75% ABV) would have 15 units of alcohol, well over the DAL (and even for the week!). Breathalyzer tests are able to test blood alcohol concentration, as the amount of alcohol in the breath is directly related to the concentration of alcohol in the blood. The liver is said to „break down‟ 1 unit of alcohol every hour that passes, using the enzyme ethanol dehydrogenase. Here are a few social consequences of exceeding DAL regularly: Effect Notes Car accidents Due to decreased reaction time, impaired motor skills and judgment, car accidents occur much more frequently with alcoholics at the wheel. This is why a „designated driver‟ is recommended to accompany a group. Violence Alcohol leads to a loss of inhibition, which can escalate altercations both in public, especially if both parties are drunk. This can also occur domestically. Intra-family issues and family breakdown If a family member is an alcoholic, they may exhibit very aggressive behaviour with other family members due to loss of inhibition and poor judgment. If the alcoholic is a breadwinner, they may be at risk of unemployment, throwing the family into financial turmoil. Neglect of children by parents may also occur if they are frequently drunk. Petty crime Due to reduced inhibition, committing petty crimes such as theft, harassment (sexual or otherwise) or vandalism may occur. Poor sexual intercourse decisions Though it is deemed immoral (and in a number of countries, illegal) to have sex with an individual who is drunk, reduced inhibition can lead to an individual having unprotected sex with someone undesirable, risking transfer of STI‟s and pregnancy. 91 4.5: Describe the effects of components of cigarette smoke on the respiratory & cardiovascular systems How is CIGARETTE SMOKING dangerous to your health? A familiar topic, cigarette smoking has been vastly proven to contribute to one of the most deadly conditions, COPD (Chronic Obstructive Pulmonary Disorder), where alveoli become enlarged due to elastin breakdown; mucussecreting goblet cells proliferate; and ciliated cells become destroyed. As a result, bacterial and viral infections (such as pneumonia and bronchitis) become more common; there is reduced oxygen supply to cells and increased risk of CHD and stroke occurs. Here‟s a rundown of how the four cigarette smoke components (tar, CO, nicotine and particulates) lead to one‟s health becoming compromised: Component Notes Tar and particulates These mostly contain carbon and lead to irritation in the airways. This irritation leads to white blood cells secreting an enzyme that breaks down the elastin of the alveoli. This creates large air spaces in the alveoli, separating the alveolar membranes from the capillaries, reducing surface area and capacity for gaseous exchange. This condition is known as EMPHYSEMA. The particulates can also result in excess mucus being produced due to proliferation of goblet cells in the trachea and bronchi. This is called HYPERPLASIA. Mucus is also a breeding ground for bacteria. Finally, ciliated cells become destroyed. These cells are known for catching bacteria-laden particles of dust and residue. Since these are gone, diseases like bronchitis become more common. Carbon monoxide (CO) Haemoglobin has a very high affinity for CO, which means that it will quicker take up CO than oxygen, leading to severely reduced oxygen uptake and reduced delivery to the heart and body cells. Due to the oxygen shortage, a hormone called erythropoietin is secreted, which increases red blood cell count. This may lead to an increase in blood viscosity („thicker‟ blood), increasing chance of ruptured blood clots and CHD. Nicotine Nicotine is very addictive. It also helps to constrict blood vessels, reducing lumen size of vessels and leading to increased risk of blood clot formation and CHD. Carcinogens These also contribute to risk of cancers, especially lung cancer. NOTE: Even being in an environment of smokers and inhaling the components poses a threat. This is commonly called second-hand smoke or PASSIVE SMOKING. 92 The Effect of NICOTINE on HEALTH Previously, we‟d established the following facts about nicotine that can affect health: 1. Nicotine is a stimulant. It closely resembles acetylcholine and tends to bind to ACh receptors in synapses. However, since acetylcholinesterase cannot break down nicotine, it stays bound for prolonged periods of time, causing the synapse to be overly excitatory. This can potentially increase heart rate (tachycardia) and blood pressure to the point of causing a stroke or a thrombosis. 2. Nicotine constricts blood vessels. In arteries, where atherosclerotic plaques have builta up, this greatly increases the possibility of a ruptured blood clot. This is because the reduced lumen size increases blood pressure and makes it less flexible. This ruptured clot can result in a heart attack or stroke. 3. The effect of nicotine on pregnant women‟s foetuses can cause much pre-natal harm. Nicotine causes constriction in the placental blood vessels, thus reducing exchange of nutrients and gases. It also delays excretion of waste from the foetus. All of this can lead to the foetus being undernourished or even miscarriage. 4. Nicotine may also constrict blood vessels and deprive oxygen flow to the extremities, such as the arms and legs. This leads to a reduced rate of respiration and prolonged fatigue. In worst case scenarios, especially if coupled with nerve damage from diabetes, it may lead to cell death and amputation. 5. Nicotine is highly addictive. People who regularly consume nicotine usually exhibit physical dependency on it. When suddenly stopped, it can produce a myriad of withdrawal symptoms, which may include anxiety, depression, cravings and irritability. 6. The nicotine from tobacco relaxes the valve between the oesophagus and stomach (lower oesophageal sphincter). This can allow stomach acid and juices, the chemicals that break down food in the stomach, to back up (reflux) into the oesophagus, which causes heartburn, peptic ulcers and nausea. 7. Nicotine changes chemical processes in the cells to increase insulin resistance. Glucose cannot bind to cell receptors to activate GLUT4 proteins to transport them through the membrane. This is a precursor of type II diabetes and results in a number of issues, including dehydration, nerve damage, cell death and coma. -