Body In Motion - Homeostasis PDF

Body in motion - Homeostasis L1 eV is used for energy in biochemical reactions instead of calories or joules because the number in joules will be extremely small Typical biochemical reactions involve energy changes...

Body in motion - Homeostasis L1 eV is used for energy in biochemical reactions instead of calories or joules because the number in joules will be extremely small Typical biochemical reactions involve energy changes of about 0.2eV Very many of them ae driven by 0.3 eV packets of energy Homeostasis involves Avoiding change caused by internal processes inherent to the body Avoiding change driven by external factors Many common diseases are failures of homeostasis Infection Diabetes melitus Hypertension Cancer Alzheimer’s disease Ageing (although debatable) There is a problem in maintaining order in homeostasis as ordered things tend to become disorganised over time Body in motion - Homeostasis 1  eg desk entropy - your desk becomes more disordered as you are looking for things ink spreading in water through a drop of ink. Transition from ordered state (clean water) to full glass becoming disinfected (full of ink) example of the ‘spreading ink’ problem within the body: oxygen spreading through the blood vessels. To fight back against this, the body has to expend energy just to ‘stand still’ to maintain its organisation against the action of the second law. The body cannot be a ‘closed system’ in which disorder inevitably decreases. To maintain homeostasis, the body has to expend energy to ‘stand still’ - to maintain its organisation against the action of the second law. So it cannot be a ‘closed system’ (in which disorder inevitably decreases) Sugars (glucose, fructose) are examples of plant-derived molecules we use for energy. Oxidising sugar gives a lot of energy Body in motion - Homeostasis 2  Energetics of typical biochemical reactions Reactions always run ‘downhill’ in energy terms*, but one reaction running a lot ‘downhill’ can be coupled to driving another reaction a bit uphill The conversion of ATP to ADP and Pi (downhill reaction) provides energy for the uphill reaction * strictly, ‘uphill’ in entropy terms, but ‘downhill in energy’ is good enough for almost all biology. n.b. in this context, the glucose is not providing the energy, but is simply acting as a substrate fo the reaction Body in motion - Homeostasis 3  In the conversion of glucose to fructose-1,6-bisphosphate, there are two phosphorylations First phosphorylation Second phosphorylation Why are we, oxidising sugar as we are, not on fire? Body in motion - Homeostasis 4  Typical biochemical reactions involve energy changes of about 0.2eV Very many of them are driven by 0.3eV ‘packets’ of energy donated by the energy carrier ATP (the difference appears as extra molecular motion, ie heat) But oxidising a molecule of glucose releases 29eV of energy, which is way too much Body in motion - Homeostasis 5  NADH is then converted to ATP at the end as it releases electrons, which travel down the electron transport chain, releasing energy. This energy is used to actively transport H+ ions against a concentration gradient and the H+ ions then diffuse back down Body in motion - Homeostasis 6  through the ATP synthase enzymes, producing ATP. Cyanide is poisonous because it interrupts this chain. Summary of the biochemistry Glucose is processed in a series of small steps, most of which allow the recovery of small amounts of energy Some steps pass this energy direct to ATP Some steps pass it to intermediate carriers such as NADH Metabolism is complicated because it has to be in small steps. These steps make lots of ATP molecules from the high energy molecules in food So… the result of all of this is that we can turn food into ‘packets’ of energy, in the form of ATP, that can bring 0.3eV each to drive reactions in cells (by coupling downhill ATP → ADP + Pi to an uphill reaction) L2 There are many examples of two compartments being separated by a membrane (this is common) Phase separation Body in motion - Homeostasis 7  Why does this happen? Water would rather interact with its own molecules than other molecules, which is why there is a phase separation between water and oil. The polar nature of water means that adjacent molecules can lower their free energy by interacting, +ve end of one to -ve middle of the other If you add non-polar molecules (pink), you stop water molecules adjacent to them from having polar interactions This stops them reaching their lowest energy state Systems want to run ‘downhill’ in terms of free energy*, so they minimise contact between polar and non-polar components by Body in motion - Homeostasis 8  grouping all the polar in one place (’phase’) In Entropy terms, which are the strictly correct way of looking at this, separating the phases increases entropy at the micro-level (by erasing all those ‘special’ places where polar bonding is messed up) enough to more than pay for the small decrease in entropy at the macro-level (two distinct layers you can see). But again, just thinking of minimizing free energy is fine for most biological thinking and few biologists talk about entropy. Key Concept: Micro-level entropy: When the system separates the phases, it frees the molecules from the constraints imposed by unfavorable polar-non-polar interactions. This increase in freedom at the micro-level leads to an increase in microscopic entropy. Macro-level entropy: On a larger, visible scale, the system looks more organized after phase separation because the molecules are grouped into two distinct phases (polar and non-polar). This makes the system appear more orderly, suggesting a decrease in macroscopic entropy. The overall change in entropy is positive because the increase in entropy at the micro-level (due to removing the disrupted polar-non-polar interactions) outweighs the decrease in entropy at the macro-level (where the system appears more organized after separating into two phases). Body in motion - Homeostasis 9  Large hydrophobic spaces are rare in the body (fat droplets in adipocytes are one example) Much more common is the use of very thin hydrophobic regions to make barriers between aqueous compartments Body in motion - Homeostasis 10  How can such a thin layer be stable? (not just coalesce into a droplet) There are molecules that are hydrophilic at one end and hydrophobic at the other (amphipathic) Body in motion - Homeostasis 11 Body in motion - Homeostasis 12  Water is attracted to hydrophilic substances, because they are polar, and they are not attracted to hydrophobic substances, because they ae non- polar. There is a problem with the basic arrangement of the phospholipid bilayer The tails pack so regularly the bilayers would be solid even at body temperature Therefore, the cell adds cholestrol to lipid bilayers to mess up their packing and stop them freezing at 37ºC (it essentially acts as an anti- freeze. Lipid bilayers themselves are selectively permeable: hydrophilic molecules cannot cross. Body in motion - Homeostasis 13  Water will not want to break off its bonds with other water molecules and enter a hydrophobic region However, some hydrophilic molecules need to get across the membrane: Food (eg glucose) Raw materials (eg amino acids) Waste products (eg urea) Ions Water (which can get through, but very slowly) Signals and information The membrane therefore needs selective channels Body in motion - Homeostasis 14  So far, we have four types of transport: (none of these mechanisms can create order on its own) Direct free diffusion Uniporter Body in motion - Homeostasis 15  Co-transporter (channels that can transport substances ‘together’ in the same direction) Antiporter (channels that can transport substances ‘together’ but in opposite directions) In all of these, net transport is down-gradient, and will reduce differences in concentration (like ink spreading in water again). They are all passive Body in motion - Homeostasis 16  Diagram of the phospholipid bilayer A ‘universal’ example of a maintained non-equilibrium is seen with Na+ and K+: Body in motion - Homeostasis 17 Body in motion - Homeostasis 18 Body in motion - Homeostasis 19  Summary Making and maintaining organization needs energy We turn high-energy foods into usable 0.3eV packets of energy (ATP) by set-by-step reaction schemes We use phospholipid membranes to separate compartments One use of ATP is to expel Na+ from cells and bring K+ in to create an electro-chemical gradient. Co-transporters can ‘parasitize’ this gradient to move solute uphill, at the expense of letting Na+ run back downhill. Thus cells can keep compartment contents distinct These transport processes are often useful drug targets. L3 A signal is a communication that conveys meaning (in science) Body in motion - Homeostasis 20  A “signal” and its meaning are defined from the point of view from the receiver The same signal can have different meanings to different receivers The amount of information that can be passed per unit time is the bandwidth High bandwidth is expensive This explains why long-distance messaging is done by passing simple signals, like yes no now from sender cells to receiver cells that already have the information necessary to know what to do (they have it by reading their genes) Signals can have different information content. For example: Body in motion - Homeostasis 21  ‘Please lift your foot off the throttle pedal, depress the clutch pedal, pull the gearstick to neutral*, release the clutch pedal, depress the accelerator for a moment, depress the clutch pedal, pull the gearstick into 2nd, and press the throttle pedal as you release the clutch’ ‘Please change from 3rd to 2nd gear’ ‘Now’ all can achieve the same thing, depending on what the listener already knows. Some biological systems have to carry vast amounts of information So, as far as possible, long-distance messaging is done by passing SIMPLE SIGNALS (‘Yes’, ‘No’, ‘Now’) from sender cells to receiver cells that already have the information necessary to know what to do (they have it by reading their genes) Body in motion - Homeostasis 22  The body’s use of SIMPLE signals to mediate communication between cells, tissue and organs is really useful to medicine. It means that if we can change the messages by making alterations to how well these simple signals are received, or by making simple signals of our own. (This is how most drugs work.) Classification of paths Autocrine signals - when a cell/group of cells signal to themselves Paracrine - one cell signalling to another cell Body in motion - Homeostasis 23  endocrine - used for long-distance signalling, reaching everywhere juxtacrine - direct contact between neighbouring cells How do signals get into cells? Sufficiently hydrophobic molecules can cross the membrane directly. The most famous class of these is steroids An example of how a steroid-mediated signal alters gene expression This kind of pathway is efficient, but relatively slow, and is often used for long-term things like sex determination, regulating puberty, menstrual cycles, stress and inflammation Use of receptors These are used for signals involving hydrophilic molecules (as they cannot directly travel through the membrane due to their hydrophilic nature) Body in motion - Homeostasis 24 Body in motion - Homeostasis 25 Body in motion - Homeostasis 26  Problem: What are the tradeoffs in signalling, between sensitivity, speed and economy? Sensitivity can be increased by amplification (despite a huge energy cost) eg here, think about the cost of putting all of that Ca2+ back, and Body in motion - Homeostasis 27  rebuilding all that PIP2! Ways of avoiding false signals from noise: Average over time (costs in speed of response) Average over a group of cells (but now we need some way of them communicating among themselves) Speed For high speed in both directions (on and off), we need rapid production of second messengers and activated effectors High energy costs Rapid destruction of the second messengers and activated effectors High energy costs Body in motion - Homeostasis 28  To achieve high-speed cellular responses (both activation and deactivation), there must be fast synthesis and rapid destruction of second messengers, which requires high energy expenditure. Body in motion - Homeostasis 29  The challenges of long-distance communication: Low speeds (eg brain to gonads to regulate ovulation) Slow as signals travel through the bloodstream Choice between producing lots of signals (eg to overcome dilution in the circulation) and using high sensitivity Generally, it is cheaper to produce small amounts of signal and a having the receiving cells sensitive Body in motion - Homeostasis 30  High-speed (eg brain to finger to control writing): ‘Pipe’ the signal down a direct high-speed path (see lectures on the nervous system). This avoids the dilution problem in hormonal movement Another advantage of nervous communication The idea of ‘wiring’ allows the same chemical signals to be used, and the same response systems to be used (‘contract a muscle’) to make the body do many different things, according to which ‘wires’ (nerves, axons) are activated and which muscles therefore fire. (another advantage of nervous communication) Body in motion - Homeostasis 31  Neurons and neurotransmitters For now Body in motion - Homeostasis 32  Hormones “broadcast” to every part of the body Neurons “text” their intended recipient only Both can result in inter-individual communication aswell L4 An example of an open-loop control is when you power a heater on low- medium-high. Thee is no loop to maintain the temperature at a certain point. However, an example of a closed loop control is when the heater turns on and then it reaches 20C and then it stops until the heat deceases again and then it reaches 20 again. Body in motion - Homeostasis 33  Homeostasis is a closed-loop control. This is required for holding steady in the face of unpredictable change. The body has to keep its proper internal environment in the face of both internal and external changes; Internal wake-sleep resting-active standing-recumbant Body in motion - Homeostasis 34  pregnancy External: warm-cold injured by animal or falling tree branch drought/famine - plenty Body in motion - Homeostasis 35  This is a bit like Zeno’s paradox, except it is not an illusion caused by faulty thinking In homeostasis, we have proportional control & integrative control. Proportional control - looks at how big the error is integrative control - looks at the integral of the error with respect to time Proportional control gets weaker as the error decreases. This means that as the system approaches the baseline, the correction becomes so small that it may not be enough to bring the system all the way to the target,. This leaves a small residual error. Body in motion - Homeostasis 36  So far, we have covered homeostasis through a reactive measure. Body in motion - Homeostasis 37  A parameter is normal → Something pulls the parameter up or down → A response is initiated to restore the parameter However, if the parameter is really critical to health, allowing it to run away in the first place may be a very bad idea - there are some times when you cannot afford to have the system play catch-up. This explains anticipative physiological changes, which prepare the body for running or fighting. However, these are unhelpful for ‘modern’ scares eg driving that makes no physiological demands. Chronic activation of the ‘fight or flight’ pathway is dangerous Can lead to myocardial infarction Examples of anticipatory mechanisms Eating - extra saliva production for digestion of starch Female sexual response - enhanced mucus secretion to prevent damage Anticipatory changes almost always involve the brain doing some pattern- recognition and 'reading' the short-term future. Body in motion - Homeostasis 38  In all mammals, anticipatory homeostasis is common in the three great drives, which physiologists have long called the thee Fs Fleeing Fighting Mating L5 Failures of homeostasis Damage to effectors eg traumatic breach of barriers integument and of blood vessels, allowing fluids to be where they should not be. The main treatment at this trivial or more serious levels, is to clean, then restore. eg renal failure. Main treatment: renal dialysis. This uses an external machine to replace the functions of the kidney (to an imperfect extent) damage to pacemaker → treatment: artificial pacemaker Doctors rarely repair these defects, but instead they produce new artificial mechanisms to fix these. Damage to control systems (here, we normally use a drug that mimics a missing signal or one that blocks a pathway inappropriately active) Congenital absence of a regulator (eg leptin > obesity) Damage to a critical feedback system (eg Addison’s disease - no signals from adrenal cortex) Inappropriate activation of a homeostatic signal (eg allergy) Cell wrongly interpreting valid signals (eg neoplasia) Body in motion - Homeostasis 39  Positive feedback: Body in motion - Homeostasis 40  many drugs have side effects Body in motion - Homeostasis 41  Take-home messages from this week: Homeostasis is essential to life: it can be achieved only with the expenditure of energy, and is indeed the main consumer of the human energy budget Homeostasis is usually achieved using feedback loops, featuring proportional, integrative and sometimes differential control. It may be anticipative. Many types of diseases are failures in some aspect of homeostasis, either in control systems of effectors When confronted with a failure in an effector, doctors typically turn to artificial substitute effectors. These seldom actually fix the underlying problem, although they may allow the body to fix itself (healing under a bandage) Body in motion - Homeostasis 42