Physiology Lecture Notes PDF

Physiology, its tasks Physiology is a fundamental science of biology that studies all the life processes in the organism, the functions of cells, tissues, organs, principles and mechanisms of their regulation.  Life processes in the organism:...

Physiology, its tasks Physiology is a fundamental science of biology that studies all the life processes in the organism, the functions of cells, tissues, organs, principles and mechanisms of their regulation.  Life processes in the organism: the functioning of the organism – it means survival, growth, reproduction, aging...  Functions of individual tissues, organs, cells: constant specific activity to maintain life processes even in changing external and internal environmental conditions  Regulation is a sequence of processes for the realization of all functions Physiology is the theoretical basis in all disciplines of veterinary medicine and human medicine. It has a close connection with morphology and anatomy (the study of the structure of organisms), cytology (the study of the structure and function of cells), biochemistry (all life processes depend on chemical reactions), biophysics (necessary to understand processes in organisms such as electrical conduction, fluid dynamics…), zoology and ecology (the relations of organisms to one another and to their physical surroundings). We cannot understand organ, tissue and cell functions if we do not know their macroscopic and microscopic structure. The aim of animal physiology:  Both to explore and understand life processes: Autonomic – those processes we cannot control (blood pressure, peristalsis in digestive system, sweating etc.) Somatic – the processes we can control (body movements, skeletal muscles, eye blinking) Sensory – hearing, seeing, feeling etc. Psychic – emotions, anger, fear, satisfaction etc.  And search for ways how to use surrounding enviromental factors for enriching functional body reserves and increase animal productivity1 The internal environment of an organism Multicellular organisms are composed of various types of cells: ✓ They have specific functions ✓ Cells with similar properties assemble to form tissues ✓ An organ is composed of several types of tissue ✓ Organs cooperate to form organ systems ✓ Organ systems cooperate to perform body functions to maximize the benefit to the entire organism Everything is tightly coupled and regulated. 1 Frankenstein bull has become a reality – Belgium blue bull, looks like a real muscle balloon. This bull has approximately 40% extra muscle mass. The animals of this breed gain the weight very rapidly. One thing that is not being widely popularized is that these are genetically modified animals, they have blocked protein myostatin which regulates the growth of muscles. The rapid muscle growth causes many health problems. Calves have enlarged tongues (tongue is a muscle) and they have foot edema. They have problems with movements and often that leads to early and painful death… 1  Homeostasis The relative constancy of an organism's structure, genetics, and internal environment and the mechanisms that maintain it is called homeostasis.  This constancy is understood by structural, genetic and constant internal environment.  Structural homeostasis is aimed at preserving the body's anatomical integrity and functional abilities. It is mostly provided by sensory systems.  Genetic homeostasis is aimed at preserving the genetic individuality of the organism. It is provided by the immune system and immune tissues.  Homeostasis of the internal environment is ensured by all organs and tissues, maintaining the necessary amount of nutrients and substances, gases (CO2, O2) necessary for plastic processes and reducing the concentration of the end products of metabolism.  All autonomic structures (those that do not obey the will) of the body participate in the maintenance of homeostasis of the internal environment. Each of these variables (e.g., CO2, O2, body temperature, the pH, or the Na+, Ca2+ and glucose concentrations) is controlled by a separate “homeostat” (or regulator), which, together, maintain life. Homeostats are energy consuming physiological https://www.istockphoto.com/vector/homeostasis-as-biological- mechanism. state-with-temperature-regulation-outline-diagram- Fluctuations in the external environment cause gm1334390450-416526650 fluctuations in the internal environment, but they are regulated by homeostasis mechanisms. Parameters of homeostasis of the internal environment  All cells are in contact with the body’s internal environment, which is made up circulating body fluids.  Therefore, as parameters of internal environment homeostasis, it is accepted to consider indicators of body fluids such as: ◦ pH (7,35-7,45) (acid-base balance in blood) ◦ different salt concentrations (osmotic pressure) (6,8-7 kPa) ◦ dissolved proteins (oncotic pressure or colloid osmotic) ◦ temperature ◦ fluid volume (hematocrit) ◦ blood glucose, etc. Homeostasis types Generally, there are three types of homeostatic regulation in the body, which are: 1. Thermoregulation 2. Chemical regulation 3. Osmoregulation 1. Thermoregulation. Thermoregulation is the process occurring inside the body that is responsible for maintaining the core temperature of the body. Thermoregulation works by the negative feedback loop where once the body temperature is either increased or decreased beyond its normal temperature, it is brought back to normal. 2  Different homeostatic processes like sweating, dilation of blood vessels counteract the increased body temperature, whereas processes like contraction of blood vessels, and breakdown of adipose tissue to produce heat prevent the decreased body temperature. The process of thermoregulation is maintained by organs like skin and adipose tissue of the integumentary system and the hypothalamus of the brain. 2. Chemical regulation. Chemical regulation is the process of balancing the concentration of chemicals like glucose, calcium, acid-base balance, carbon dioxide, etc. in the body by producing hormones. During this process, the concentration of hormones like insulin increases when the blood sugar level increases in order to bring the level back to normal. A similar process is observed in the respiratory system, where the rate of breathing increases as the concentration of carbon dioxide increases. 3. Osmoregulation. Osmoregulation is the process of maintaining a constant osmotic pressure inside the body by balancing the concentration of fluids and salts. During this process, excess water or ions or other molecules like urea are removed from the body to maintain the osmotic balance. One classic example of this process is the removal of excess water and ions out of the blood in the form of urine to maintain the osmotic pressure of the blood. The rennin-angiotensin system and other hormones like antidiuretic hormones act as a messenger for the electrolytic regulation system of the body. https://pmgbiology.files.wordpress.com/2015/02/32-06.gif Homeostasis – fluid compartments Equilibrium maintained by osmoregulation. Water constitutes ~60-70% of bodyweight. An individual mammalian cell contains approximately 80% water. Transcellular fluid (usually a low percentage but variable amount) 40% 20% 15% 5% https://www.lecturio.com/concepts/body-fluid-compartments/ 3 Intracellular fluid (ICF) (40%) ◦ Lies inside the cells (cytoplasm) All water that is not in cells is considered to be extracellular fluid (ECF), or outside the cells.  Extracellular fluid (ECF) (20%) ◦ Lies outside the cells ◦ Interstitial fluid (ISF) (outside capillaries, surrounds https://quizlet.com/545970261/chapter-27-anatomy- and-physiology-flash-cards/ the cells) ◦ Intravascular fluid (IVF) (plasma volume) ◦ Transcellular (TCF) (in body cavities, e.g., intraocular fluid, cerebrospinal fluid, synovial fluid, bile, fluids of the digestive tract) The most plentiful transcellular fluid is in the digestive tract, and its amount is greatest in ruminants because of the stomach compartments associated with fermentation. https://faculty.ksu.edu.sa/sites/default/files/fluid_imbalance_2.pdf ❖ Lymph forms the interstitial fluid. Thus, lymph is an extracellular interstitial fluid. Homeostasis mechanisms All have at least 3 components: ◦ Receptor – senses environmental stimuli  Chemoreceptors ◦ Integrating center – signals to effectors  Hypothalamus ◦ Effector – responds to stimuli  Organs  Muscles A sensor or receptor detects changes in the internal or external environment. An example is peripheral chemoreceptors, which detect changes in blood pH. The integrating center or control center receives information from the sensors and initiates the response to maintain homeostasis. The most important example is the hypothalamus, a region of the brain that controls everything from body temperature to heart rate, blood pressure, satiety (fullness), and circadian rhythms (sleep and wake cycles). An effector is any organ or tissue that receives information from the integrating center and acts to bring about the changes needed to maintain homeostasis. One example is the kidney, which retains water if blood pressure is too low. Feedback loops The sensors, integrating center, and effectors are the basic components of every homeostatic response. Positive and negative feedback are more complicated mechanisms that enable these three basic components to maintain homeostasis for more complex physiological processes.  Positive feedback loop  Negative feedback loop 4  Feedback loops – positive Positive feedback is a mechanism in which an output is enhanced in order to maintain homeostasis. Positive feedback mechanisms are designed to accelerate or enhance the output created by a stimulus that has already been activated. Positive feedback mechanisms are designed to push levels out of normal ranges. To achieve this, a series of events initiates a cascading process that builds to increase the effect of the stimulus. This process can be beneficial but is rarely used because it may become uncontrollable. A positive feedback example is blood platelet accumulation and aggregation, which in turn causes blood clotting in response to an injury of the blood vessels. Another example of a positive feedback loop comes into play during childbirth. In childbirth, the baby's head presses on the cervix—the bottom of the uterus, through which the baby must emerge—and activates neurons to the brain. The neurons send a signal that leads to release of the hormone oxytocin from the pituitary gland. Oxytocin increases uterine contractions, and thus pressure on the cervix. This causes the release of even more oxytocin and produces even stronger contractions. This positive feedback loop continues until the baby is born. An uncontrolled example: too much blood platelet aggregation in many places at once may cause an uncontrolled cascade of blood clotting throughout the body, not just locally like in skin wounds. Feedback loops – negative Negative feedback mechanisms reduce output or activity to return an organ or system to its normal range of functioning. Regulation of blood pressure is an example of negative feedback. Blood vessels have sensors called baroreceptors that detect if blood pressure is too high or too low and send a signal to the hypothalamus. The hypothalamus then sends a message to the heart, blood vessels, and kidneys, which act as effectors in blood pressure regulation. If blood pressure is too high, the heart rate decreases as the blood vessels increase in diameter https://doctorlib.info/physiology/medical-physiology-molecular/24.html (vasodilation), while the kidneys retain less water. These changes would cause the blood pressure to return to its normal range. The process reverses when blood pressure decreases, causing blood vessels to constrict and the kidney to increase water retention. What happens if these feedback loops fail? Disease is any failure of normal physiological function that leads to negative symptoms. While disease is often a result of infection or injury, most diseases involve the disruption of normal homeostasis. Anything that prevents positive or negative feedback from working correctly could lead to disease if the mechanisms of disruption become strong enough. https://www.chegg.com/learn/topic/homeostasis-of-internal- environment-regulation 5  Aging is a general example of disease as a result of homeostatic imbalance. As an organism ages, weakening of feedback loops gradually results in an unstable internal environment. This lack of homeostasis increases the risk for illness and is responsible for the physical changes associated with aging. Heart failure is the result of negative feedback mechanisms that become overwhelmed, allowing destructive positive feedback mechanisms to compensate for the failed feedback mechanisms. This leads to high blood pressure and enlargement of the heart, which eventually becomes too stiff to pump blood effectively, resulting in heart failure. Severe heart failure can be fatal. Control and regulation of research in physiology in Latvia  Is controlled and regulated by: ✓ «Dzīvnieku aizsardzības likums» (Animal Protection Act) ✓ MK noteikumi Nr. 1 (08.01.2019.) (Regulations of The Cabinet of Ministers No.1 «Protection of animals used for scientific purposes» ✓ Food and Veterinary Service ✓ LBTU Animal Welfare and Protection Ethics Council  Ethical attitude is a sign of humanity!!! Animal Protection Act applies all animal owners, breeders, people who use animals as a tourist attraction, farmers, zoos etc. Forbids any type of cruel treatment of animals – unnecessary killing, torture, taunting, keeping animals in unsuitable conditions etc. Regulation No.1 Applies to breeders, suppliers and users of experimental animals. It describes the procedures for issuing and cancelling an experimental project authorization to the responsible person. It also describes the procedures by which experimental project authorization shall be issued, amended, renewed or cancelled. It outlines the welfare requirements for the acquisition, breeding, marking, keeping, care, supplying and use of experimental animals. The procedures for the assessment of experimental projects. It states the requirements for premises, facilities, inventory and equipment of breeders, suppliers and users. This regulation also outlines ethical methods of killing experimental animals and it also describes the procedures by which documents are submitted in order to receive authorization for an experiment. Food and Veterinary Service responsible for food and veterinary surveillance in Latvia. Oversee food safety and animal welfare; biosecurity. Perform inspections of animal holdings, slaughterhouses, clinics, food processing plants, restaurants etc. LBTU Animal Welfare and Protection Ethics Council. Established by our university in 2015, in accordance with Regulation No. 1 and by decree of the Rector. So, their function is to act as a consulting institution for breeders, suppliers and users of experimental animals. They also evaluate research projects to make sure ethical treatment of experimental animals is observed. 6  The cell – basic components All cells have a minimum set of components in order to function properly. ✓ Cell membrane2 – surrounding the rest of the cell. Consists of a phospholipid bilayer, which has many types of protein inserted. It is a sort of a liquid mosaic. ✓ Cytoplasm – composed of the cytosol. Consists of water and dissolved ions and molecules. https://www.britannica.com/science/membrane-biology ✓ Organelles – the equivalent of organs in the cell, each with a specific function. Biological membrane structure  Phospholipid bilayer (i.e., double layer) ◦ Formed by phospholipids ◦ Electrically charged (polar) head – hydrophilic ◦ Two non-polar tails - hydrophobic Membrane’s phospholipids allow water to pass through one side (hydrophilic) but from the other side it repulses water (hydrophobic)  Proteins (channels, receptors, etc.)  Cholesterol – which stabilize the bilayer by forming weak chemical bonds to the phospholipids. This makes the cell https://www.istockphoto.com/vector/phospholipid-or- phosphatides-lipids-microscopical-structure-outline- membrane stronger, but also less liquid diagram-gm1353539264- 428607949?phrase=phospholipid&searchscope=image%2C  Glycolipids, glycoproteins, etc. film In both layers the hydrohilic heads will be facing the surrounding liquid outside and inside of the cell (extracellular fluid and cytoplasm, respectively). The hydrophobic tails two opposite layers will be facing each other. They form a hydrophobic layer within the membrane. https://conductscience.com/biological-membrane/ 2 A biological membrane, biomembrane or cell membrane is a selectively permeable membrane that separates cell from the external environment or creates intracellular compartments. 7  Biologic membrane (BM) functions Separates the IC fluid of each cell from the EC medium.  Support function – forms the skeleton of each cell  Barrier function – prevents the penetration of harmful substances further into the cell  Biopotential genesis function because BM is electrically polarized  Function of energy transformation – mainly in mitochondria  Enzymatic function – BM is like a “harbor/port” for part for a part of enzymes (membranal digestion in digestive tract)  Receptor function – there are specific places – receptors that respond to to neurotransmitters (epinephrine, acetylcholine), ensuring performance of a reflex  Selective permeability of the BM determines the unequal distribution of ions inside and outside the cell!!! The main cations of EC fluid are Na+ and Ca2+ but anions Cl- and HCO3-, but the main cations of IC fluid are K+ and Mg+ (Na2+ is ina small amount) but anions PO43- So, there are mainly Na ions outside the cell, but K ions inside the cell. The membrane is selectively permeable!!! Membrane potential The membrane potential is the voltage or electrical potential caused by the separation of oppositely charged particles. Typically, the outside of the cell is slightly more positive than the inside of the cell as a result of the sodium-potassium pump and because sodium diffuses into the cell more slowly than potassium diffuses out. Clinical Anatomy and Physiology for Veterinary Technicians Resting membrane potential Charged particles (ions) exist within the IC and EC environments of all tissues. The amount, type, and distribution of these ions are important in maintaining cellular homeostasis. BM is more permeable to some of these molecules than to others. This difference in permeability leads to changes in the distribution of the charged particles on either side of the cell membrane, which, in turn, forms a membrane potential or voltage. Although many ions are contained within the intracellular and extracellular fluids, the principal ions involved in maintaining membrane potential are K+ and Na+. Normally more K+ inside the cell than outside, and therefore K+ moves out of the cell via diffusion. Na+ is more concentrated outside the cell than inside but, unlike K+, it cannot enter the cell easily. The influx of Na+ is lower than the outflow of K+. In addition, for every cycle of active transport, 3 Na+ molecules exit the cell for every 2 K+ molecules that are retrieved. Thus, both active and passive membrane processes help to place more + charged ions on the outside of the cell than on the inside. Some specialized cells, such as muscle cells, owe their ability to contract to changes in membrane potential. Neurons transfer signals when the resting membrane potential changes. 8  The level of resting membrane potential of the biological membrane If only K+ was diffusing, then the equilibrium potential of K+ would be -90mV. Since Na+ diffuses freely within the cell even at rest, the resting membrane potential is:  For nerve cells (neurons) ~ -70 mV  For skeletal muscles ~ -90 mV  For smooth muscle fibres ~-60 mV The minus sign indicates that the cell is https://twitter.com/UsmleAid/status/6554 negative along the inner layer of the cell 69062944763905 membrane relative to the outer cell surface. https://socratic.org/questions/why-is-the-resting- potential-of-a-cell-70mv-and-not-70mv Distribution and transfer of substances through the BM From EC fluid, cells (IC fluid) selectively receive substances important for life support and plasticity (oxygen, glucose, amino acids, fatty acids, ions, etc.) but get rid of metabolic end products. The permeability of a BM depends on the substance: ✓ size ✓ solubility ✓ charge Small molecules cross without difficulty, especially if they are lipid soluble. Molecular gases cross very rapidly. Larger molecules cross without difficulty only if they are lipid soluble. To small uncharged polar molecules, the BM is largely permeable but to large uncharged polar molecules the BM https://www.abpischools.org.uk/topics/cell-biology/passive- transport-across-cell-membranes/ is largely impermeable. The exchange of substances through the BM takes place in two ways:  Passive transport – substances move through the BM without consuming cell energy, but using other forms of energy. In the case of electroneutral molecules, the process is driven by the concentration gradient, but in the case of ions, also by the electrical gradient (potential). This is how osmosis, diffusion, filtration occurs.  Active transport of substances – substances move through the BM using energy (ATP). A molecule or ion is transported through the membrane against its electrical and concentration (electrochemical) gradient. Energy can be obtained: ATP hydrolysis, light absorption, oxidation processes, etc. 9  Passive transport Driving force – concentration gradient and electrical forces.  Four types: ◦ Diffusion (simple diffusion through the phospholipid bilayer; facilitated diffusion through a nonspecific transporter or through a specific transporter) ◦ Osmosis through the lipid bilayer and an aquaporin3 ◦ Filtration ◦ Passive conduction along electrical gradient https://microbenotes.com/passive-transport/ Diffusion is he movement of a molecule down a concentration gradient, from an area of its high concentration to an area of its low concentration. This process is passive, i.e., it requires no input of additional energy; the concentration gradient alone is enough to drive the process. This process takes place as long as there is a difference in the concentration of substances on both sides of the BM. Simple" or "passive" diffusion occurs by one main method. The molecules just brutally force themselves across the lipid bilayer, driven purely by their concentration gradient. This process is obviously governed by simple factors such as membrane thickness, concentration gradient, surface area, molecule size, temperature (velocity of kinetic molecular motion) and lipid solubility. Molecular gases cross very rapidly Small molecules cross without difficulty, especially if they are lipid soluble Larger molecules cross without difficulty only if they are lipid soluble For charged molecules (e.g., ions), the lipid bilayer is virtually impermeable Gases like molecular oxygen and carbon dioxide diffuse across the membrane as if it wasn't even there, at a rate of 2-3 mm/sec. Gases don't even need to be particularly lipid-soluble, but it helps (hence the 50% faster rate of diffusion seen with CO2). The next order of magnitude is occupied by small molecules like water, and larger lipid-soluble molecules like alcohol and steroids. Water is strongly polar but has the advantage of having a massive concentration which allows it to force its way across the lipid bilayer in answer to osmotic shifts. The lipid-soluble molecules benefit from their high lipophilicity and are able to penetrate the barrier easily in spite of their comparatively larger size (eg., ethanol actually diffuses faster than water). The middle diffusion tier (we might call it "cross with difficulty") are substances which are either significantly larger or not particularly lipophilic. This group includes urea, various small- molecule drugs, peptides and glycerol. Relying on passive diffusion for their transport is probably unreasonable if rapid entry into the cells is therapeutically required, but - left to marinade - they will eventually make their way in. One clinically relevant example of this is the tendency of urea to gradually infiltrate the brain of a chronic renal failure patient, where it produces osmotic cerebral oedema by failing to rapidly equilibrate with extracellular fluid following dialysis. 3 Water channels 10  Lastly, highly charged small molecules and ions have a lot of difficulties crossing the membrane. The rate of diffusion for charged sodium and potassium ions is fifteen orders of magnitude (one quadrillion) times slower than for uncharged molecular gases. Working backwards from the diffusion coefficient, these ions take tens of thousands of seconds (i.e., hours) to cross a 5 nm lipid bilayer. Some sort of active help is therefore essential to mediate their transport. All of these numbers and measurements are relevant mainly to some sort of idealized model of a purified deproteinated lipid bilayer. In real life, ions water and small molecules can also make their way across the membrane using protein channels as conduits. As with direct-through-the-bilayer diffusion, this is a purely passive process - i.e., nothing is done to help the solutes get across the membrane. To sum up: simple diffusion – molecules with good solubility in lipids (diffuses O2, CO2, drugs, steroid hormones…) Simple diffusion occurs relatively slower. Influenced by concentration, solubility, temperature, size of molecules, distance. 1. The greater the difference in concentration, the greater the rate of diffusion. 2. The permeability of the membrane to the substance. The more permeable the membrane is to a substance, the more rapidly the substance can diffuse down its concentration gradient. 3. Temperature. Generally, as temperatures increase, the higher kinetic energy of molecules will increase diffusion rates. Permeability may also be affected, generally increasing as temperature rises. 4. The molecular weight of the substance. Lighter molecules such as O2 and CO2 bounce farther on collision than do heavier molecules. 5. The distance through which diffusion must take place. The greater the diffusion barrier thickness, the slower the rate of diffusion. Accordingly, membranes across which diffusing particles must travel are normally relatively thin, such as the membranes separating the air and blood in vertebrate lungs. One of the most important aspects of diffusion to keep in mind is how extraordinarily slow the process is because of its inherent randomness and molecular scale. For example, oxygen moving only by diffusion through a nostril would take many years to reach equilibrium within a large airbreathing animal. Thus, an animal that needs to transport molecules such as oxygen and hormones over large distances cannot rely on diffusion. https://quizlet.com/594908596/module-1-lecture-1-dr-fuller-homeostasis-flash-cards/ Facilitated diffusion – molecules with poor solubility in lipids. These molecules can pass through the BM along a concentration gradient, but with the assistance of an integral protein or passive carrier protein. Occurs faster than passive diffusion. Examples of substances that move into the cell by facilitated diffusion through gated channels are sodium ions (Na+), potassium ions (K+) and chloride ions (Cl-), glucose, amino acids. Influenced by: substance concentration, temperature, the presence of carrier proteins. All of the above-mentioned passive diffusion numbers and measurements are relevant mainly to some sort of idealised model of a purified deproteinated lipid bilayer. In real life, ions water and small molecules can also make their way across the membrane using protein channels as conduits. As with direct-through-the-bilayer diffusion, this is a purely passive process - i.e., nothing is done to help the solutes get across the membrane. This is facilitated diffusion. 11  "Facilitated diffusion requires interaction of a carrier protein. The carrier protein aids passage of the molecules or ions through the membrane by binding chemically with them and shuttling them through the membrane in this form." The rate of this is obviously going to be quite variable from cell to cell, depending on the expression of porins and channels on its surface. However, unlike simple passive diffusion, facilitated diffusion usually has some practical limits to its capacity, which is basically related to the rate at which those molecules can percolate through those channels. That is to say, as concentration gradient increases, so the rate of passive diffusion increases, but facilitated diffusion hits a wall beyond which no additional changes in concentration can produce any increase in the membrane permeability. The proteins which permit facilitated diffusion can exert some degree of control over what precisely is permitted entry into the cell; this is accomplished by a combination of pore size and charge selectivity. The upshot of this is that usually, diffusion-facilitating protein channels are strongly selective for a specific molecule. The diffusion of ions across these channels usually needs to be regulated in some way in order for the diffusion to be useful in some meaningful sense. Concentration gradients are there to be used for various cellular projects, and so it would be pointless to just allow ions to equilibrate on either side of the membrane. Thus, ion channels are usually gated. Gating can be by effects of some substance the binding of which triggers the protein to open or close (ligand gating) or it can be managed by changes in membrane potential (voltage-gating). https://www.sciencefacts.net/simple-diffusion-vs-facilitated-diffusion.html Osmosis is provided by the difference in the osmotic pressure (concentration of dissolved salts) gradient on both sides of the BM. !!! This means that in order to equalize the concentration of dissolved salts on both sides of the BM, the solvent (usually H2O) passes through the BM in the direction from the side with the lowest to the highest concentration of salts. Occurs as long as there is a difference in osmotic pressure between the IC and EC environment. Clinical Anatomy and Physiology 12   Water passes through the BM to the side where the concentration of dissolved salts is higher, until equilibrium is reached.  E.g., if the osmolarity (concentration of dissolved salts, e.g., NaCl) in the EC environment is higher than in IC environment, then the cell loses fluid (also volume), but if the osmolarity is lower, the cell is filled with water, swells and can rupture. https://www.thoughtco.com/osmotic-pressure-and-tonicity-3975927 Filtration is provided by the difference in hydrostatic pressure (fluid pressure on the membrane) Efferent Afferent gradient on both sides of the BM. arteriole arteriole E.g., see the filtration process in the kidney (glomerulus) In animals, hydrostatic pressure is blood pressure and is generated by the pumping heart. Blood, as it circulates in the body, is forced through vessels and small capillaries. Small molecules and cells may be pushed through, but large cells may not. One of the best examples of filtration in animals is evident in the kidney, https://quizlet.com/fr/403804648/cnm11-06-urine-formation-glomerular- where blood is filtered through specialized capillaries in filtration-renal-autoregulation-and-colloid-osmotic-pressure-flash-cards/ the process of making urine.  Passive conduction along electrical gradient is provided by the electrical potential gradient on both sides of the cell membrane.  Due to attraction of negatively and positively charged particles (ions), ion movement occurs through the BM. Ions that can permeate the membrane also conduct passively along their electrical gradient. Movement of ions (electrically nd Animal Physiology from Genes to Organisms 2 Edition charged particles that have either lost or gained an electron) is also affected by their electrical charge. Like charges (those with the same kind of charge) repel each other, whereas opposite charges attract each other. The positively charged ions (cations) tend to move toward the more negatively charged area, whereas the negatively charged ions (anions) tend to move toward the more positively charged area. A difference in charge between two adjacent areas thus produces an electrical gradient that passively induces ion movement—a process called conduction. When an electrical gradient exists between the ICF and ECF, only ions that can permeate the plasma membrane can conduct down this gradient. The simultaneous existence of an electrical gradient and concentration (chemical) gradient for a particular ion is called an electrochemical gradient. You will frequently find that ion movement is called “diffusion,” but this is improper terminology when charge differences are causing movement. Recall that diffusion is based on random molecular motions, and is very slow. Ion conduction, in contrast, is much faster because of charge interaction, which is a strong directional force (think about how fast two magnets can move toward each other, an analogous situation). 13  Active transport  Transport ions against the concentration gradient  Active transport maintains unequal concentrations of ions between the ECF and cytosol. ◦ Essential for electrical properties of cells  Occurs via carrier proteins ◦ Specific ◦ Limited capacity https://en.m.wikipedia.org/wiki/Transport_protein ◦ Subject to competition Large, poorly lipid soluble molecules such as proteins, glucose, and amino acids cannot cross the plasma membrane on their own no matter what forces are acting on them. Most small, charged molecules (ions) have the same property. This impermeability ensures that the large intracellular proteins and critical ions cannot escape from the cell. It is important that these molecules remain in the cell where they belong and can carry out their functions. However, because of this impermeability, the cell must provide mechanisms for deliberately transporting some of these types of molecules into or out of the cell when it is necessary. For example, the cell must usher into the cell essential nutrients, such as glucose for energy and amino acids for the synthesis of proteins, and transport out of the cell metabolic wastes and secretory products, such as water-soluble protein hormones and digestive enzymes. Some ions must enter or leave the cell in, for example, signaling processes such as those of neurons. 1. Primary active transport is the process of using chemical energy (usually stored in ATP) to facilitate the transport of ions from one side of the membrane to the other (often against concentration gradient). In this mechanism protein (carrier protein) at the same time is: 1) an enzyme – it catalyzes the hydrolysis of ATP so that the energy obtained can be used for ion pumping; 2) a pump (carrier) Transport of molecules usually against their concentration gradient. E.g., Na+/K+ pump – it exchanges 200 Na+ out of the cell and 130 K+ in https://biology.stackexchange.com/qu to the cell through the BM in one second, making the IC environment estions/54947/are-na-k-active-pumps- and-k-na-leak-channels-same-as- more negative (-)!!! given-in-the-figure 2. Secondary active transport. The reason it is called secondary is that instead of direct ATP- burning chemical energy, this mode of transport uses a concentration gradient which has already been created by another primary active transport system. It this way, the transfer of a substance or ion is coupled with the transfer of other substances. In short, proteins involved in this mode of transport are usually referred to as "exchangers" rather than pumps. This group includes co-transporters and counter-transporters. In co-transport, the concentration gradient pushing an ion across a cell membrane is used to pull another molecule in the same direction (eg., sodium and glucose co-transport into the cell). Counter-transport is the exchange of molecules, where the concentration gradient of one participant is used to move the other in the opposite direction (and often against its own concentration gradient).  Co-transport, Na+ with glucose, but at least 2 factors must be met: 1. If Na+ is bound to a specific carrier protein SGLT 2. If there is a Na+ electrochemical gradient – which is ensured by the Na+/K+ pump, keeping the Na+ concentration in the cell low. 14  https://slideplayer.es/slide/15959007/ Counter-transport: 1) Sodium-calcium counter-transport occurs through all or almost all cell membranes, with sodium ions moving to the interior and calcium ions to the exterior, both bound to the same transport protein in a counter-transport mode. This is in addition to primary active transport of calcium that occurs in some cells. https://doctorlib.info/physiology/textbook-medical-physiology/4.html 2) Sodium-hydrogen counter-transport occurs in several tissues. An especially important example is in the proximal tubules of the kidneys, where sodium ions move from the lumen of the tubule to the interior of the tubular cell, while hydrogen ions are counter-transported into the tubule lumen. As a mechanism for concentrating hydrogen ions, counter-transport is not nearly as powerful as the primary active transport of hydrogen ions that occurs in the more distal renal tubules, but it can transport extremely large numbers of hydrogen ions, thus making it a key to hydrogen ion control in the body fluids. There are different types of carrier proteins in active transport: ◦ Uniporter – transports only one ion or type of molecule ◦ Symporter (co-transporter) – transports all substances in the same direction ◦ Antiporter (counter-transporter) – transports different substances in opposite directions Uniport: Glucose transporter (GLUT) - facilitated diffusion of glucose Symport: the coordinated uptake of glucose and Na+ is an example of symport, the transport of 2 molecules in the https://kaiserscience.wordpress.com/biology-the-living-environment/cells/active- same direction. transport-across-cell-membranes/ Antiport: sodium calcium exchanger, Na/K pump 15  Vesicle transport (cytosis) Large particles are transferred between the ICF and ECF by being wrapped in a membrane- enclosed vesicle, a process known as vesicular transport. Like active transport, cytosis requires ATP and is therefore considered an active transport.  Two types: endocytosis (going into the cell) and exocytosis (going out of the cell) ◦ Endocytosis: enables large particles, liquid substances, and even entire cells to be taken into a cell by engulfing them (phagocytosis – cell engulfs solid substances; pinocytosis – engulfs liquid substances; receptor- mediated endocytosis – specialized protein receptors bind to ligands https://microbenotes.com/endocytosis-definition-process-and-types-with- examples/ specific to receptors. Example: catecholamine neurotransmitter reuptake. ◦ Exocytosis: excretion of waste products and secretion of manufactured substances; these substances are packaged in secretory vesicles, which fuse with cell membrane; contents are ejected to the extracellular space. Example: catecholamine neurotransmitter release. https://www.thoughtco.com/what-is-exocytosis- Effects of transport on the distribution of substances Substance transfer is affected by: ◦ Selective permeability of the BM ◦ Functional transport mechanisms (e.g., are there enough carrier substances, ATP, is the channel not blocked, etc.) THEREFORE, THE DISTRIBUTION OF SUBSTANCES ON BOTH SIDES OF THE BM IS NOT IN EQUILIBRIUM:  Ions and most solutes are not in equilibrium, e.g., the amount of Na+ and K+ on both sides of the BM changes as a result of the Na+/K+ pump (chemical gradient)  The balance of WATER is determined by the amount of dissolved salts (osmolarity) on both sides of the membrane, because thanks to this, water passes through cell membranes conditionally freely (the mechanism of osmosis!)  There is also electrical imbalance (e.g., potential difference) between EC and IC environment (i.e., electrical gradient) Basic mechanisms of the body’s defensive systems and regulation EC fluid – blood, flowing through the body, gets in contact with all the tissues and unites the internal environment of the body. Therefore, by performing blood tests, we can determine the state of health of the body: 1) we can evaluate the normal body functions 2) we can evaluate the pathological processes (inflammation, blood parasites etc.) Health is a successful process of development, maintenance and adaptation of autonomic, somatic, sensory, psychic functions in order to find a state of balance between the internal processes of the organism and the external environment. It is realized by body’s defensive systems! 16  The body’s defensive systems are morphofunctional mechanisms that ensure the integrity of the organism and the ability to resist harmful environmental influences. With defensive systems, the body isolates itself from the surrounding environment, maintaining homeostasis. Animal defensive systems are directed against external as well as internal threats, including pathogenic bacteria, viruses, parasites, and cancer. There are 3 main defensive systems: 1. Barriers: a) External barrier– skin, mucous membrane b) Internal barrier – histo-hematic barrier, cell membranes 2. Immune system 3. Protective reflexes 1. a) External barriers (Skin) Skin functions: Mechanically protects the organism from the influence of the external environment Determines the distribution of substances between the organism and the environment Protects against the UV radiation Bactericidal function Participates in body thermoregulation Receptor function 1. a) External barriers (Mucous membranes) Functions of the mucous membranes: Mechanically protect cavities and channels connected to the external environment E.g., respiratory, gastrointestinal tract By producing mucus, neutralize some chemicals, toxins, and flash away foreign bodies The antibacterial function is realized with bactericides and immune substances 1. b) Internal barriers: Consist of: 1) Histo-hematic barrier – vascular wall 2) Cell membrane – separates IC and EC environment Functions: Regulate the movement of substances: blood/interstitial space Defence function: protect cells (toxins, metabolic end products) Separate the interstitial fluid from the cell cytoplasm, ensures the distribution of substances between cells 2. Immune system... Protects the body from cells and substances with genetically unfamiliar characteristics. Immunity can be active and passive. It is managed by: ◦ Primary lymphoid organs: red bone marrow, thymus ◦ Secondary lymphoid organs: lymph nodes, tonsils, spleen, Peyer’s patches and mucosa associated lymphoid tissue (MALT4) 4 The mucosa-associated lymphoid tissue (MALT), also called mucosa-associated lymphatic tissue, is a diffuse system of small concentrations of lymphoid tissue found in various submucosal membrane sites of the body, such as the gastrointestinal tract, oral passage, nasopharyngeal tract, thyroid, lung, salivary glands, eye, and skin. 17  Types of immunity Immune responses can be either innate or acquired. Internal immunity is traditionally divided into two separate but interdependent components: the ancient innate immune systems (which has many separate aspects) and the more recently evolved adaptive or acquired immune systems. The responses of these two systems differ in their timing and in the degree of selectivity of the defense mechanisms employed: https://www.studocu.com/en-gb/document/university-of-leicester/an-introduction-to- physiology/immunity-and-vaccination/12985838 http://biology4me.weebly.com/sc912l1452-immune-system.html 1. Acquired. Probably the most familiar components of this system are antibodies, which may take days or weeks to build up after your first exposure to a disease (or vaccine) 2. Innate immunity encompasses an animal’s immune responses that come into play rapidly (even immediately) on exposure to any threatening agent and that do not depend on prior exposure to that agent. These responses are “ready-to-go” mechanisms that defend against foreign or abnormal material of almost all type, including pathogens, chemical irritants, and tissue injury accompanying mechanical trauma and burns. Acquired immunity rely on learned immune responses selectively targeted against a particular foreign material following the first exposure. Since it requires learning, acquired immunity takes considerably more time to be mounted and takes on one specific foe at a time. https://www.google.com/url?sa=i&url=https%3A%2F%2Fs5ee8b77f7f9dee0d.jimcontent.com%2Fdownl oad%2Fversion%2F1671427868%2Fmodule%2F8137978962%2Fname%2FSB025%252011.%2520IMMU NITY.pdf&psig=AOvVaw2VILFooTAaWZipa2E0ZpNC&ust=1693250966172000&source=images&cd=vfe& opi=89978449&ved=2ahUKEwiho43Eyf2AAxV_EBAIHdgZDGoQr4kDegUIARCiAg The role of leukocytes in providing different types immunity Cellular immunity is provided by aggressive T lymphocytes (T killers), forming a wall around a foreign antigen (e.g., transplant) and isolating it Humoral immunity is ensured by B lymphocytes, because plasmablasts are formed from B lymphocytes with the help of T helper cells, which produce specific immunoglobulins. 18  Non-specific immunity is provided by monocytes – the largest leukocytes appearing in the place of inflammation later than other defense cells. There monocytes turn into active macrophages, which release active antibodies – monokines (lysozyme and interferon), which provide nonspecific immunity, and substances that affect the differentiation of T lymphocytes and plasma cells. 3. Protective reflexes Protective reflex is the body’s response to a harmful irritant that is realized through the CNS Harmful effects cause protective reflexes such as coughing, sneezing, tearing, eye blinking, breath holding, fear of predators, fire or water, etc. If it is acquired during life, then it is called conditioned protective reflex, but there are also inborn unconditioned protective reflexes. Mechanisms of regulation of physiological functions Thanks to regulatory mechanisms, the organism exists as a whole. They ensure the adaptation of the organism to the environment; the internal environment of the organism is maintained relatively constant (homeostasis of the internal environment). Two basic regulation mechanisms are distinguished: 1. Humoral 2. Neural Humoral regulation mechanism ✓ Phylogenetically the oldest regulatory mechanism. ✓ Biologically active substances5, which are produced in the body itself and which are brought to all tissues and organs with the fluids of the internal environment (blood, lymph, interstitial fluid), participate in humoral regulation. ✓ Is relatively slow and inaccurate. ✓ From the moment of irritation to the response is about 23 seconds. Types of humoral regulation Non-specific humoral regulation – participate metabolic end products (CO2, lactic acid etc.) and various ions. Hormonal humoral regulation – gland and tissue hormones take part in it ✓ Gland hormones are produced by endocrine glands and endocrine cells (mainly in the gastrointestinal tract) ✓ Tissue hormones are produced by various tissues (prostaglandins, kinins, histamine, serotonin etc.) Neural regulation mechanism ✓ It is more accurate ✓ Information is sent along the nerve fibers to the response group of tissues (local action) ✓ It is faster ✓ Information is transmitted very quickly. ✓ There are impulses that propagate at a speed of 120m/s. ✓ It’s basically a reflex ✓ Information is transmitted in the form of impulses along the whole reflex arc, therefore it is called a reflex regulation 5 biologically active substances (metabolites, hormones, ions) released by cells, organs, and tissues 19  Reflexes - the response of any organism to the irritation of the external and internal environment, which is implemented by the nervous system through the CNS. Or in other words a reflex is a fast response to a change in the body’s internal or external environment in an attempt to restore homeostasis. Reflexes can be somatic reflexes, which involve contraction of skeletal muscles, or autonomic reflexes, which regulate smooth muscle, cardiac muscle, and endocrine glands. Each reflex is based on a reflex arc, in which five components are conditionally distinguished: 1) Sensory receptor 2) Sensory (afferent) neuron 3) Interneuron in in the central nervous system 4) Motor (efferent) neuron 5) Effector (target organ) https://www.pearson.com/channels/anp/asset/3fda5b66/initiat 1. All reflex arcs begin with a sensory receptor. ing-stretch-reflexes Sensory receptors vary widely within the body but share a common function: they transduce a range of environmental energy, or the presence of an environmental chemical, into a cellular response that directly or indirectly produces action potentials along a sensory neuron. In other words, these receptors collect environmental signals and turn them into a format that can be understood by the nervous system. For example, receptors of the retina transduce light; those in the skin transduce heat, cold, pressure, and other cutaneous stimuli; muscle spindle receptors transduce stretch; and taste receptors transduce chemical stimuli from ingested material. Action potentials resulting from stimulus transduction are generated along sensory neurons at a frequency proportional to the intensity of the transduced stimulus. 2. The next component in a reflex arc, alluded to earlier, is a sensory neuron (CNS afferent). These neurons carry action potentials, resulting from receptor activation, to the CNS. Sensory neurons enter the spinal cord by way of the dorsal roots or enter the brain through cranial nerves. 3. The third component of a reflex arc is a synapse in the CNS. Actually, for most reflex arcs, more than one synapse occurs in series (polysynaptic). In polysynaptic reflexes, where one or more neurons lie between the sensory neuron input to the CNS and the motor neuron output, these interposed neurons are called interneurons and can be considered part of this third component of the reflex arc. 4. The fourth component is a motor neuron (CNS efferent), which carries action potentials from the CNS toward the synapse with the target (effector) organ. Motor neurons leave the spinal cord through the ventral roots, and motor neurons leave the brain through the cranial nerves. 5. The last component is some target organ (effector organ) that causes the reflex response. This is usually a muscle, such as the skeletal muscle fibers of the quadriceps muscle of the leg, in the case of the “knee jerk” (muscle stretch) reflex, or the smooth muscle of the iris in the pupillary light reflex. The target could also be a gland, such as a salivary gland in the salivary reflex. Reflex actions are rapid and happen without thinking e.g., you would pull your hand away from a hot flame without thinking about it. !!!Receptors A receptor is a protein molecule that receives chemical signals from outside a cell. Each receptor has a corresponding, adequate stimulus, which is a stimulus, to which the receptor is most sensitive (taste receptor – food molecule etc.). Receptors: ✓ Detect stimulus (detectable change) from different modalities (energy forms) e.g., light, heat, sound, pressure, chemical changes 20  ✓ Convert forms of energy into electrical signals (action potentials) Process is called transduction A molecule that binds to a receptor is called a ligand, and can be a protein or peptide (short protein), or another small molecule such as a neurotransmitter, hormone, pharmaceutical drug, toxin, or parts of the outside of a virus or microbe. Types of receptors: Photoreceptors o Responsive to visible wavelengths of light Mechanoreceptors o Sensitive to mechanical energy Thermoreceptors o Sensitive to heat and cold Osmoreceptors o Detect changes in concentration of solutes in body fluids and changes in osmotic activity Chemoreceptors o Sensitive to specific chemicals o Include receptors for smell and taste and receptors that detect O2 and CO2 concentrations in blood and chemical content of digestive tract Nociceptors o Pain receptors that are sensitive to tissue damage or distortion of tissue The simplest reflexes can be realized by the lower parts of the CNS (spinal cord), but the most complex reflexes that are very important to life are usually regulated by the higher parts of the CNS. It means, the more complex function that needs to be regulated, the higher part of the CNS does it. Classification of reflexes 1. Inborn reflexes or unconditioned reflexes These reflexes are further divided: a) Autonomic – related to the regulation of internal organs b) Somatic – related to the regulation of skeletal muscle functions 2. Learned (acquired) reflexes or conditioned reflexes The unconditioned reflex is the innate reaction of the organism, which is the same among the members of the given species. They are characterized by a permanent and clear connection between action on the receptor and a certain response, ensuring that organisms adapt to stable living conditions. A conditioned reflex is a reaction that the body acquires during its life and responds to the stimulation of receptor. Conditioned reflexes are developed through the formation of temporary connections in the cerebral cortex and serve as mechanisms for adaption to the complex changing environmental conditions. 21  Difference between unconditioned and conditioned reflexes Unconditioned reflexes Conditioned reflexes Innate adaptive responses, usually within Adaptive responses during life species Stable adaptation reactions, as they persist Labile because they last only as long as the throughout life, regardless of the frequency of conditions under which the reaction occurs use. exist. They are species specific reflexes because they A reflex usually has an individual nature, are characteristic of all individuals of the same acquired through the individual’s experience species They are realized through any part of the CNS They are realized only through the highest parts of the CNS Only strictly defined reflex arc Reflex arcs can be different, even combined Reflexes in classical concepts are controlled by the nervous system. In the modern sense, hormonal control can also be realized in a reflective way. An example of reflector hormonal regulation: Water deficit in the body ↑ Extracellular osmolality ↑ Antidiuretic hormone (ADH) secretion (neurohypophysis) ↑ ADH in blood plasma ↑ Water reabsorption in nephrons ↑ Water elimination ↓ Extracellular osmolality ↓ Summary of humoral and neural regulation Humoral regulation Neural regulation Phylogenetically older Relatively newer Slower (up to 0.5 m/s) Faster (up to 120m/s) Responses are diffuse, imprecise Responses are accurate Usually does not pass through the CNS Always realized through the CNS Information is transferred by hormones and Information is carried by impulses metabolic end products Information travels through blood vessels Information travels though neurons 22