1.1 G1 Functional Organization of the Human Body PDF

Hey, everyone. Welcome to Physiology and Pathophysiology. Uh, this is our first lecture together. Functional organization of the human body. Uh. Most of guidance text is concerned with how each organ or tissue contributes to homeostasis. Homeostasis is the maintenance of nearly constant conditions...

Hey, everyone. Welcome to Physiology and Pathophysiology. Uh, this is our first lecture together. Functional organization of the human body. Uh. Most of guidance text is concerned with how each organ or tissue contributes to homeostasis. Homeostasis is the maintenance of nearly constant conditions in the internal environment. Disease is often considered to be a state of disrupted homeostasis. Part of physiology seeks to explain how the various physiologic processes are altered in the disease and injury. This chapter is an overview of many topics. We'll cover more in depth later, such as the air concentration maintained by the transport ions we will discuss in chapter four. Extracellular. There are large amounts of sodium chloride and bicarbonate ions as well as nutrients for cell. Uh. This includes oxygen, glucose, fatty acids and amino acids. Intracellular large amounts of potassium, magnesium, and phosphate. Extracellular fluid is transported through the body in two stages. Stage one is movement of blood through the body and blood vessels. Stage two is movement from the capillaries to the intercellular space. As blood passes through the capillaries, exchange continuously occurs between the plasma and interstitial fluid. Few cells are located more than 50 micrometers away from a capillary. This ensures diffusion of almost any substance within a few seconds. Each time blood passes through the body, it flows through the lungs, picking up oxygen in the alveoli. You have the membrane, which is the membrane between the alveoli. And the aluminum of the pulmonary capillaries is only point 4 to 2 micrometer thick. A large portion of the blood passed through the walls of the gastrointestinal tract, picking up carbohydrates, fatty acids, and amino acids. Many substances absorbed from the GI tract are unusable, so the liver, along with fat cells, gastrointestinal mucosa, mucosa, kidneys, and endocrine glands change these substances into more usable forms. Of course, as you know, the liver also eliminates waste products and toxic substances. Of course, as you know, the lungs also remove CO2, which is the most abundant of all metabolic products. Kidneys remove most of the products not needed by the cells. They filter large quantities of plasma into the renal tubules, then reabsorb the needed substances. The liver has many functions, one of them being detoxification or removal by ingested drugs and chemicals excretes many of these into the bile to be eliminated by feces. GI tract uh, it eliminates undigested material and so some metabolic waste. The nervous system is composed of three parts. Sensory. Central. The central nervous system and motor output. Sensory receptors detect the state of the body and its surroundings. Brain stores its information and generates thoughts and then determines reactions that the body performs. Appropriate signals are then transmitted through the motor output portion of the nervous system. Organs and tissues that secrete chemical substance are called hormones. Hormones are transported in the extracellular fluid to help regulate cellular function. One example of hormones is insulin, which is secreted by the pancreas and controls glucose metabolism. The endocrine system will be covered thoroughly next semester. Immune system includes white blood cells. Tissue from white blood cells. The thymus. Lymph nodes, and lymph vessels. It provides a mechanism for the body that distinguish its own cells from foreign substances, and destroys invader cells by phagocytosis or antibodies. Intake system includes skin as well as hair, nails, and glands that cover cushion and protect deeper tissues and organs. It also system temperature regulation and waste excretion. Reproductive system helps maintain homeostasis by generating new beings. The human body has thousands of control systems throughout. Some of these include genetic control systems within the cell, within organs to control that organ, or throughout the body to control the interrelationship between organs. Examples are oxygen and CO2 regulation, as well as blood pressure. Most systems in the body are controlled by negative feedback mechanisms. When a factor is abnormal, a negative feedback is initiated, which through a change, returns the factor to normal. Example is elevated CO2 stimulates the restless center, causing the kidney. With a positive feedback, the initial stimulation causes more of the same. Um. It is sometimes known as a vicious cycle and can lead to instability rather than stability. One example of positive feedback that can be useful is the blood clotting cascade, or cervical stimulation causing uterine contractions. Uh, a baby's head stimulates the cervix, which causes contractions, which of course moves the baby and cause more stimulation to the cervix, creating a positive feedback loop. Uh, when someone loses two liters. Uh, negative feedback mechanism can cause a return to normal. Um, but after two liters, uh is lost. Positive feedback mechanisms can cause death unless there's intervention. Uh, the cell and its functions. Most cells, except for fat, are comprised of 70 to 85% water. Important ions in the cell are potassium, magnesium, phosphate, sulfate, bicarbonate, and small quantities of sodium chloride and calcium. The second most abundant substance is proteins, which is more like 10 to 20% of the cell. Structural proteins are mainly present as long filaments, commonly uh microtubules, which provide the cytoskeleton of the cellular organelles. Examples are cilia, nerve axons, meiotic spindles, and then filamentous tubules that hold the cytoplasm and nuclear plasm together. Functional proteins are mainly the enzymes of the cell, often mobile and in tubular, uh, globular form. They are the mainly the enzymes of the cell and are often, uh, mobile in the cellular fluid. Lipids are several different types of substances grouped together because of their ability to dissolve in organic solutions, as opposed to water. This is called hydrophobic or lipophilic, which is such an important topic. We'll be talking about it many semesters from now. Especially important are phospholipids and cholesterol, which constitute about 2% of the cell mass. Phospholipids are mainly insoluble in water and used to form the cell membrane and intercellular membrane barriers that separate cellular compartments. Carbohydrates are used for nutrition and structure. Most cells do not maintain large amounts, uh, around 1% in intracellular, although. It's always present as glucose in the surrounding extracellular fluid. Cell contains intracellular organelles which are highly organized physical structures critical for cellular function. For example, mitochondria, most organelles are covered by membranes composed of lipids and proteins. These lipids provide a barrier and impedes movement of water and water soluble substance uh, because water is not soluble in lipids. Proteins such as the integral proteins you see in the drawing often penetrate all the way through membranes, providing pathways for the passage of specific substances. The cell membrane envelops the cell in a thin, pliable, elastic structure. 7.5 to 10 nanometers thick. It is composed almost entirely of proteins and lipids. Cell membrane impedes penetration by water soluble substances. Each layer is only a molecule thick. Each phospholipid molecule has a hydrophilic end and hydrophobic phosphate. In this hydrogen silicate, the fatty acid is hydrophobic. The outside of this membrane is in contact with intracellular and extracellular fluid, while the inside is impenetrable by water soluble substances, hydrophilic substances can easily pass while it is impenetrable, impenetrable to hydrophobic substances. An anthropomorphic molecule. It's part hydrophobic, while another part is hydrophilic. This creates one of the essential functions of the plasma membrane. It's impenetrable to most water soluble molecules because it's insoluble to the inner oily core region, which is here. You can see on the right, uh, the glycerol and the fatty acid chains are nonpolar, meaning they are not water soluble. And whereas the head is polar. In the lipid bilayer, the head is facing outward in contact with water. Uh, two layers of these empathic molecules are arranged so that their lipophilic Tels are facing each other, and therefore not in contact with water. There are two types of cell membrane proteins integral proteins and peripheral proteins. Integral proteins protrude all the way through the membrane. Some provide structural channels or pores to which water molecules or water soluble substances can diffuse. Some act as carrier proteins for transport for transporting substances that otherwise cannot penetrate the membrane. Some act as active transport carriers, transporting substances opposite their electrochemical gradients, uh, while some serve as receptors. The specific ligand binds to the external portion, causing conformational changes, which activates the intracellular portion and thus relays extracellular information. Intracellular. You'll learn this in minute detail in pharmacology. A ligand is a hormone or a drug. Uh proteins attach only to one surface of the membrane and do not penetrate all the way through. They function almost entirely as enzymes or as controllers of transport of substances through pores. Carbohydrates occur in combination with proteins and lipids, forming glycoproteins and glycol lipids. In fact, most of the integral proteins are glycoproteins. The glass saw portions protrude to the outside of the cell, dangling outward from the cell surface. Probably glycans, which are mainly carbohydrates, are loosely attached to the outer cell surface as well. That's the entire outside surface of the cell. Often as a loose carbohydrate coat, the cell glycol calyx has many functions. Many have a negative electrostatic charge, giving the cell surface an overall negative charge. Think like okay, lots of other cells can attach to each other, thus attaching cells together, and many act as receptors for bonding hormones. Some carbohydrate moieties are part of immune reactions, as we will discuss later. The endoplasmic reticulum is a network of tubular structure called systole and flattened circular structures in the cytoplasm. It helps process molecules by the cell and transports them. Their specific destinations inside or outside the cell walls are made out of a bilayer and total surface area between 30 to 40 times the cell membrane space inside, the air is connected with the space between the two membrane surfaces of the nuclear membrane. The surfaces and multiple enzyme systems attached provide the mechanism for many of the cell's metabolic functions. The rough or granular endoplasmic reticulum has ribosomes composed of RNA and proteins, a function to synthesize new protein molecules in the cell. This is where DNA translation occurs, something we will discuss later. Smooth or granular endoplasmic reticulum synthesizes lipid substances and other processes promoted by interactive ocular enzymes. The Golgi apparatus is closely related to the endoplasmic reticulum. It has a membrane similar to smooth ER. It is prominent in secondary cells, where it is located on the side of the cell from which the substances are extruded. Golgi functions closely with the ER. Small transport vesicles continually pinch off from the air and fuse with the Golgi. Transported substances are then used to form lysosomes, secondary vessels, and other cytoplasmic components. Almost all substances formed by the cells are created by the ER Golgi apparatus and then released by secretary vessels or granules. Lysosomes are organelles that form by breaking off the Golgi apparatus. They then dispersed throughout the cytoplasm. They allow the cell to digest, uh, damaged cellular structures, food particles ingested by the cell, and unwanted matter such as bacteria. In order to do that, they're filled with 40 different hydrolase enzymes. These enzymes break down substances, such as proteins that are hydrolyzed to form amino acids. They are surrounded by the typical lipid bilayer, which prevents the enclosure, the enclosed hydrophilic enzymes from coming into contact with other substances in the cells. However, if conditions occur that cause a break in that bilayer, uh, they will digest those enzymes, will digest anything they come in contact with. Baroque systems are similar to lysosomes, except they're self-replicating. They contain oxidizers rather than high places. They utilize hydrogen peroxide to oxidize many substances, including long chain fatty acids. One example is alcohol converted to a fuel aldehyde, uh, by paroxysms in the liver. Mitochondria are present in all areas of the cell cytoplasm. The total number varies based on the energy requirements. They are more concentrated where energy is needed and there self-replicating whenever synergy is needed as well. They're composed mainly of two lipid bilayer membranes and outer and inner inner membrane. Many inner folding of the inner membrane form crispy where oxidative enzymes are attached. The info influence provide a large surface area for chemical reactions to occur. The enzymes on the crust cause the oxidation of nutrients from carbon dioxide and water, and releasing energy, which is utilized to synthesize acid triphosphate or ATP. The ATP then diffuses through the cell to be utilized wherever it is needed. Up to 95% of the cell's energy is formed, not in the mitochondria. A cell cytoskeleton is a network of fibular proteins organized into filaments at tubules. They begin as precursor proteins synthesized by ribosomes in the cytoplasm. The precursor molecules are then polymerized before macro filaments that occurred ectoplasm to form elastic support for the cell membrane. These are the basis for contraction of muscles and will be discussed more later. Intermediate filaments are strong, rope like filaments that work with microtubules to provide strength and support. They are found in all cells. Functions are mainly mechanical and less dynamic than actin. All cells have intermediate filaments, although their structures vary depending on the cell type. A major function of microtubules is they act as a cytoskeleton, providing rigid physical structures for certain parts of the cell. The cytoskeleton determines self shape and allows cells to move. The nucleus is the control center of the cell. It sends messages to the cell to grow, mature, replicate, or die. The nucleus contains the cell's DNA, which determines the characteristics of cell proteins. The nuclear membrane is also called. The nuclear envelope is actually two separate bilayer membranes. The outer membrane is continuous with the air. It has several thousand nuclear pores, which allows molecules to pass easily. The nucleus, uh, does not have a limiting membrane. It is simply an accumulation of large amounts of RNA and proteins. It largest considerably when the cell's actively synthesizing proteins. To live and grow, a cell must obtain nutrients and other substances from surrounding fluids. Most substances pass through the cell membrane by the process of diffusion or active transport. Substances move through cell membrane pores or, if they are lipid soluble and diffuse through the cell membrane. Diffusion is a simple movement through the membrane caused by entropy for the disorder of a system. That is, it's the random motion of molecules. Active transport involves carrying a substance through the membrane by a protein structure that penetrates through the membrane. We'll go over transport mechanisms extensively in chapter four. Large particles enter the cell by a specialized function of the cell membrane called in those. There are two forms penal site substance and phagocytosis. You know, psychosis is the ingestion of small or minded particles that form vessels inside the cell cytoplasm. You know, psychosis is the only way large macromolecules such as protein can enter the cells. Cell typically has receptors on the surface membrane that the molecule attaches to, stimulating imagination and the formation of a psychotic vessel. Of course, this movement requires ATP, because I ptosis occurs the same way as peanut psychosis, except it involves larger particles. Only certain cells have the capability of phagocytosis, especially defense mechanisms such as tissue macrophages and white blood cells. Because psychosis is typically initiated when a particles such as a bacteria, dead cell, or tissue debris combines with a receptor on a phagocyte. As we will learn later, in the case of bacteria, an antibody is already attached to the bacterium and that is what stimulates the receptors on the phagocytes. Almost immediately after a vessel appears inside cell, one or more lysosome attaches and empties its acid hydrolysis inside the vessel. Thus, a digestive vessels form the hydrolyzed of proteins, carbohydrates, lipids, and other substances begins inside the digested vessel. The products are substances such as amino acids or glucose, that can diffuse through the membrane of the vessel and into the cytoplasm. The residual body is what is left after digestion and is excreted through the cell membrane by exocytosis. Tissues of the body often decreased to a smaller size, such as after pregnancy or the mammary glands after lactation, or more appropriate to the current situation. Muscle atrophy from anesthesia. School and decreased gym activity. Lysosomes are responsible for much of this progression. Lysosomes also remove damaged cells or damaged portions of cells after cells damaged by any factors such as He, cold or trauma. Lysosomes rupture, releasing their hydrolysis, which begin digesting the surrounding organic tissue. If the damage is severe, the entire cell is digested, uh, which is called by the lysis. Lysosomes also contain bacterial agents that can kill phagocytes, bacteria before they could cause cell damage. Lysosomes play a key role in the process of autophagy, which is the housekeeping process meaning to eat oneself. Autophagy allows obsolete organelles and large protein aggregates. To be degraded and recycled. One example is liver mitochondria. Lifespan is ten days, for it is recycled. The endoplasmic reticulum is formed. By lipid bilayer. Similar to the cell membrane, walls are loaded with protein enzymes that catalyze the synthesis of many substances needed by the cell. Synthesis begins in the endoplasmic reticulum and products are passed to the Golgi apparatus. As we will discuss extensively later, proteins are synthesized within the ribosomes of rough ER. Lipids, especially phospholipids and cholesterol, are synthesized by the smooth ER incorporated into the lipid bilayer and cause it to grow. A smooth endoplasmic reticulum also provides enzymes that control glycogen breakdown when it is needed for energy. It also provide enzymes to detoxify substances such as drugs that could damage the cell. The Golgi apparatus provides additional processing of substances already formed in the air, but at the same time also synthesizing carbohydrates. They cannot be formed in the air, especially hyaluronic acid and conjugated sulfate. Substances are formed in the air, they are transported through tubules, the portions that lie near to Golgi, which you can see in this image. Transport vesicles containing synthesized proteins and other products, uh, are composed of smooth air, breakaway and diffuse the Golgi. The transport vesicles instantly fuse with the Golgi and empty its contents. As the secretions pass to the outermost areas of the Golgi, concentrating vessels formed by the Golgi breakaway and are secreted by the cell. This exercise of exocytosis replenishes the cell wall. To give an idea of the timeframe of this process. When the cell is bathed in amino acids, which you remember, weak amino acids are the building blocks of proteins. Uh, and in the ribosomes they are converted into the proteins of the roughly are protein molecules appear within 3 to 5 minutes. Within 20 minutes, newly formed proteins are in the Golgi, and within 1 or 2 hours, the proteins are secreted from the surface of the cell. In the body. Essentially, all carbohydrates are converted into glucose by the digestive tract, and liver proteins are converted into amino acids, and fats are converted into fatty acids prior to each other. Cells of the body. What's inside the cell? Glucose, fatty acids, and amino acids react with oxygen and release energy. Almost all of these oxidative reactions occur inside the mitochondria. The mitochondria makes ATP, which then is used throughout the body for subsequent metabolic reactions. ATP is composed of any ribose and three phosphate radicals. The last two phosphate radicals are connected by high energy phosphate bonds, shown here, uh, with the squiggly line. Uh, each of these bonds contains about 12,000 calories of energy per mole of ATP. This bond is also easily broken, so it can be utilized instantly when the energy is utilized. ATP is converted to ATP once ATP is formed. Cellular energy is utilized to form new ATP and the process starts over. ATP is called the energy currency present in the cell. It can be spent and reformed continually. It is also essential to note that the driver of the utilization of cellular nutrients is the formation of ATP, and the accumulation of ATP needing to be converted back to ATP. As we said before, 95%. Of the cells. ATP formation occurs in the mitochondria. The other 5% is formed by glycolysis. Glycolysis is the conversion of glucose in the pyruvate acid in the cell cytoplasm, the pyruvate acid that enters the mitochondria and is converted in acetyl-CoA inside a critical aid and enters the Krebs cycle, which splits it into hydrogen and carbon dioxide, which then diffuses out of the carbon dioxide in the fuse out of the cell and is excreted about the lungs, while the hydrogen combines with oxygen, which creates a tremendous amount of energy and is utilized to convert the ATP to ATP. The citric acid cycle is covered more thoroughly in chapter 68. ATP is used primarily for three major functions. The transport of substances through cell membranes and surfaces of chemical compounds throughout the cell. Lastly, mechanical work. Much of the energy of transport of ions is utilized to power a sodium potassium pump, which we will cover extensively later. Two types of movement of the cell are. Amoeba in motion. Cilia movement. Uh, Laban movement is a crawling like movement of an entire cell in relation to its surroundings. It begins with a protrusion of a podium from one end of the cell. A sort of podium projects away from the cell body and secures itself to a new area. Uh, and then the remainder of the cell is pulled towards it. B-Boy motion results from the continual formation of new cell membrane at the leading edge, reabsorption at the rear. Also essential are the attachment of a suit of podium to surround the tissue caused by receptor proteins inside the exo psychotic vesicles at the other end of the cell, the receptors pull away from their ligands and form in those mitotic vessels. In the image above, the cell is moving from the left to the right. Endocytosis occurs at the end, opposite of movement. These then move intracellular and are combined with the leading edge, where they add to the membrane and provide the receptors for attachment. Certain substances cause this amyloid locomotion. These substances are called chemotaxis substances and are the initiation of movement. It's called chemotaxis. We'll go over this more in detail next semester. ATP is required for all of this action. There are two types of cilia motile and non-motor. Both are motile. Cilia undergo quick like movement of the cell surface. Cilia moves forward with a sudden rapid whip like stroke 10 to 20 times per second. Then it moves back slowly, uh, towards its initial position. Rapid thrusting, whip like movement pushes fluid while the slow movement back has almost no effect. This movement occurs mainly in two main places in the human body the rest of the airways and inside the fallopian tubes. In the rest of airways, this cause mucus to move at about one centimeter a minute towards the fact that it continually clears the rest. Free passages of the particles that have become trapped in the mucus. We will cover the transport of the ovum in the fallopian tubes in the reproductive chapter next semester. Sperm for the gel movement is similar, but it occurs in quasi sinusoidal waves instead of whip like movement. Non motile primary cilia function as cellular sensory antenna. For example, they are found in kidneys in the epithelial cells of the tubules acting as flow sensors. Fluid movement causes the cilia for dead, causing changes in intracellular calcium signaling. Defects in the signaling are thought to contribute to various disorders, including polycystic kidney disease. In this lecture, we're going to talk about fluids and electrolytes as Module one, lecture three Guyton Chapter 25 and McCain's Chapter three. Fluid intake in output are balanced and we're just going to go through a few of those key concepts, daily intake of water. Twenty one hundred million a day. Normally you gain water from synthesising of oxygen and by the oxidation of carbohydrates, 200 milligrams a day. The daily loss of water and sensible water loss. Continuous water loss by evaporation from the rest of the track. And diffusion through the skin. This is independent of sweating three to four hundred million a day for the rest. Courtright fluid loss in sweat 100 milliliters today. Normally, of course, with activity that can increase greatly of the two leaders an hour and heavy exercise, water loss and feces and water loss by the kidneys. Kidneys is the most important means by which we're able to maintain body. Homeostasis can be as little as half a litre today a day and as high as 20 liters a day. So the body fluid compartments, we have the extracellular in intracellular compartments, exercisers, 20 percent of body weight, or about 14 liters, that's divided amongst the interstitial fluid, blood plasma, intracellular fluid, which will briefly look at some of those spaces. The intracellular fluid comprises 28 42 leaders, or about 40 percent of total body weight than the average person. You can see this diagram that I'm sure we've all seen before. So we're going to discuss the differences between the extracellular and intracellular fluid. Ionic composition of plasma and interstitial fluid is very similar. The most important difference is plasma contains a higher concentration of protein because the caterpillars have a very low permeability to plasma proteins. The distribution of fluid between intracellular extracellular compartment is determined mainly by osmotic effects of smaller sounds. We discussed that previously with large salads and small salads and relative energy. Cell membranes are relatively impermeable to most solids, but highly permeable to water. 80 percent of the total osmolarity of interstitial fluid and plasma is due to sodium chloride. Very important concept 50 percent of intracellular osmolarity is due to potassium. High osmotic pressure can develop across the cell membrane with small changes in concentration of sounds. Small changes can cause large changes in cell volume. In the chart over here on the left is important to learn to be able to understand these differences. Fluid Tomassi tenacity refers to whether a solution will cause a change in cell volume depends on the concentration of impermeable solids. These are important concepts, so isotonic neither shrinks nor swells or so. Normal sailing is isotonic, hypertonic water will diffuse into the cell, causing it to swell anything less than point nine percent sailing, sodium chloride, hypertonic water will flow out of the cell, causing it to shrink. Sodium chloride will be any concentration greater than point nine percent. Now, water movement across the cell membrane is so rapid that Osmolarity differences are usually corrected within seconds or at most minutes, although this does not mean the whole body equilibrium is reached that quickly. Water must be absorbed through the gut and transport of different tissues before equilibrium can be attained around 30 minutes after drinking water. The effects of that saline solution to the extracellular fluid, so this is something we do as practitioners all the time, where we're giving fluids, keep these two principles in line. Water moves rapidly across the cell membranes. Cell membranes are almost completely impermeable to many solids isotonic, sailing when added to extracellular fluid. The main effect is increased in extracellular fluid volume. So it doesn't cause fluid shifts, it doesn't cause shrinking or swelling in the cell. Hypertonic solution. When added to the extracellular fluid extracellular osmolarity is increased, causing osmosis of water out of the cells. Which increases the extra cellular volume causing the cell to shrink hypertonic solution is added to extracellular fluid accessory, extracellular osmolarity decreases and causes osmosis of water into the cells, causing the cells to swell. Both intracellular and extracellular volumes are increased, although intracellular is increased to a greater extent. And this chart depicts that what we were just talking about and I will discuss some clinical abnormalities. We'll start with hyponatremia. Sodium chloride accounts for more than 90 percent of the extracellular fluid salt, so hyponatremia can result from a loss of sodium or addition of excess water. So you're diluting or you're losing the sodium. A rapid reduction of plasma sodium concentration can coswell cell swelling, which can cause brain cell edema and neurologic symptoms. Hyponatremia evolves slowly. When hyponatremia evolves slowly, tissues respond by transporting ions into the extracellular compartment, preventing swelling, but leaves the cells vulnerable to rapid correction. Hypernatremia can be caused by a loss of water or excess sodium in the extracellular fluid. Simple dehydration is the most common cause can also be caused by excessive addition of sodium chloride to the extracellular fluid. So if we had hypertonic sailing infused, it causes the loss of intracellular water and so shrinking. Pulls water out of the cells and here's a summary chart of hyper and hypernatremia Eyadema Intercellular Dema can be caused by hypernatremia depression or the metabolic system of the tissues, lack of adequate nutrition to the cells, inflammation causing increased permeability and solids to the fusing into the cells causing inflammation are causing edema, depress the pressure of the metabolic system of the tissues, and lack of adequate nutrition of cells can lead to decreased cellular function, decrease eye on transport leading to edema, extracellular edema, abnormal leakage of fluid from the plasma to the interstitial space across the capillaries. Or it can be caused by a failure of the lymphatics to return fluid from the interstitial back to the blood. There's a summary of causes on page 316 and 317 indicating that you should look at other causes of edema. Heart failure. The heart fails to pump blood, normally causing increased capillary pressures and increased capillary filtration. Decrease your blood pressure at the same time, leads to increased retention of salt and water by the kidneys lead to hypertension. This edema that's caused by decreased kidney excretion of salt water, sodium chloride mostly remains in the extracellular compartment, so causes widespread increases in interstitial fluid volume hypertension. Because of the increased blood volume, edema can be caused by decreased plasma proteins, causes of plasma colloid, narcotic pressure, osmotic pressure to fall, leading to increased capillary filtration, extracellular edema. Their safety factors that normally prevent edema, low compliance of the interstitial, the ability of flow to increase 10 to 50 fold and the down of interstitial fluid protein concentration. Fluids in potential spaces of the body, so there are many potential spaces of the body. Some of those are plural. Pericardial, peritoneal and synovial cavities, these foods are viscous, tenacious fluids that lubricates the surfaces, lymphatic vessels are connected to all of these directly or indirectly, and they drain protein from these potential spaces. And an effusion is when edema occurs and the sucking subcutaneous tissues adjacent to the potential space. And in the abdominal cavity that's called anaesthetise, something we're probably all familiar with. Hey everyone. This is membrane potentials and action potentials. A concentration difference of ions across a selectively permeable membrane can create a membrane potential. The potassium concentration is great inside a nerve fiber, but very low outside because of this large concentration gradients. Uh, there's a strong tendency for potassium ions to diffuse outward, uh, and as they carry their positive electric charge to the outside as well. This creates a positive charge on the outside of the membrane and a negative charge on the inside of the membrane. Uh, very quickly, within about one millisecond, the electrical difference between the inside and outside becomes great enough to block further potassium diffusion to the exterior. Despite the high ion concentration gradient, this potential difference is about -94 millivolts. Sodium ions have a charge and a high concentration outside and a low concentration inside, allowing the same phenomena. Positively charged sodium ions diffuse intracellular, creating negative outside and positive inside. Again, this membrane potential rises enough to stop further diffusion within milliseconds. Uh, and this is positive 61 millivolts. As you can see, the. Electrical potential or diffusion potential of a particular ion through the membrane is called the nurse potential. The magnitude of the nurse potential is determined by the ratio of concentrations of that specific ion on the two sides of the membrane. Greater concentration differences, and therefore tendency to diffuse, means the greater the electrical charge required to stop its diffusion. The electromotive force can be calculated by using the Nernst equation written here. You can see it is the logarithmic function of the concentration inside of any specific ion in the body over the concentration outside. The golden equation can be used to calculate the diffusion potential when there are several different ions. Uh, and I will go over the Goldman equation. Uh, it is used to calculate the diffusion penitential when the membrane is permeable to several different ions. As I said, it is based on three factors. The popularity of the electrical charge of each ion, ability of the membrane to each ion, and the concentration of the respective ions on the outside and inside of the membrane. Goldman equation makes four key points evident. Sodium. Potassium chloride ions are the most important ions involved in the development of the membrane potential and nerve muscle fiber and neuronal cells. The concentration gradient of each of these ions helps determine the voltage of the membrane potential. The quantitative importance of each of these ions is proportional to the membrane permeability for that particular ion. The positive ion concentration gradient from the inside the outside causes electrode negativity. Um, and the permeable permeability of sodium and potassium channels undergoes rapid changes during nerve impulses, whereas the probability of chloride ions does not change greatly. This is the primary responsibility for signaling transmissions in neurons. In cardiac pacemaker cells, the membrane potential is continuously changing as a cell is never resting. In many other cells there is a resting period. Uh, this period is when the membrane potential can be measured. Membrane potential changes in response to various stimuli which alter activities for various ion transporters. Measuring membrane potential is simple in theory, but difficult in practice. An oscilloscope is utilized to record rapid changes in membrane potential transitions of nerve impulses. The resting membrane potential of large nerve fibers is about -70 millivolts. Remember, the sodium potassium pump is an electric genic pump because three sodium ions are pumped to the outside for each two potassium ions inside, but at the same time, this creates a large concentration gradient for sodium and potassium across the membrane. Gas leaks even in a resting cell. Sodium ions may also leak of the channel is 1000 times more permeable to potassium. This difference in permeability is the key factor in determining the level of the normal resting membrane potential. The important factors for establishing the normal resting membrane potential are the potassium diffusion potential of sodium diffusion potential, and the contribution of the sodium potassium pump. With potassium, there's a high ratio of potassium ions inside the cell, so there's a diffusion gradient to the exterior. This creates a nerve potential of -94 millivolts. Contribution of sodium is caused by the minute diffusion of sodium ions through sodium potassium channels. This creates a potential of positive 61 millivolts utilizing the Goldman equation, but considering only sodium, potassium, and potassium, this gives a potential of -86 millivolts. The sodium potassium pump moves three sodium ions outside and two potassium ions inside, resulting in negative four millivolts. Summary is almost all the resting membrane potential is determined by potassium diffusion, along with everything taking into account the net membrane potential is about -90 notebook's. Nerve signals are transmitted by action potentials, which are rapid changes in the membrane potential that spread rapidly along the nerve fiber membrane. They begin with a sudden change from the lower resting membrane potential to positive, and ends almost as rapidly back to negative. The action potential moves along the nerve fiber until it comes to the fibers end. There are three stages of the action potential the resting stage when the membrane is said to be polarized because of the -70 millivolt membrane potential, the depolarization stage, the membrane suddenly becomes permeable to sodium ions, allowing the rapid diffusion of the positively charged sort of ions to the interior of the axon. The repolarization stage is when, within a few ten hundredths of a second, the sodium channel begins to close and the potassium channels open to a greater degree than normal. The re polarisation process takes over and the membrane and the membrane potential returns to normal. The action of the voltage gated sodium channels is necessary for both depolarization and the repolarization of a nerve. There are two gates of the voltage gated sodium channels the activation gate, which is near the outside, inactivation gate, which is near the inside for activation of the sodium channel. When the membrane potential becomes less negative, rising from -74 to 0, it reaches a voltage which is usually around -55. It causes a sudden change in the activation gate, flipping it all the way open, and activation occurs in the same increase in voltage that open the activation gate. Gate closes the inactivation gate. Kourtney. Though the inactivation gate is closed a few ten hundredths of a second after the activation gate opens. This allows sodium to flow for a few ten hundredths of a second. The activation gate will not reopen until the membrane potential returns towards the resting membrane state. During the resting state, the gate of the potassium channel is closed, preventing calcium ions passing through the exterior. When the membrane potential rises towards zero, the gates open, allowing potassium diffusion. There's a slight delay in opening this channel, and because of this delay, about the same time the potassium channel opens is when the sodium channels are closing. Sodium stopped entering the cell at the same time, uh, potassium exits the cell, leading to repolarization and for recovery of the resting membrane potential. Being the resting state that conducted for potassium ions is 50 to 100 times. Greater than the conductance for sodium ions. At the onset of action, potential sodium channels almost instantaneously become activated and allow 5000 fold increase in sodium conductance, the inactivation process that closes the sodium channels within another fraction of a millisecond, uh. During the early portion of the activation potential, far more sodium channels flow. Far more sodium ions flow to the interior than potassium ions to the exterior, causing the membrane potential to become positive. Sodium channels then closed and the potassium channels open, allowing for rapid loss of potassium to the exterior, but no flow of sodium to the interior. Consequently, the action potential quickly returns to its baseline. Positive feedback cycle opens the sodium channels. Uh, if any of that causes enough initial rise in the membrane potential from a -70 towards zero, the rising voltage will cause many voltage gated sodium channels to open. The rapid sodium inflow causes more voltage gated channels to open, which causes more sodium, the inflow which causes more channels to open, and so on and so on, etc., etc. this positive feedback cycle continues until all voltage gated sodium channels are activated. In order to cause this, sudden rise in the membrane potential of 15 to 30,000,000V is usually required in a large nerve fiber, a change from -70 up to -55 millivolts usually causes the positive feedback loop to begin. And action potential elicited at any point in excitable membrane excites adjacent portion of portions, resulting in propagation along the membrane. A nerve or muscle impulse is a spreading of an action potential. There's no single direction of propagation. The action potential travels in all directions away from the stimulus. This is an all or nothing principle. Uh, that means once an action potential has been elicited at any point on the membrane. The depolarization process travels over the entire membrane if conditions are right. But if it's not right, the travel does not occur at all. Tigré shows a normal nerve fiber. Figure B shows a nerve fiber that has been excited in its midpoint, uh, which suddenly develops increased possibility for sodium. The arrow shows local circuit of current flow from the depolarized area to the membrane to the adjacent resting membrane areas. These positive charges increase the voltage for a distance of 1 to 3mm inside the large myelin, uh, fiber. Therefore, the sodium channels in these areas open immediately. An explosion. Explosive action potential spreads. Transmission of each action potential along a nerve fiber. Slightly reduces the concentration differences of sodium. Potassium inside and outside the membrane. For a single action potential, this effect is so my note cannot be measured. It takes 100,000 to fight to 50 million impulses, uh, before an action potential would cease re-establishment of the concentration gradient. It's through the sodium potassium pump. Uh, just as it is. As we previously described, the sodium potassium pump increases its activity when excessive sodium ions accumulate inside the brain. Repetitive. Self-induced discharge, of course, occurs normally in the heart, most smooth muscle and neurons of the central nervous system. Uh, these are the three examples. For spontaneous fitness to occur, that membranes must be permeable enough to sodium ions to allow automatic membrane depolarization. The rhythmic control center of the heart. -62. -70 millivolts is the resting potential, which is not enough negative voltage to keep the sodium and calcium channels all completely closed. Since some sodium calcium channels are open and air flow inwardly, and a positive feedback cycle began at the end of each action central for a short period uh. Thereafter, the membrane becomes more permeable to potassium ions, increasing the outflow of potassium, uh, and increasing the negative charge. Uh, leading this is hyper polarization, uh, this greater negativity. Lasts longer and takes longer to depolarize, creating the rhythmic. In order to continue further, we have to learn about some special characteristics of nerves, uh, and have to know some basic terminology for cells. Make up the myelin sheath that is deposited around the axon of a million nerve fibers. They contain single myelin, which is the substance contained in Schwann cell membranes. That is an excellent electrical insulator. Uh, decreases ion flow of 5000 fold. A node of Ranvier is the area of 2 to 3 micrometers that link between successive Schwann cells for ions can flow with these, almost no ions can flow through the thick myelin sheath. It is important to nerve to note that nerve potential velocity varies from as little as 0.25 milliseconds in a small on my lay fiber to as much as 100m of second in myelinated fibers. Solitary conduction is when electrical current flows through the surrounding extracellular fluid outside the myelin sheath, as well as through the axon plasm inside the axon from node to node. This causes depolarization to jump. Along intervals along the axis of the nerve fiber, which increases the velocity of nerve transmission as much as 50 fold and conserves energy for the axon because only the nodes depolarize. Any factor that causes sodium ions to to begin to diffuse inward through the membrane is often insufficient. Numbers can begin the positive feedback loop. This can result from mechanical disturbances of the membrane or chemical effects on the membrane, as well as passage of electricity through the membrane. This is the micro circulation and the lymphatic system. The micro circulation of each organ is organized to serve that organ specific needs. Each artery entering an organ branches 6 to 8 times, and then that artery becomes small enough to be called arterials because they have a general internal diameter of 10 to 15 micrometers. The arterials branch 2 to 5 more times through a diameter of 5 to 9 micrometers, at which point they become capillaries. The arterials are highly muscular, while the arterials only have a smooth muscle fibers encircling the vessel at intermittent points. And you can see that in this picture, there's a pre-calculated sphincter at the point where a material turns into a capillary. This sphincter can open and close the entrance to the capillary. The internal diameter of the capillary is 4 to 9 micrometers, which is fairly large enough for red blood cells to squeeze through. The thickness of the capillary is only 0.5 micrometers, which allows for rapid diffusion. The capillary membrane contains pores called intracellular clefts, which are thin, slated curving channels that lie between the endothelial cells. Fluid can pass freely through this cleft, and there's also. There also normally uniform spacing of around 6 to 7 nanometres. The thermal motion of water and water soluble ions is so rapid that they are able to diffuse with ease through these pores, or is in the capillaries of some organs have special characteristics. Uh, in the brain there are tight junctions that allow only extremely small molecules such as water, O2, and CO2 to pass in the liver. The intercellular clefts are really wide open in the GI tract, plus sized are midway between those of muscle and liver cells. The vessels for the kidney. There are finished rations that allow tremendous amount of small molecule. And ionic substances to pass. Blood does not usually flow continuously through the capillaries. Instead, it turns on and off every few seconds or minutes. Uh, this is caused by vessel motion, vessel motion, or the intermittent contraction of the arterials and pre- calculated sphincters. The most important factor affecting the opening and closing of the materials, and thus the regulation of vessel motion, is the concentration of oxygen in the tissues. When oxygen concentration decreases, closing occurs less and. And the opening last longer. Diffusion through the capillary membrane is the most important means of transferring substances between plasma and interstitial fluid. Lipid. Solid soluble molecules diffuse directly through the cell membrane. This includes oxygen and carbon dioxide. Water soluble substances cannot pass through the membrane, so they must pass through the class. Water can diffuse through the capillary membrane at a rate of about 80 times greater than that, then the rate of capillary blood flow. Although the capillaries in various tissues have extreme differences in their permeability, the diffusion rate is affected by the molecular weight of the substance, as well as the concentration difference between the two sides of the membrane. About one sixth of the total volume of the body consists of the spaces between cells called the interstitial. The fluid that fills these spaces is called interstitial fluid. This space contains collagen, fiber bundles and pretty glycan filaments, creating a tissue gel. This makes it difficult for the water to flow around. When fluid is not contained in this shell, it can flow freely. This is usually less than 1%, although when edema develops, this can expand tremendously. Hydrostatic and colloid osmotic forces determine fluid movement throughout the capillary membrane. There are four primary forces that determine fluid movement into and out of the interstitial fluid or the capillary. Uh. This is capillary pressure. Interstitial fluid pressure. The plasma colloid osmotic pressure. In the interstitial fluid. Colloid osmotic pressure. These forces are called starling forces. Capillary hydrostatic pressure averages 17mm of mercury and tends to force fluid outward through the capillary membrane. The interstitial fluid hydrostatic pressure averages negative three, although it is different for different values in different tissues. The plasma colloid osmotic pressure averages 28 and the interstitial fluid colloid osmotic pressure averages eight. The net filtration pressure is calculated with the formula here uh above the vessel. Uh. If the net operation filtration pressure is positive, there'll be fluid for friction across the capillaries. If it is negative, they'll be fluid reabsorption into the capillaries. Under normal conditions, it's slightly positive. The amount of fluid filtered outward from the arterial end of the capillaries almost exactly equals the fluid returned to the circulation by absorption at the venous end. The average capillary pressure at the artery ends of the capillary is 15 to 25mm of mercury greater than Venus's. Because of this, fluid filters are the calories at the arterial ends but is reabsorbed back. Uh, definitions. Except. The lymphatic system represents an accessory route through which fluid can flow from the interstitial spaces into the blood. Almost all tissues of the body have special channels that drain excess fluid directly from the interstitial spaces. Most of the blood entering the interstitium is reabsorbed back into the capillaries at the venous air about, but about one tenth of the fluid instead enters the lymphatic capillaries and returns to the lymphatic system. This is approximately 2 to 3l a day. Length is derived from interstitial fluid flowing into the lymphatics. It is one of the major routes for reabsorption of nutrients from the GI tract, especially fats from food. About 120ml an hour flows in the average human. Any factor that increases interstitial fluid pressure also increases left flow. Pumping of the lymphatics is caused by external compression causing the negative interstitial fluid pressure. Okay. This is the regulation of bodily fluid compartments. Uh. There's a continuous exchange of fluid and solids with the external environment. Although bodily fluids remain remarkably constant, daily intake of water is around 20 100ml a day, 200ml a day are synthesized in sensible water. Loss occurs by evaporation for the rest of the track and diffusion through skin independent of sweating. What amounts to around 700ml a day of water loss, 3 to 400 of that is lost to skin, or another 3 to 400 is lost to the respiratory tract. The amount of water loss of sweat is highly variable, dependent upon physical activity in the environment. This can range anywhere from 100 million a day up to two liters an hour. Lastly, water loss occurs in the urine. Kidneys are the most important means by which the body maintains balance between water intake and output. Urine volume can be as low as half a liter a day to as high as 20l today. The total body fluid is distributed mainly mainly between two compartments the extracellular and intracellular compartments. 28 to 42l of fluid in the body are inside the cells, which are collectively called the intracellular fluid. The fluid of each of these cells has an individual mixture of constituents, but concentrations are overall similar to each other, which is why it's considered one large fluid compartment outside the cell, or the extracellular compartment is about 14 layers, and this is made up of interstitial fluid and plasma. Intracellular and extracellular fluids are separated by a cell membrane that is highly permeable, uh, to water, but not permeable to most electrolytes in the body. Uh intracellular fluid contains only small quantities of sodium and chloride and almost no calcium, but it contains large amounts of potassium and phosphate. The distribution of fluid between intracellular and extracellular compartments is determined mainly by osmotic effects of smaller solutes, especially sodium chloride, acting across the cell membrane. Just as a review, osmosis is the movement of water from areas of low particle concentration to areas of high particle concentration. Cell membranes are relatively impermeable, impermeable to most solutes, but highly permeable to water. Through the aquaporins that we've discussed before, high osmotic pressure can develop across the cell membrane, with small changes in the concentration of solids for each lily Osmo concentration of impermeable solutes, about 19.3mm of mercury of osmotic pressure is exerted on the cell membrane, showing that small changes in permeable solids can cause large changes. Cell volume. Ethnicity refers to whether a solution will cause a change in cell volume. It depends on the concentration of impermeable solids. Isotonic solutions cause neither swelling nor shrinking. Hypertonic solutions have a lower concentration of solutes and will cause water to diffuse into the cell, causing it to swell. Hypertonic solutions will have a higher concentration of solutes, causing water to flow out of the cell and to shrink water. Movement across the cell membrane is so rapid that osmolarity differences are usually corrected within seconds or at most minutes, although water must be absorbed through the gut and transported to different tissues before equilibrium can be obtained, meaning whole body equilibrium is reached about 30 minutes after drinking water. Keep these two principles in mind. Water moves rapidly across cell membrane, and cell membranes are almost completely impermeable to many solids. If isotonic sailing is added to extracellular fluid, the main effect is increased intracellular fluid volume. If hypertonic solution is added to extracellular fluid, extracellular osmolarity is increased and caused osmosis of water out of the cells, which causes increased extracellular volume and cell shrinkage. If hypertonic solution is added. Extracellular fluid osmolarity decreases and causes osmosis of water into the cells, uh, which means both intracellular and extracellular volumes are increased, although intracellular is increased to a greater extent. Rapid changes in cell volume as a result of hyponatremia can affect tissue and organ function, especially the brain. A rapid reduction in plasma sodium concentration can cause brain cell edema and neurologic symptoms. The slow evolution of hyponatremia means the brain and other tissues respond by transferring solutes from the cells into the extracellular compartment. Attenuating the amount of DNA edema created. Hyponatremia can be caused by a loss of water or excess sodium in extracellular fluid. Simple dehydration is the most common cause, but it can. Also be caused by adding sodium chloride to the extracellular fluid. Intracellular edema is caused by hyponatremia, depression of the metabolic systems of the tissues. Lack of adequate nutrition to the cells, and inflammation causing increased membrane permeability. Extracellular edema is caused by abnormal leakage of fluid from the plasma to the interstitial space across the capillaries, and failure of the lymphatics to return fluid from the interstitium back to the blood. There's a good summary of all these on page 316 and 317 and guidance if you want to reference. One of the most serious and common causes of edema is heart failure, which is when the heart fails, pump blood normally, causing increased capillary pressure and increased capillary filtration, while at the same time arterial blood pressure is decreased, causing decreased excretion of salt and water by the kidneys. Typically, sodium chloride remains in the extracellular compartment with only a small amount entering the cells, but when the kidney fails to treat salt and water and large amounts are added to extracellular fluid, it leaks into the interstitial spaces, causing widespread increases in interstitial fluid volume and hypertension. Because of the increase in blood volume, failure to produce normal amounts of proteins, or the leakage of proteins from the plasma causes the plasma colloid osmotic pressure to fall. This leads to increased cartilage operation and extracellular edema. Uh, this can be caused by nephrotic syndrome or cirrhosis of the liver. Safety factors are normally present to prevent edema. Uh, there are low compliance of the interstitium. The ability of lymph flow to increase 10 to 50 fold and wash down the interstitial fluid. Protein concentration, which reduces interstitial fluid colored osmotic pressure as capillary filtration increases. Examples of additional spaces in the body include those listed here. These are typically a thin layer of fluid in the spaces to facilitate sliding. The spaces do not offer much resistance to the passage of fluid, electrolytes, or even proteins, which allows movement back and forth between the spaces and the interstitial fluid. If any of these substances remains in the spaces, it can create osmotic pressure. Um, and a large amount of fluid can diffuse. When edema occurs in the sub case tissue adjacent to the potential spaces. Fluid collects in the potential spaces as well. The phallic vessels typically drain these areas, but a blockage or other abnormality can cause an effusion or a series if it occurs in the. Hey, everyone. This is acid base regulation. All enzyme systems in the body are influenced by hydrogen concentration, and therefore changes alter virtually all bodily functions. The hydrogen ion concentration is normally kept at a low level. For example, sodium levels are about 3.5 million times greater than hydrogen bubbles, so the precision is extremely important. Solutions that donate hydrogen atoms are referred to as actions, whereas a molecule that accepts hydrogen is referred to as a base. Hydrochloric acid donates a hydrogen, therefore it is an acid. Hemoglobin and red blood cells are one of the most important bases in the body. Strong acids and bases. This is so completely and irreversibly. Therefore, the most important bases and acids we will discuss are weak acids and bases. Uh, we will discuss acids and bases more in chemistry and physics in the summer. Uh, so this is, uh, a good primer. Good starter. The dissociation constant is the concentration of acids related to the, uh, concentration of dissociated ions is referred to as k or the power of k over the peak. The reason we use the power of hydrogen, or pH scale, is the normal hydrogen ion concentration is very low in dealing with such small numbers. And all these zeros is cumbersome. pH is the negative log of the hydrogen ion concentration. Uh, as you can see in this formula, arterial pH is normally 7.4. Venus pH is normally 7.35. And to say there is estimated between 6 and 7.4. Intracellular cell metabolism. Cellular metabolism produces CO2, which forms carbonic acid and therefore lowers the pH. There are three primary systems to regulate hydrogen concentration in bodily fluids. The chemical acid base buffer system of the bodily fluids, the rest of which removes CO2 and therefore carbonic acid from extracellular fluid, and the kidneys, which can treat acidic or alkaline beer. Buffer system by the body fluids react with in seconds to minimize acidic changes in the body. The reservoir system acts within a few minutes, and the kidneys, uh, act over a period of hours to days. The kidneys are the slowest to react, but are by far the most powerful pH regulatory mechanisms. A buffer is any substance that can reversibly bind with hydrogen. This comes up with many things, including drugs. If a molecule is bound with another molecule, the effects of the original molecule are removed from the system. Acid is a good example of this in this equation here at the top. When a buffer combines with hydrogen, the effects of the hydrogen are diminished. Another important principle is when any reactant is added to a reversible reaction, it drives the reaction in the opposite direction. This is called love shot in the Ace principle. Uh, no need to learn the name now. I will learn it later. Um. For example, in this uh system, when hydrogen is added, more hydrogen is added. It drives the reaction towards the right. Uh, if you were going to talk about the bicarbonate buffer system, if more hydrogen is added here, it drives, uh, to the left. So we'll drive this way. Um. Examples of the buffer systems in the body are the bicarbonate buffer system and the phosphate buffer system. The bicarbonate system is the combination of CO2 and H2O to form carbonic acid, which reaction is slow except when the enzyme carbonic anhydrase is present. Carbonic anhydrase is especially abundant in the walls of lung alveoli. The epithelial cells of renal tubules, carbonic acid disassociate the hydrogen in by carbon. So if we apply a pencil to this equation and we add more hydrogen to the system, it will drive the reaction to the left producing CO2 and H2O. The amount of bicarbonate is regulated mainly by the kidneys, whereas CO2 is controlled by respiration. Proteins are among the most plentiful buffers in the body because of their high concentration, intracellular hydrogen and bicarbonate diffuse themselves, but CO2 can rapidly diffuse. And of course, if carbonic anhydrase is present, CO2 rapidly becomes hydrogen in the red blood cells. Hemoglobin binds hydrogen and therefore is a buffer. Approximately 60 to 70% of the total chemical buffering of the bodily fluids occurs. Intracellular. The second line of defense for asset based disturbances is control of extracellular fluid CO2 concentration, which, as everyone knows, is eliminated by ventilation. CO2 is produced continually by intracellular metabolic processes. Of course, everyone remembers the Krebs cycle. A 7.4 can be changed to 7.63 by doubling the ventilation rate. The hydrogen ion concentration affects the rate of alveolar ventilation. Hydrogen and bicarbonate are continuously filtered into the renal tubules. The rate of excretion and reabsorption regulates body pH due to a mechanism in the real tubules. The reabsorption of bicarbonate and the excretion of hydrogen are accomplished through the process of hydrogen secretion. Kidneys also produce new bicarbonate when it is needed. 80 to 90% of the bicarbonate absorption and hydrogen secretion occurs in the proximal tubule. You can see in the graph that most of the bicarbonate filtered into the renal tubules is reabsorbed. Bicarbonate ions do not readily diffuse through lipid bilayer or cell walls, so it cannot directly be reabsorbed. Instead, that carbonate combines with hydrogen to form carbonic acid, which dissociates into CO2 and H2O. And as we discussed, CO2 easily diffuses through the big bilayers. Once in the tubular cell, it recombines with H2O under the influence of carbonic anhydrase. Uh, to create a new carbonic acid molecule, which of course, then dissociates in hydrogen and bicarbonate. Um. The bicarbonate is then reabsorbed with sodium bicarbonate cotransporter and a new hydrogen is created. Therefore, each time bicarbonate is reabsorbed into the blood, hydrogen is created. Beginning in the late Mr. tubules. Tubular epithelium secretes hydrogen that primary active transport. Hydrogen is transported by specific proteins utilizing ATP as well as hydrogen potassium counter transporter utilizing ATP as well. This allows the hydrogen ion concentration in the tubular to be increased to as much as 900 fold. As we said before, phosphate and ammonia. Both systems are important in renal tubular system. We will cover this more extensively in renal modules next semester. So we're going to, uh, move through this for now. Restore acidosis. It's caused by damage to restore centers, or any condition that increases the ability of the lungs to eliminate CO2. Referee alkalosis is caused by excessive ventilation. This rarely occurs because of a pathological condition. However, it can occur when a person ascends the high altitude. Low oxygen concentration in the air stimulates respiration, which causes loss of CO2 and mild restoring acidosis. Metabolic acidosis refers to any type of acidosis other than that caused by excessive CO2. Diarrhea is probably the most frequent cause of metabolic acidosis due to the large amounts of sodium bicarbonate and feces. Metabolic alkalosis results from excessive retention of bicarbonate or the loss of hydrogen from the body. It is not nearly as common as metabolic acidosis. Diuretics can increase flow and distorting collecting tubules, causing increased hydrogen secretion and bicarbonate reabsorption. Acid base disorders can be diagnosed by analyzing pH, plasma, uh, bicarbonate, and the concentration of CO2. And I, and gaps are the difference between the measured positively charged cations and the negative charged anions. The normal ranges between 8 and 16. Base. Excessive deficit is the quantity of base that is above or below the normal range. Excess is when there is excess of bicarbonate ions. The use of base excess appears to be superior to measurement of vital signs for rapid physiologic assessment, and a base deficit is becoming increasingly negative is predictive of transfusion requirements. Uh, some of this information is taken from this article that's listed here. Uh, we'll discuss abg's and base deficits more in our synchronous class this week.