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Respiratory Physiology 1 CO2 Transport When oxygen is on the hemoglobin molecule, it is called oxyhemoglobin. Dissociation of oxyhemoglobin is when the oxygen is released and enters the tissues. This dissociation increases as the pCO2 levels increase. In other words, when the carbon dioxide levels rise, oxygen will jump off the hemoglobin and into the tissues. Therefore, the most effective stimulus to the respiratory center is an increase in pCO2. The waste product of cellular respiration is carbon dioxide. CO2 will then attach onto the hemoglobin and be taken to the lungs to be expelled. 2 CO2 Transport CO2 is carried to the lungs on the hemoglobin, after the oxygen has left to enter the tissues. The carbon dioxide reacts with water in the RBC to form carbonic acid, which then breaks apart into a hydrogen ion (which lowers blood pH) and a bicarbonate ion (which raises blood pH). CO2 + H2O H2CO3 H+ + HCO3- This reaction is reversible, and would go mainly to the right in the tissues and to the left in the lungs. CO2 is transported in the blood predominately in the form of bicarbonate. The number of H+ ions in the blood depends partly on the amount of CO2 in the blood. The more CO2 in the blood, the more H+ in the blood, which makes the blood acidic. If the blood is too acidic, bicarbonate ions are absorbed to raise the pH. If the blood is to alkaline, bicarbonate ions are excreted by the kidneys. 3 Respiratory System Contribution to pH Balance in the Blood If a person has excess H+ ions in the blood (acidosis), they will breathe more rapidly. If the person has an airway obstruction (such as asthma), they cannot exhale the excess CO2. Because the H+ are building up, the carbonic acid will also build up, causing a drop in pH (acidosis) in the blood. Enzymes in the body cannot work outside of their optimal pH range, so chemical reactions come to a halt. Hyperventilation results in too little CO2 in the blood, so the person has a high pH (alkalosis), which also 4 denatures enzymes. Control of Respiration Relaxed breathing only requires the diaphragm to contract for inspiration, and for the diaphragm to relax for expiration. Forced breathing requires the diaphragm plus muscles that raise and lower the ribs (external intercostals for inspiration, internal intercostals for expiration). The respiratory centers are most sensitive to the level of CO2 in the blood, rather than the levels of oxygen. 5 Control of Gas at Cellular Level The flow of blood through capillaries is controlled by sphincters on the arterioles and capillary beds to adjust the amount of blood flowing to particular tissues. Cells and tissues that are undergoing increased aerobic activity have less oxygen and more CO2, lower pH, and increased temperature. When the CO2 levels in the tissues are too high, the smooth muscle sphincters relax to allow more blood flow to increase gas exchange. 6 Boyle's Law P1V1=P2V2 Pressure and volume are inversely related (if other variables are kept constant.) Boyle’s Law assumes normal circumstances, not a person who is in high altitude or who has variation in body temperature. 7 Air Pressure in Lungs Every time a molecule strikes the wall of a container, it causes pressure. In a larger container with fewer molecules, it takes a while to strike the wall randomly, so there is less pressure. The number of impacts on a container wall is the pressure. The lungs must have a volume change to create a pressure change, which is required to have air move into and out of the lungs. 8 Air Pressure in Lungs The diaphragm is the muscle that mostly contributes to the volume change. When it contracts, it pulls downward, and the volume of the thoracic cavity increases. The external intercostals elevates the ribcage, giving the lungs more room, so they also increase the lung volume. Those two muscles cause increased volume. 9 Air Pressure in Lungs Because the lungs are tethered to the thoracic cavity, when your chest wall expands, your lungs expand with it. The lungs are stuck to the chest wall because the serous fluid in the pleural cavity makes the lungs stick to the chest wall like two pieces of wet glass stuck together. When the lungs expand, their volume expands. That means there is less pressure in the lungs than there is in the outside air. Since air moves from high to low pressure, air flows into the lungs. As air flows in, the alveoli expand, so the volume in each air sac expands, so the pressure in the alveoli lowers. Air in the conducting passages (bronchi) is at higher pressure, so it will move from high to low pressure 10 areas. Therefore, air will move into the alveoli. Air Pressure in Lungs We are looking at two types of air pressures: atmospheric pressure, and the pressure of air deep in the lungs, called the alveolar (pulmonary) pressure. As long as there is a difference in pressure between these two, there will be a pressure gradient, and air will flow. If they equal each other (such as during a punctured lung, called a pneumothorax), air will not flow. 11 Left shift CAUSE: pH increased CO2 decreased Temperature decreased CAUSE: pH decreased CO2 increased Temperature increased 12 Right shift CAUSE: pH increased CO2 decreased CAUSE: pH decreased CO2 increased 13 Shifts A left shift will increase oxygen's affinity for hemoglobin. In a left shift condition (alkalosis, hypothermia, etc.) oxygen will have a higher affinity for hemoglobin (it won’t leave!). This can result in tissue hypoxia even when there is sufficient oxygen in the blood. A right shift decreases oxygen's affinity for hemoglobin. In a right shift (acidosis, fever, etc.) oxygen has a lower affinity for hemoglobin. Blood will release oxygen more readily. This means more O2 will be released to the cells, but it also means less oxygen will be carried from the lungs in the first place. 14 What happens if the lung dissociates from the chest wall? Pneumothorax: air in the pleural cavity Hemothorax: blood in the pleural cavity How? Injury (Gun shot, stabbing) Spontaneous (tissue erosion, disease lung) Bleeding wound Chest wall recoils outward (barrel chest) Lung recoils inward (atelectasis = alveolar, lung collapse) 15 Emphysema COPD (chronic obstructive pulmonary disease) is emphysema plus chronic bronchitis. Emphysema is generally caused by smoking. The alveoli have broken, leaving spaces where gas exchange cannot take place. Compliance decreases, so It is difficult to expel the air in the lungs. Each inhalation is a forced inspiration also. When the ribs are continually raised with each breath, they eventually remain in the upright position, causing a barrel chest. 16 Exhalation Problem: COPD Normal exhalation is passive, requires no ATP. But forced expiration (such as emphysema patient) recruits abdominal muscles. The muscles enlarge with time, creating a barrelshaped chest, typical of emphysema patients and COPD. 17 COPD In everyone, the midsized bronchioles do not have cartilage rings to hold them open, and during exhalation, the sides of the bronchioles collapse and touch each other. If there is not enough surfactant, they stick to each other with greater strength (like two wet pieces of glass), and the person has to forcefully exhale with each breath to overcome the cohesiveness of the fluid. Surfactant is like adding soap to the fluid so the surfaces come apart easier. 18 Exhalation Giving oxygen in high concentration helps get air into their lungs, but it reduces the drive for them to breathe. CO2 is a powerful driving force for ventilation. When a person has COPD, they have less CO2, and oxygen becomes the driving force. If we give them oxygen, the drive for them to breathe becomes diminished. They eventually wind up on a positive pressure ventilator, but the disease progresses, and they die from suffocation. 19 Acute Mountain Sickness (Altitude Sickness) When you visit someone in a high elevation (5,000 m) you might get acute mountain sickness. Symptoms: Cause: Severe headache, fatigue, dizziness, palpitation and nausea. Pulmonary edema. Why do you get pulmonary edema? High elevations have lower pO2 levels. This causes hypoxia (lack of oxygen) in the pulmonary capillaries This causes increased pulmonary arterial and capillary pressures (pulmonary hypertension) That causes the pulmonary edema 20 Ventilation Volume When you breathe in, you inhale about 500 ml. You exhale about 500 ml. Therefore, 500 ml is your TIDAL VOLUME. Not all 500 ml gets down deep to your alveoli. About 150 ml of it stays in the conductive zone (bronchi and trachea). About 350 ml reaches the alveoli. That is considered your alveolar ventilation volume. That is the amount of air that can undergo gas exchange. If you want to calculate how much air moves in and out per minute, take the tidal volume and multiply it by breathing rate (about 12 breaths per minute for adult, 20 for children). 500 x 12 = total ventilation Tidal volume – 150 x 12 = alveolar ventilation 21 Obstructive Lung Diseases Obstructive lung diseases are characterized by inflamed and easily collapsible airways, obstruction to airflow, and frequent hospitalizations. Examples Asthma Bronchitis Chronic obstructive pulmonary disease (COPD) 22 Restrictive Lung Diseases These are extrapulmonary or pleural respiratory diseases decreased lung volume (rapid, shallow breathing), an increased work of breathing, and inadequate ventilation and/or oxygenation. Decreased vital capacity. that restrict lung expansion, resulting in a Cystic Fibrosis Infant Respiratory Distress Syndrome Weak respiratory muscles Pneumothorax 23 Capacities are two or more volumes added together 24 You don’t need to memorize the normal numbers, just the definitions Respiratory Cycle: A single cycle of inhalation and exhalation Respiratory rate: number of breaths per minute (usually about 12-18; children higher 18-20). Tidal Volume: normal breath in and out. Usually about 500 ml. Inspiratory Reserve Volume: take in a normal breath, stop, now inhale as much more as you can. In other words, this is the amount of air that can be forcefully inhaled after a normal inhalation. This is your tidal volume in plus your inspiratory volume. Expiratory Reserve Volume (Expiratory capacity): take a normal breath in, a normal breath out, then breathe out the most you can. In other words, this is the amount of air that can be forcefully exhaled after a normal exhalation. This is the air needed to perform the Heimlich maneuver. The maneuver decreases the thoracic cavity volume, causing increased pressure in lungs. That causes forced air with high pressure to be expelled from the lungs. Residual volume: The amount of air left in your lungs after you exhale maximally. This air helps to keep the alveoli open and prevent lung collapse. This is estimated based on height and age 25 You don’t need to memorize the normal numbers, just the definitions Vital capacity: The volume of air a patient can exhale maximally after a forced inspiration. Maximum deep breath in, then exhale as much as possible. It can be used to determine if problems are obstructive (normal) or restrictive (reduced). Vital capacity divided by expiratory reserve volume should be 80%. Total Lung Capacity (TLC): the sum of all lung volumes Inspiratory Capacity: amount of air for a deep breath in after normal exhalation Functional residual capacity: amount of air left in your lungs after a normal exhale. You have to calculate this: FRC = ERV + residual volume. In COPD, their FRC increases. They have a barrel chest The lungs don’t have as much recoil, have decreased tidal volume, cannot exhale enough 26 You don’t need to memorize the normal numbers, just the definitions Dead Space: Area where air fills the passageways and never contributes to gas exchange. Amounts to about 150 ml. Minute Respiratory Volume (MRV): tidal volume x respiratory rate. This calculation does not take into account the volume of air wasted in the dead space. A more accurate measurement of respiratory efficiency is alveolar ventilation rate. Alveolar Ventilation Rate (AVR) AVR = (TV – Dead Space) x Respiratory Rate Summary of lung calculations FRC = ERV + RV TLC = RV + ERV + TV + IRV MRV = TV x RR AVR = (TV – Dead Space) x RR You DO need to know these formulas. 27 Sample Questions Minute Respiratory Rate is the volume of air that enters the airways (passes the lips) each min. MRV = Tidal volume x rate of breathing = (500 ml/breath) x 12 breaths/min = 6,000 ml/min Alveolar ventilation rate is the volume of air that fills all the lung’s respiratory airways (alveoli) each min. In a normal, healthy lung, this might be: AVR = (tidal volume – dead space volume) x rate of breathing = (500 ml/breath – 150 ml) x 12 breaths/min = (350 ml/breath) x 12 breath/ min = 4, 200 ml/min In a diseased, poorly perfused lung, this value may well be much lower. Then, is panting an example of hyper, normal, or hypoventilation???? 28 Respiratory vs. Metabolic Acidosis and Alkalosis RESPIRATORY ACIDOSIS AND ALKALOSIS is abnormal blood pH which is caused by abnormal breathing rates. It is not necessarily a disease, since hyperventilating from stress is not a disease. Respiratory alkalosis is caused by hyperventilation. This increases the amount of CO2 that you are exhaling. CO2 is an acid, so if you hyperventilate, you are exhaling a lot of acid, so your blood plasma pH will increase (alkalosis) Respiratory acidosis is caused by hypoventilation. This decreases the amount of CO2 that you are exhaling. If you hypoventilate, you are not exhaling enough acid, so your blood plasma pH will decrease (acidosis). Respiratory acidosis can also be caused by interference with respiratory muscles by disease, drugs, toxins. METABOLIC ACIDOSIS AND ALKALOSIS is abnormal blood pH which is not caused by abnormal breathing rate. Metabolic acidosis can be caused by Salicylate (aspirin) overdose Untreated diabetes mellitus (leading to ketoacidosis) Metabolic alkalosis can be caused by excessive vomiting (loss of acid from stomach) 29 Compensations for Respiratory vs. Metabolic Acidosis and Alkalosis Respiratory alkalosis can be compensated by excreting an alkaline urine Respiratory acidosis can be compensated by excreting an acidic urine Cannot hypoventilate since hyperventilation is the problem in the first place! Cannot hyperentilate since hypoventilation is the problem in the first place! Metabolic acidosis can be compensated by excreting an acidic urine hyperventilation Metabolic alkalosis can be compensated by Excreting an alkaline urine Hypoventilation 30 Acid-Base Conditions Excessive diarrhea Causes the problem of low HCO3 (bicarbonate) Leads to pH in blood (acidosis) Lungs Compensate by: pCO2 (hyperventilation, which decreases the CO2 content in the blood, thereby removing acid from the blood) Kidneys can also compensate by increasing bicarbonate reabsorption. 31 Acid-Base Conditions Ingesting excessive stomach antacids Causes the problem of high HCO3 (bicarbonate) Leads to pH in blood (alkalosis) Lungs Compensate by: pCO2 (hypoventilation, which increases the CO2 content in the blood, thereby adding acid from the blood) Kidneys can also compensate by increasing acid secretion. 32 Acid-Base Conditions Aspirin overdose Causes the problem of high acid, low HCO3 (bicarbonate) Leads to pH in blood (acidosis) Lungs Compensate by: pCO2 (hyperventilation, which decreases the CO2 content in the blood, thereby removing acid from the blood) Kidneys can also compensate by increasing bicarbonate reabsorption. 33 Acid-Base Conditions Hyperventilation from fear or pain Causes the problem of pH in blood (alkalosis) from CO2 being exhaled. The lungs are the problem, so the lungs cannot compensate. However, the kidneys can compensate by: HCO3 secretion, which increases the concentration of acid in the blood. 34 Pulmonary Embolism Pulmonary Embolism: blockage of the pulmonary artery (or one of its branches) by a blood clot, fat, air or clumped tumor cells. The most common form of pulmonary embolism is a thromboembolism, which occurs when a blood clot, generally in a vein, becomes dislodged from its site of formation, travels to the heart, goes into a pulmonary artery, and becomes lodged in the smaller artery in the lungs, blocking blood flow and oxygen to that region of the lung. Symptoms may include difficulty breathing, pain during breathing, and possibly death. Treatment is with anticoagulant medication. 35 Renal Physiology PART ONE Renal Physiology Overview PART TWO Renal Clearance PART THREE Renal Acid-Base Balance 36 Role of Kidneys The kidneys can adjust blood volume, blood pressure, and blood composition BLOOD VOLUME Adjusts the volume of water lost in urine by responding to ADH, aldosterone, and renin BLOOD PRESSURE Releasing renin and adenosine (increases blood pressure) BLOOD COMPOSITION Releasing erythropoietin (increases RBC production) 37 Sympathetic Nervous System Effect on Kidneys Changes the rate of blood flow (and therefore, the pressure) to the glomerulus by telling the precapillary sphincters when to contract or relax. Sympathetic nervous system is stimulated by renin, which is released by the kidney. Causes changes in water and sodium reabsorption by the nephron 38 pH Imbalances Many things can alter the pH of the blood Beverages we drink Acids produced by metabolism Breathing rate Vomiting (loss of acid) Diarrhea (loss of base) pH imbalances are dangerous because many enzymes only function within a narrow pH range. 39 Renal Physiology Basic Mechanisms of Urine Formation 1) 2) 3) 4) Glomerular filtration Tubular reabsorption Tubular secretion Excretion How do we determine these rates? Master formula 40 Glomerular Filtration The capillaries in the glomerulus contain many holes, called fenestrations. As blood passes through the glomerulus, the plasma passes through the fenestrations. Proteins and other large substances do not cross through; they stay in the bloodstream. The filtered plasma leaves the bloodstream in this way, and enters the glomerular capsule, and then enters the proximal convoluted tubule. 41 Glomerular Filtration Rate GFR is used as a measure of kidney function. Normal GFR is 125 ml per minute for both kidneys combined. That means 7.5 liters per hour, or 180 liters per day. That is 45 gallons of filtrate produced per day! Of course, most of that is reabsorbed. Average urine output is about 1.2 liters per day. That means you need to drink 1.2 liters of fluid per day (remember that caffeine and alcohol are diuretics, so you need more than that to compensate if you drink those beverages). You need to drink more (about 2 liters per day) if you are getting a cold or flu. 42 Altering GFR Several different mechanisms can change the diameter of the afferent and efferent arterioles to alter the GFR: Hormonal (hormones) Autonomic (nervous system) Autoregulation or local (smooth muscle sphincters around the arterioles or capillaries near the glomerulus) 43 Remember the route the fluid takes: Glomerulus Proximal convoluted tubule (PCT) Descending limb of LOH Ascending limb of LOH Convoluted tubule Collecting duct Tubular Reabsorption This is the process by which substance in the renal tubules are transferred back into the bloodstream. Reabsorption is the removal of water and solute molecules from filtrate after it enters the renal tubules. Fluid goes from the glomerulus to the proximal convoluted tubule (PCT), down the loop of Henle and back up, then into the distal convoluted tubule (DCT), and into the collecting duct. In the PCT, the nutrients are reabsorbed. If there are more nutrients than can be reabsorbed (such as excess sugar), it will be excreted in the urine. When the nutrients are reabsorbed (in the PCT), the inside of the tubule will have more water and less nutrients. Since water goes to the area that has a higher concentration of particles (osmosis), water will also leave the tubules; this occurs in the DCT. By the time the fluid has reached the collecting duct, nothing but 45 waste products are left, such as urea, ammonia, and bilirubin. Tubular Reabsorption Capillaries follow the renal tubules and wrap around them. The straight capillaries that travel longitudinally next to the tubules are called vasa recta, and the capillaries that wrap around the tubule are called peritubular capillaries. There is a space between the capillaries and the tube, called the peritubular space. 46 Tubular Reabsorption Tubular Cells Peritubular Capillaries Filtrate arriving from Bowman’s Capsule Lumen of Tubule The peritubular capillaries are nearby, and the particle concentration is low inside of them. Therefore, the particles in the peritubular space (high concentration of particles) will leave that space and enter into the peritubular capillaries by osmosis. That is how the nutrients are reabsorbed from the tubules back into the bloodstream. 47 Tubular Reabsorption The ascending limb of the Loop of Henle and the DCT are impermeable unless hormones cause substances to be moved through their walls. If the blood is low in sodium, (after excessive sweating), aldosterone (from the adrenal cortex) will cause more sodium to be pumped out of the tubule and into the peritubular space. The sodium will then enter the capillaries. Since water follows where salt goes, whenever the body needs more water (such as dehydration), ADH is released (from the neurohypophysis = posterior pituitary). ADH is also called vasopressin. Aldosterone and ADH will increase blood volume, increasing blood pressure. These two hormones begin their action in the ascending limb and continue to work in the DCT. 48 Tubular Secretion Some substances are unable to filter through the glomerulus, but are not wanted by the body. Examples are pollutants like pesticides, and many drugs, such as penicillin and non-steroidal anti-inflammatory drugs (NSAID’s). As blood passes through the peritubular capillaries, those substances are moved from the capillaries directly into the PCT and DCT. This is called tubular secretion. 49 Juxtaglomerular Apparatus The distal end of the renal tubule passes next to the glomerulus to form the juxtaglomerular apparatus (juxta means “next to”). 50 Juxtaglomerular Apparatus: Alters BP and GFR by autoregulation Two types of cells: 1) Macula densa cells 2) Juxtaglomerular cells 51 Juxtaglomerular Apparatus: Macula Densa Cells If blood pressure is too low, the macula densa releases adenosine, which causes vasoconstriction of the afferent arteriole. This will slow the GFR, so less water is lost, and blood pressure increases. 52 Juxtaglomerular Apparatus: Macula Densa Cells If blood pressure is too high, the macula densa stops releasing adenosine, which allows the sphincters to relax. This will increase GFR so more water is lost, and blood pressure decreases. 53 Juxtaglomerular Apparatus: Juxtaglomerular Cells Juxtaglomerular cells secrete renin if the blood pressure is still too low after adenosine has caused vasoconstriction. Renin causes more sodium to be reabsorbed, and water follows, so blood volume increases, so blood pressure increases. 54 Summary of Autoregulation The nephron can alter the blood pressure and flow into the glomerulus by autoregulation. The JGA senses the blood pressure going into the glomerulus and the flow rate of the fluid going through the renal tubule. If the GFR is too low, the JGA (macula densa) will cause the pre-capillary sphincters on the nearby arterioles to contract, increasing blood pressure, like turning up the faucet on a hose. If that restores the desired filtration rate and flow, no further action is needed. If not, the kidneys produce the enzyme renin, which makes the lungs produce angiotensin converting enzyme (ACE), which turns A1 into A2, which constricts blood vessels, and also causes the release of aldosterone, raising the blood pressure. 55 Hormonal Regulation If a person sweats from activity, eats very salty food, or has diarrhea, it changes the sodium and water content of the plasma. Two hormones that affect the ascending limb of the Loop of Henle are aldosterone and antidiuretic hormone (ADH). Adosterone is produced by the adrenal cortex and causes additional sodium ions to be pumped our of the tubule and into the bloodstream. Water comes with it by osmosis, and the blood pressure increases. ADH is produced by the posterior pituitary gland and causes retention of additional water from the DCT and collecting ducts. Sodium is not included in this process, so the result is to dilute the plasma during dehydration, when the plasma is becoming to concentrated with particles. 56 Erythropoietin The kidneys also monitor the oxygen content of the blood. If O2 levels are low, the JGA releases erythropoietin to stimulate the bone marrow to produce more red blood cells. 57 Neural Regulation The kidneys receive about 22% of the blood pumped out of the heart, so that is a substantial quantity passing through the kidneys at any given time. If there is a stressor and the sympathetic nervous system causes us to go into fight or flight mode, the skeletal muscles need to have a maximum amount of blood flow. Neurons from the sympathetic nervous system innervate the kidneys to decrease renal blood flow during critical situations. 58 Urine Urine contains ions such as sodium, chloride, and potassium, as well as suspended solids, known as sediments, such as cells, mineral crystals, mucus threads, and sometimes bacteria. The pH of urine is normally 4.6-8 A urinalysis can identify abnormal processes occurring in the body. Because urine is a waste product, its contents are influenced by the foods and drinks we ingest. We may lose fluid elsewhere, such as through sweating or diarrhea, which causes the urine to become more concentrated. Acids produced through metabolism can also change the pH of our urine. Even changes in breathing rate can change the urine pH as excess acids or bases are excreted to maintain normal plasma pH. 59 Abnormal Urinalysis These substances should not be in the urine. When they are, it is abnormal. Glucose Blood Protein Pus Bilirubin Ketones 60 Causes of abnormal UA Glucose: diabetes mellitus Blood: bleeding in urinary tract from infection or kidney stone Protein: kidney disease, hypertension, excessive exercise, pregnancy Pus: bacterial infection in urinary tract Bilirubin: liver malfunction Ketones: excessive breakdown of lipids 61 Micturition Urination is technically known as micturition. Once the volume in the urinary bladder exceeds 200 ml stretch receptors in its walls send impulses to the brain, indicating the need to eliminate. When you make the decision to urinate, the parasympathetic nervous system stimulates the smooth muscle in the urinary bladder’s internal sphincter to contract. Remember, the internal sphincter is smooth muscle (involuntary) and the external sphincter is skeletal muscle (voluntary). Both must relax for urine to exit. 62 Diuretics for hypertension and congestive heart failure Diuretics decrease plasma volume. This group of drugs are thiazide diuretics (such as Lasix). They inhibit the reabsorption of sodium and potassium from the renal tubule, causing more water to pass out as urine. Compared to sodium, the homeostatic range of potassium is quite narrow. Lasix (Furosemide) inhibits reabsorption of potassium more than other diuretics. Low blood levels of potassium are called hypokalemia. It is important for someone on Lasix to take potassium supplements or eat fruits or vegetables that have a lot of potassium (such as cantaloupe). However, too much potassium from excessive supplements can have fatal side effects. 63 Diuretics Furosemide (Lasix) Mannitol Spironolactone Amiloride 64 Homeostasis Maintaining the proper concentration of sodium and water is critical. If the plasma is too concentrated with particles, nearby cells can shrink and lose their function. If the plasma is too dilute, water can enter the nearby cells and cause them to expand, also decreasing their function. This is especially dangerous in the brain. Studies have shown a close link between obesity, diabetes, and kidney disease. Exercise helps maintain normal kidney function by increasing blood flow, and it decreases the incidence of high blood pressure. People receiving dialysis and those who have had kidney transplants especially need to exercise. 65 Renal Physiology PART TWO Renal Clearance 66 How to calculate Tubular Load If we want to know how much glucose was filtered into the nephron, we need to know that person’s blood plasma glucose levels, and we would need to calculate their GFR. Each individual solute will have its own tubular load calculation. TL glucose = Pglucose x GFR TL sodium = Psodium x GFR chloride = Pchloride x GFR TL Renal Equations For any substance, The rate of excretion = rate of + filtration (Urinary output) (GFR or TL) rate of – secretion rate of reabsorption Other terms that are used to express these ideas: •For “Rate of excretion” we often use the term “urinary output” •For “Rate of filtration,” when referring to filtered fluid, we often use the term GFR (glomerular filtration rate) if referring to filtered solute, we use TL (Tubular Load) 68 Solutes are reabsorbed into the blood stream The next photo is of a Proximal Convoluted Tubule (PCT), just beyond the glomerulus. The lumen of the tubule contains the filtrate which leaked out of the capillaries and into the glomerulus, entered Bowman’s capsule, and has now arrived in the PCT. There are cells (tubular cells) lining the lumen of the PCT. The cells have proteins that allow some solutes to diffuse into the cell, and right back out cell, and into the peritubular capillaries that surround the PCT. In that way, solutes re-enter the blood stream. 69 Filtrate arriving from Bowman’s Capsule Peritubular Capillaries Tubular Cells Lumen of PCT 70 Peritubular capillaries 71 Proximal Convoluted Tubule Water will follow the solutes. The PCT is the biggest site for reabsorption of solutes (substances dissolved in water). 100% of glucose and amino acids are reabsorbed in the PCT. 67% of Na and water are reabsorbed here. If ADH levels are very high, most of the water will be reabsorbed in the PCT. Water reabsorption along the proximal convoluted tubule (PCT) occurs by osmosis resulting primarily from reabsorption of sodium 72 Proximal Convoluted Tubule In a state of acidosis, the PCT will secrete H+ ions. When the H+ ions are secreted, reabsorption of bicarbonate ions occurs at the same time. H+ ions are also secreted in the DCT, but bicarbonate cannot be reabsorbed there. 73 Glucose reabsorption Glucose and amino acids leave the tubule and enter the peritubular capillaries. That is reabsorption. When any substance leaves the bloodstream and enters the lumen of the kidney tubules, it is secretion. By adjusting reabsorption and secretion, your body adjusts its acid-base balance; if too many H+ ions were kept in the plasma, there is too much acid, and the H+ ions will start to be secreted more. 74 Transport Maximum When proteins are shuttling solutes, the rate of this shuttling has a maximum, called a transport max (Tm). If there are more solutes present than can be transported, the solutes will end up in your urine. There will be a point at which you can saturate these transporters. For instance, when your blood glucose levels are elevated because you have a problem making insulin or responding to insulin, then you will have an increase in glucose load in Bowman’s capsule. This excess filtered load will cause a spill of glucose into the urine. After the PCT, there are no more glucose transporters to reabsorb it. 320 is the max rate to filter glucose. If you filter 125 and reabsorbed 125, how much did you excrete? None. If you filter 375 but reabsorb 320 (transport maximum), 55 is excreted 75 Threshold Transport maximum is the total transport maximum throughout all of the nephrons in the kidney. They do not all have the exact number and type of transporters. One single nephron might get to maximum and a tiny amount of glucose will appear in the urine. As more nephrons reach their maximum, more glucose will appear in the urine. That appearance of glucose in the urine before you reach the overall Tm of the kidney is called threshold. Threshold is the plasma concentration at which a substance begins to appear in the urine 76 =solute = transporter 1 5/min 2 3 4 5 Transport maximum is reached when carriers are saturated. 77 =solute Excretion = transporter 1 5/min 2 3 4 5 Transport maximum is reached when carriers are saturated. 78 Calculate Glucose Excretion Step 1: Calculate their filtered load: GFR x plasma glucose level 90 x 2 Step 2: Determine reabsorption of glucose (maximum is 150). Step 3: Subtract 150 from 180, and that tells you their excretion. Excretion = filtration – reabsorption Answer 180 – 150 = 30 mg/min 79 A patient with uncontrolled diabetes has a GFR of 90 ml/min, a plasma glucose of 2mg/ml, and a transport max (Tm) shown in the figure. What is the glucose excretion for this patient? 250 (mg/min) 200 Glucose a. 0 mg/min b. 30 mg/min c. 60 mg/min d. 90 mg/min e. 120 mg/min Transport Maximum (150 mg/min) Reabsorbed 150 100 Excreted . 50 Threshold 0 50 100 350 Filtered 150 200 Load of Glucose (mg/min) Copyright © 2006 by Elsevier, Inc. 250 300 80 Answer: Excretion = filtration (GFR x Pglu) – reabsorption (Tmax) 180 – 150 = 30 mg/min 250 GFR = 90 ml/min PGlu = 2 mg/ml Tmax = 150 mg/min (mg/min) 200 Glucose a. 0 mg/min b. 30 mg/min c. 60 mg/min d. 90 mg/min e. 120 mg/min Transport Maximum (150 mg/min) Reabsorbed 150 100 Excreted . 50 Threshold 0 50 100 350 150 200 250 300 Filtered Load of Glucose Copyright © 2006 by Elsevier, Inc. (mg/min) 81 A patient with uncontrolled diabetes has a GFR of 90 ml/min, a plasma glucose of 2.33mg/ml, and a transport max (Tm) shown in the figure. What is the glucose excretion for this patient? 250 (mg/min) 200 Glucose a. 0 mg/min b. 30 mg/min c. 60 mg/min d. 90 mg/min e. 120 mg/min Transport Maximum (150 mg/min) Reabsorbed 150 100 Excreted . 50 Threshold 0 50 100 350 Filtered 150 200 Load of Glucose (mg/min) Copyright © 2006 by Elsevier, Inc. 250 300 82 Answer: Excretion = filtration (GFR x Pglu) – reabsorption (Tmax) 210 – 150 = 60 mg/min 250 GFR = 90 ml/min PGlu = 2.33 mg/ml Tmax = 150 mg/min (mg/min) 200 Glucose a. 0 mg/min b. 30 mg/min c. 60 mg/min d. 90 mg/min e. 120 mg/min Transport Maximum (150 mg/min) Reabsorbed 150 100 Excreted . 50 Threshold 0 50 100 350 150 200 250 300 Filtered Load of Glucose Copyright © 2006 by Elsevier, Inc. (mg/min) 83 Urea Urea is also reabsorbed in the PCT. This happens because its concentration in the tubule is high, so it diffuses down its concentration gradient, which means it will leave the tubule and enter the capillaries. This is an advantage because it is a particle, and it brings water with it. But urea is a waste product…how will we get rid of it? We will reabsorb it now and secrete it again further along in the nephron. By the time the reabsorbed urea travels in the vasa recta to the distal convoluted tubule, its concentration is higher in the bloodstream than it is in the tubule, so it diffuses back out of the capillaries and into the tubule to be excreted. The DCT is impermeable to water, so water does not follow it. 84 Diuretics in the PCT Lasix Mannitol cause diuresis by reducing net water reabsorption from the proximal convoluted tubule “Potassium sparing” refers to a diuretic’s tendency to decrease potassium excretion 85 Diuresis in the PCT Diuresis means the person is excreting a lot of water. This is what happens in diabetes mellitus (and insipitus). It makes the person thirsty, so they drink a lot of water. However, that is not why they have diuresis. The reason for the diuresis is the large amount of glucose in the tubule draws water with it, since glucose is a particle. Thus, the large filtered load of glucose has an osmotic effect on the tubule 86 Now we leave the PCT and enter the Loop of Henle Our kidneys are responsible for adjusting the urinary output. They are responsible for determining if you have a lot of urine which very dilute, or scant, concentrated urine. If you drink a lot of water, it will make your urine dilute (more water than solutes). If you are dehydrated, your urine will be concentrated (more solutes than water). Caffeine and alcohol are dehydrating, so they have the opposite effect of drinking water. They block antidiuretic hormone (ADH) too. 87 Before we move onto the Loop of Henle, be mindful of the following: How can you make a solution more concentrated? Take out water or add more solute. How can you make a solution less concentrated? Add water or take out more solute. Your kidneys play that game. To do that, we have to separate solutes and water. But how do we do that, since water follows particles? There are several parts of the nephron that are impermeable to water. 88 LOOP OF HENLE: Ascending Limb Impermeable to water, so no water is reabsorbed or secreted. Permeable to NaCl and urea: NaCl (or sodium and chloride separately) diffuses out of tubule (reabsorbed) Urea diffuses into tubule (secreted) 89 Saltiness in the LOH Now let’s take the LOH together: on the descending limb we have water leaving and salt entering the lumen. On the ascending limb, we have salt leaving, and no more water leaving the lumen. As it goes up the ascending limb, it is becoming more and more hypo-osmotic (less and less salty). At the top of the ascending limb, it tastes less salty than blood plasma. Now we leave the LOH and enter the distal convoluted tubule (DCT) 90 Distal Convoluted Tubule (DCT) 5% more sodium is reabsorbed The DCT activity can be influenced by hormones. If there are no hormones around, these cells don’t do anything; whatever is remaining in the lumen will go into the bladder. If there are no hormones, the last 13% of water and the last 3% of Na goes into the toilet. Anti-diuretic hormone (ADH) and aldosterone will cause more water and salt to be reabsorbed (raises blood pressure). 91 Distal Convoluted Tubule (DCT) Special cells in the DCT, called intercalated cells manage your acid-base balance, to secrete more H+. If you are in a state of acidosis (too much acid in your blood) because you drank alcohol, your intercalated cells will secrete more H+ to bring the pH back to normal. If you are in a state of alkalosis because you have been hyperventilating (breathing fast), will the intercalated cells increase H+ reabsorption or H+ secretion? Answer: increase H+ reabsorption. 92 Secretion Secretion is the opposite of reabsorption. Any time you see a solute going from the tubular cells and into the lumen, it is called secretion. Secreted substances end up in the urinary bladder. It happens by active transport. We secrete acids, bases, phosphates, excess potassium. Secretion works this way: solutes diffuse out of the peritubular capillary bed and into the tubular cells, then they enter lumen of the convoluted tubule. From there, they go out the collecting duct, and into the urinary bladder. 93 Long-Term Dehydration Compensations in a dehydrated person who is deprived of water for 36 hours include the following: increased plasma renin increased plasma ADH decreased concentration of plasma atrial natriuretic hormone (vasodilator made by the heart; increases diuresis) increased water permeability of the collecting duct decreased water permeability in the ascending loop of Henle 94 Hormones affecting the kidney Renin: released by kidney when blood pressure is too low ACE: Pulmonary capillary enzyme that responds to renin. When renin is elevated, it cleaves angiotensin I into angiotensin 2. Angiotensin II: causes blood vessel constriction to increase blood pressure. It also stimulates the release of aldosterone. Aldosterone: Secreted from the zona glomerulosa of the adrenal cortex. It increases blood pressure by increasing sodium reabsorption. It is primarily released due to elevated potassium levels. ADH: Promotes aquaporin insertion in the cell membranes of the tubules Aquaporin is a protein that allows water to pass through the cell membrane, to be absorbed out of the tubule. Atrial natriuretic peptide (ANP): heart hormone that promotes more diuresis and urine production to lower blood pressure. Adenosine: Macula densa use this to molecule to change the radius of the afferent arteriole. 95 Clinical Correlations What are the symptoms of severe dehydration? 1. Disoriented 2. Falls unconscious 3. Measurable loss of weight during strenuous activity (water loss) 4. Blood pressure drops 96 Clinical Correlations A marathon runner becomes dehydrated during a race. 1. What will happen to their weight? 2. What will happen to blood volume? 3. What will happen to blood pressure? 4. What will happen to heart rate? 5. What will happen to their baroreceptors? 6. What will happen to sympathetic outflow? 97 Clinical Correlations A marathon runner becomes dehydrated during a race. 1. Weight goes down (water loss) 2. Blood volume decreases (water loss) 3. Blood pressure decreases (volume loss) 4. Heart rate increases (b/c of decreased BP) 5. Baroreceptors decrease firing (low BP) 6. Sympathetic outflow increases (to 98 compensate) Clinical Correlations A marathon runner becomes dehydrated during a race. 1. What will happen to their Renal blood flow (RBF)? 2. What will happen to their tubular load of sodium? 99 Clinical Correlations A marathon runner becomes dehydrated during a race. 1. Renal blood flow (RBF) will decrease The body does not want to lose more water 2. Tubular load of sodium will decrease Sodium is reabsorbed so water will come with it 100 Clinical Correlations A marathon runner becomes dehydrated during a race. 1. What hormones would compensate for this condition? These would all be elevated: Renin Angiotensin II Aldosterone ADH 101 Clinical Correlations A marathon runner becomes dehydrated during a race. 1. What will be the urinary output? Low volume 2. What will be the urine concentration? High concentration 102 Clinical Correlations A marathon runner becomes dehydrated during a race and falls unconscious. 1. What type of shock is this? Hypovolemic shock 2. What is the treatment? I.V. saline/bicarbonate solution Giving saline will increase water retention Giving bicarbonate will reduce acidosis 103 Clinical Correlations A marathon runner becomes dehydrated during a race and falls unconscious. 1. Why do they have acidosis? Hypovolemic shock reduces oxygen delivered to tissues. Muscles without oxygen start to convert to anaerobic metabolism to get their ATP. The waste product of anaerobic metabolism is lactic acid. The buildup of lactic acid without the kidney 104 excreting it causes metabolic acidosis. Clinical Correlations January 12th, 2007, A 28 year-old mother of three from Sacramento decides to go on a radio program to compete in a contest called, “Hold your Wee for a Wii.” During this contest, contestants drank great volumes of plain water. She drank 6 liters in 2 hours (2 liters an hour). The maximum the kidney can filter is 1 liter an hour. After the contest, she called her co-workers to say she wasn’t coming to work because her head hurt so badly. Later she is found dead. 105 Clinical Correlations Drinking too much water changes the extracellular osmolality. When the plasma is too dilute (too much water, too few solutes), water will leave the bloodstream to enter the tissues, where there are more solutes (solutes SUCK!). Water will enter the tissues (intracellular body fluid compartment), including the brain. The excess water will cause the brain to swell. 106 Water moves through Compartments Intracellular water (or other fluid) is the watery substance inside a cell. Interstitial water (or other fluid) is the watery substance between cells. Extracellular water (or other fluid) is the watery substance that is outside of cells. Some of it may be interstitial, some may be in the blood, joints, CSF, etc. The concentration of individual solutes (glucose, sodium, potassium, chloride) is different in intracellular fluid than it is in extracellular or interstitial fluid, but the total osmolarity (concentration of all the solutes combined) of the intracellular fluid, extracellular fluid, and interstitial and is the same. Water can move from one compartment to another. It can be drawn out of the plasma to enter the interstitial compartment first, and then it may enter the cells. Water can also move from the cells to the interstitial compartment, then into the bloodstream. 107 Water/Salt Imbalance Problems Expansion: the body has retained too much water Contraction: the body has too little water Hypo-osmotic volume Hyperosmotic volume The water in the body has too much water, too few solutes The water in the body has too little water, too many solutes Isosmotic volume The water in the body has the proper balance of water and solutes. 108 Water/Salt Imbalance Problems Hypo-osmotic volume expansion Excessive water drinking; plasma osmolality is reduced from too much water, not enough solutes (hypo-osmotic) and the extracellular fluid (outside of cells) volume has increased (expansion). Hypo-osmotic volume contraction Excessive sweating; the person has lost a lot of salt, but has lost some water, too. They are dehydrated (contraction) and have low salt levels (hypo-osmotic). The water in the body has low osmolality due to loss of the salt. Hyperosmotic volume expansion High salt intake; there is too many solutes, water is retained, so the overall volume is increased (expansion), but there is a lot of salt, so osmolality is increased (hyperosmotic). Hyperosmotic volume contraction Dehydration; the person has lost a lot of water, so overall volume is decreased (contraction). The salt level has not changed, so that means 109 more salt dissolved in less water (hyperosmotic). Water/Salt Imbalance Problems Isosmotic Volume Contraction Diarrhea; loss of water and solutes. Overall water/salt balance is maintained (isosmotic), but person loses overall volume (contraction). Isosmotic Volume Expansion Salt Infusion; person receives an i.v. of normal saline (isosmotic), and overall volume of body fluid increases (expansion). 110 Hyperosmotic volume contraction There would be elevated protein concentration but NO CHANGE in hematocrit with this condition Diabetes insipidus would cause this condition 111 Hyperosmotic volume expansion Conn’s disease would cause this condition There would be decreased protein concentration and hematocrit 112 Hypo-osmotic volume contraction Addison’s Disease would cause this condition There would be increased protein concentration and hematocrit 113 Hypo-osmotic volume expansion Syndrome of inappropriate ADH would cause this condition There would be decreased protein concentration but NO CHANGE in hematocrit with this 114 Iso-osmotic volume expansion There would be decreased protein concentration and hematocrit Infusion of a 0.9g% saline solution would cause this condition In these conditions there would be NO CHANGE in the intracellular volume nor osmolality 115 Iso-osmotic volume contraction In these conditions there would be NO CHANGE in the intracellular volume nor osmolality There would be increased protein concentration and hematocrit Diarrhea or burns would cause this condition 116 Water Imbalance category Condition Disorder Proteins Hct Drinking too much water Low Normal or inappropriate ADH Syndrome Hypo-osmotic volume expansion Excess water, low solutes Hypo-osmotic volume contraction Loss of water and salt Addison's disease High High Hyperosmotic volume expansion High salt intake Conn's disease Low Low Hyperosmotic volume contraction Loss of water, normal salt levels Diabetes insipidis High Normal Isosmotic volume expansion Increase in normal saline Normal saline iv Low Low Isosmotic volume contraction Loss of water and solutes, but water/salt is normal Diarrhea High High 117 Hyponatremia (too little sodium in the blood) Causes excessive sweating persistent diarrhea overuse of diuretic drugs 118 Hypokalemia (low potassium in the blood) Causes Inadequate potassium intake (rare) Gastrointestinal loss (vomiting or diarrhea) Urinary loss Thiazide diuretics Alkalosis in the blood Disease states that cause high aldosterone levels Conn’s syndrome (hyperaldosteronism) Cushing's syndrome (excess cortisol binds to the Na+/K+ pumps, so it acts like aldosterone). 119 Clinical Correlations Addison’s Disease Conn’s Disease Diabetes Mellitus Diabetes Insipidus Cushing’s Disease Know which of these diseases has hypernatremia, hypokalemia, hypo or hyperglycemia, etc. 120 Addison’s Disease Chronic adrenal insufficiency (low cortisol levels) Hyponatremia Hypoglycemia Hyperkalemia Possible death at times of extreme stress Addisonian crisis: low blood pressure coma 121 Conn’s Disease This is hyperaldosteronism. The person releases too much aldosterone, which increases sodium retention, so water follows, and hypertension results. Condition associated primarily with hypertension and mild hypernatremia and mild hypokalemia. No diabetogenic (glucose) problems. 122 Diabetes Mellitus Condition characterized by polyuria, glucosuria, polydipsia and ketonuria. Polyuria (frequent urination) Glucosuria (glucose in urine) Polydipsia (thirsty) Ketonuria (ketones in the urine) When insulin does not pull glucose into the body cells, it stays in high levels in the blood (hyperglycemia) and spills out in the urine (glucosuria). The body is starving, so it breaks down fat into fatty acids for energy, and ketones are the waste product. In small amounts, they are broken down in the liver, but in large amounts, they build up in the blood (ketoacidosis: lowers blood pH) and spill out into the urine (ketonuria). Starvation, fasting, prolonged vomiting, high protein diets, and low carbohydrate diets also cause this condition. 123 Diabetes Insipidus Condition characterized by polyuria and polydipsia, but not glucosuria. This is more like a disease of water loss (ADH is not produced). 124 Cushing’s Disease Hypernatremia Caused by lack of water in the blood, like dehydration. Hypokalemia (low potassium) Hyperglycemia (excess glucose) Diabetes mellitus Weight gain, particularly of the trunk and face with sparing of the limbs (central obesity), moon face, buffalo hump, and sometimes growth of facial hair. 125 K+ Na+ Glucose Addison's High Low Low Conn's Mild low Mild high Normal Diabetes Mellitus High Low High Diabetes Insipidus High High High Cushing's Low High High BP Low High Other Possible death at times of extreme stress Polyuria, glucosuria, polydipsia, ketonuria, ketoacidosis Polyuria, polydipsia only Diabetes (Polyuria, glucosuria, polydipsia, ketonuria), central obesity, moon face, buffalo hump, facial hair in women 126 Renal Physiology PART THREE Renal Acid-Base Balance 127 Acids are being created constantly through metabolism • Anaerobic respiration of glucose produces lactic acid • Fat metabolism yields organic acids and ketone bodies • Carbon dioxide is also an acid. Excess acids and bases must be eliminated from the body gas H2O + CO2 Lungs eliminate carbon dioxide aqueous H2CO3 H+ + HCO3 Kidneys can remove excess non-gas acids and bases Excessive Acids and Bases can cause pH changes---denature proteins • Normal pH of body fluids is 7.40 • Alkalosis (alkalemia) – arterial blood pH rises above 7.45 • Acidosis (acidemia) – arterial pH drops below 7.35 • Acidosis: – too much acid – Too little base • Alkalosis – Too much base – Too little acid Compensation for deviation • Lungs (only if not a respiratory problem) – If too much acid (low pH)—respiratory system will ventilate more (remove CO2) and this will raise pH back toward set point – If too little acid (high pH)—respiratory will ventilate less (trap CO2 in body) and this will lower pH back toward set point • Kidneys – If too much acid (low pH)—intercalated cells will secrete more acid into tubular lumen and make NEW bicarbonate (more base) and raise pH back to set point. – If too little acid/excessive base (high pH)proximal convoluted cells will NOT reabsorb filtered bicarbonate (base) and will eliminate it from the body to lower pH back toward normal. Acid-Base Balance How would your ventilation change if you had excessive acid? You would hyperventilate How would your ventilation change if you had excessive alkalosis? Your breathing would become shallow How can the kidneys control acids and bases? Bicarbonate is filtered and enters nephron at Bowman’s capsule Proximal convoluted tubule Can reabsorb all bicarbonate (say, when you need it to neutralize excessive acids in body) OR Can reabsorb some or NONE of the bicarbonate (maybe you have too much base in body and it needs to be eliminated) How can the kidneys control acids and bases? Acidosis Intercalated cells Secrete excessive hydrogen Secreted hydrogen binds to buffers in the lumen (ammonia and phosphate bases) Secretion of hydrogen leads to formation of bicarbonate HPO4NH3 What would happen if the respiratory system had a problem with ventilation? Respiratory Acidosis and Alkalosis Normal PCO2 fluctuates between 35 and 45 mmHg • Respiratory Acidosis (elevated CO2 greater than 45mmHg) • Depression of respiratory centers via narcotic, drugs, anesthetics • CNS disease and depression, trauma (brain damage) • Interference with respiratory muscles by disease, drugs, toxins • Restrictive, obstructive lung disease (pneumonia, emphysema) • Respiratory Alkalosis (less than 35mmHg- lowered CO2) • Hyperventilation syndrome/ psychological (fear, pain) • Overventilation on mechanical respirator • Ascent to high altitudes • Fever What if your metabolism changed? • Metabolic acidosis • Bicarbonate levels below normal (22 mEq/L) • Ingestion, infusion or production of more acids (alcohol) • Salicylate overdose (aspirin) • Diarrhea (loss of intestinal bicarbonate) • Accumulation of lactic acid in severe Diabetic ketoacidosis • starvation • • Metabolic alkalosis bicarbonate ion levels higher (greater than 26mEq/L) • Excessive loss of acids due to ingestion, infusion, or renal reabsorption of bases • Loss of gastric juice during vomiting • Intake of stomach antacids • Diuretic abuse (loss of H+ ions) • Severe potassium depletion • Steroid therapy Compensation If the kidneys are the problem, the respiratory system can compensate. If the kidneys are secreting too much H+(which makes too much bicarbonate, causing metabolic alkalosis), breathing will become slower so that less CO2 (an acid) is lost. If the kidneys are reabsorbing too much H+(metabolic acidosis), breathing will become faster. Compensation If the respiratory system is the problem, the kidneys can compensate. If breathing is too rapid (too much CO2, an acid, is lost, leaving the blood in respiratory alkalosis), Kidneys respond by reabsorbing more H+. If breathing is too shallow (not enough CO2 is lost, leaving the blood in respiratory acidosis), Kidneys respond by secreting more H+. Summary Let’s summarize so we can apply this to clinical conditions! Acidosis Can be metabolic or respiratory Alkalosis • Can be metabolic or respiratory Acidosis Acidosis is excessive blood acidity caused by an overabundance of acid in the blood or a loss of bicarbonate from the blood (metabolic acidosis), or by a buildup of carbon dioxide in the blood that results from poor lung function or slow breathing (respiratory acidosis). Acidosis Blood acidity increases when people ingest substances that contain or produce acid or when the lungs do not expel enough carbon dioxide. People with metabolic acidosis have nausea, vomiting, and fatigue and may breathe faster and deeper than normal. People with respiratory acidosis have headache and confusion, and breathing may appear shallow, slow or both. Tests on blood samples show there is too much acid. Doctors treat the cause of the acidosis. Metabolic acidosis Caused from a decrease in bicarbonate in the blood because of ingestion of an acid (aspirin, ethanol, or antifreeze) or too many acidic waste products have built up (such as from untreated diabetes mellitus or eating too much protein that the kidneys cannot keep up with excreting the acid ), or it could be from loss of bicarbonate from diarrhea. Treatment is give i.v. of sodium bicarbonate. Respiratory acidosis Caused from an increase in CO2 in the blood because the lungs are hypoventilating (seen in asthma, COPD, and overuse of sedatives or narcotics such as valium, heroin, or other drugs which make you sleepy). Treatment is to increase ventilation (oxygen mask). Respiratory acidosis May have no symptoms but usually experience headache, nausea, vomiting, and fatigue. Breathing becomes deeper and slightly faster (as the body tries to correct the acidosis by expelling more carbon dioxide). As the acidosis worsens, people begin to feel extremely weak and drowsy and may feel confused and increasingly nauseated. Eventually, blood pressure can fall, leading to shock, coma, and death. Alkalosis Alkalosis is excessive blood alkalinity caused by an overabundance of bicarbonate in the blood or a loss of acid from the blood (metabolic alkalosis), or by a low level of carbon dioxide in the blood that results from rapid or deep breathing (respiratory alkalosis). Alkalosis People may have irritability, muscle twitching, or muscle cramps, or even muscle spasms. Blood is tested to diagnose alkalosis. Metabolic alkalosis is treated by replacing water and electrolytes. Respiratory alkalosis is treated by slowing breathing. Metabolic alkalosis Caused from an increase in bicarbonate in the blood because of ingestion of excess antacid (Tums), eating excess fruits (vegetarian diets and fad diets*), loss of acid from vomiting, or loss of potassium from diuretics. Treatment is to give an anti-emetic if the problem is from vomiting. If not, give an i.v. of normal saline to increase the blood volume. If potassium is also low, would have to add that to the i.v. Respiratory alkalosis Caused from a decrease in CO2 in the blood because the lungs are hyperventilating (anxiety, but not panting). Treatment is to breathe into a paper bag for a while. Condition pH Resp CO2 Bicarb Compensating? Resp acidosis Low Hypoventilating High High Yes Resp acidosis Low Hypoventilating High Low No Resp alkalosis High Hyperventilating Low Low Yes Resp alkalosis High Hyperventilating Low High No Metab acidosis Low Normal Low Low Yes Metab acidosis Low Normal High Low No Metab Alkalosis High Normal High high Yes Metab Alkalosis High Normal Low High No