Dr. Chris Doumen Collin County Community College BIOL 2402 Fluid/Electrolyte Regulation 1 Body Water Content On average, we are 50-60 % water For a 70 kg male = 40 liters water This water is divided into intracellular water ( 28 L) extracellular water plasma ( 3 L) interstitial fluid ( 11 L) 2 1
Body Water Content Cell membrane 3 Body Water Content 4 2
Homeostasis and Cell Membranes Barrier between plasma and interstitial fluid are the walls of the smallest blood vessels that supply the cells. These capillaries are very permeable to fluids and smaller molecules but restrict passage of blood cells and proteins. Plasma and ICF tend to have similar composition with respect to ions and smaller molecules! ECF 5 Homeostasis and Cell Membranes Cell membrane provides a selective permeable barrier between ECF and ICF and thus functions as a gate keeper. It determines what goes in and out of the cell. Optimal functioning of a cell depends on optimal conditions of the environment that surrounds the cell, e.g., the ECF. The state of the ECF ( and of the plasma ) determines the state of the ICF 6 3
Electrolyte Distribution 7 Electrolyte Distribution Despite the differences in electrolytes, the osmotic concentration is very similar between ECF and ICF Equal osmotic concentration between ECF and ICF means no net change in water flow between the two compartments. Disequilibrium occurs when there is a change in osmotic concentration between ECF and ICF. Due to the semi-permeable nature of the cell membrane, this disequilibrium will manifest itself mainly by changes in concentration of electrolytes in the ECF. 8 4
Homeostasis Activities The state of the ECF ( and of the plasma ) determines the state of the ICF! Changes in ECF thus need to be compensated for by the body in order to prevent our cells from shrinking or exploding. Renal activities are crucial in this task of keeping the ECF in check. 9 Homeostasis Activities Control of the ECF is mainly a control of blood plasma. Our blood plasma ( and thus ECF) has an osmolarity of 285-300 mosm and healthy people have an amazing ability to maintain a rather constant osmolarity. This constant osmolarity is achieved by constantly adjusting the two main components of the ECF that influence osmolarity e.g. water itself the electrolytes that are dissolved in it. 10 5
Homeostasis Activities Stabilizing water volume, electrolyte balance and ph value of the ECF involves three inter-related processes. Control of the ECF is mainly a control of blood plasma. Fluid Balance is present when amount of water gain per day equals water loss fluid balance is mostly a digestive and urinary system process Electrolyte Balance because cells can t transport water, the ICF water content is regulated by regulation of electrolytes in and out of the cells. once again, electrolyte balance is mostly a function of digestive and urinary system. 11 Homeostasis Activities The last process is not a direct water and osmolarity stabilizing process, but protons have drastic effects on ph values and are regulated very tightly. Acid-Base Balance The body is in acid-base balance when the production of hydrogen ions is offset by their loss The primary problem for the body is a reduction in ph values since many daily metabolic processes generate protons The kidneys are responsible for proton elimination and bicarbonate retention. The lungs play an essential role in elimination of carbon dioxide. 12 6
Homeostasis Activities BASIC CONCEPTS OF REGULATION All homeostatic mechanisms respond to changes in ECF, not ICF Receptors don t monitor total fluid or total electrolyte balance, but do monitor plasma volume and osmolarity changes. Cells cannot transport water molecules by active transport; water moves by means of osmotic forces. Body content of water or electrolytes rises if intake exceeds outflow 13 Homeostasis Regulation PRIMARY HORMONES INVOLVED IN REGULATION Antidiuretic hormone (ADH) Stimulates water conservation and the thirst center Aldosterone Controls Na + absorption and K + loss along the DCT Natriuretic peptides (ANP and BNP) Reduce thirst and block the release of ADH and aldosterone 14 7
Fluid Balance Regulation 15 Fluid Balance Regulation 16 8
Fluid Balance Regulation The loss we experience daily is a combination of water AND electrolytes such as K +, Na +, Cl -, HPO 4 -, HCO 3 -. The function of the kidneys is to regulate the water and electrolyte balance. However, the kidneys cannot replenish the water lost or the electrolytes excreted by the body. This replenishment needs to come from the intake sources. Kidneys can only regulate the loss of water and electrolytes. 17 Fluid Balance Regulation 1. Thirst center Water Balance is achieved by 2 mechanisms Since the kidneys can only regulate the amount of water that is lost via the urinary system, the water loss via nonkidneys avenues makes fluid intake a necessary event in order to balance blood homeostasis When water is lost from our system, the Osmolarity of our blood tends to rise (makes things more concentrated) Osmoreceptor cells in hypothalamus dehydrate and depolarize Together with a dry mouth (less saliva production, it triggers the thirst sensation Conditions that result in an increase in osmolarity (Loss of lots of blood or eating salty food) make you thirsty. 18 9
Fluid Balance Regulation 19 Fluid Balance Regulation 2. ADH When Osmolarity rises, the hypothalamus is stimulated as well to release ADH ADH specifically works on the collecting ducts and inserts more water-channels This allows water to escape into the medulla area of the kidney as the collecting ducts move deeper along the osmotic gradient in the medulla. Release of ADH results in the kidneys excreting less urine, and more water redirected to blood 20 10
21 Fluid Balance Regulation Plasma ADH in function of Plasma Osmolarity 22 11
Fluid Balance Regulation (no ADH) +ADH 23 Fluid Balance Regulation ADH works via a camp mechanism and results in the insertion of water channels (aquaporins) in collecting ducts cells 24 12
Fluid Balance Regulation Result of water imbalances are overhydration or dehydration. Both conditions will cause changes in osmolarity of the body water compartments, and hence, osmosis. The resulting water movement between ECF and ICF is called fluid shifts! If ECF becomes hypertonic relative to ICF, water moves from ICF to ECF If ECF becomes hypotonic relative to ICF, mater moves from ECF into cells 25 Fluid Balance Regulation Because the ICF is twice as large as the ECF, it acts as a buffer zone for water and physiological changes in ECF water content will quickly be exchanged with ICF, resulting in minor changes in both compartments. ICF ECF Prolonged fluid shifts without corrections ( fluid or electrolyte intake for example) will result in pathological problems. 26 13
Electrolyte Balance Regulation Electrolytes are ions released through the dissociation of inorganic compounds. They are usually associated with salts! The balance of all the salts in our body is crucial for a wide array of activities Na +, K + for electrical activities of neurons, muscle Ca ++ for contractile activity, bone deposit Mg ++ for DNA replication, liberation of energy from ATP The kidneys are the organs that try to maintain that electrolyte balance. The food we take in is mostly adequate in salt content although some diets may be lacking in several 27 salts. Electrolyte Balance Regulation Two major ions are important that exert significant osmotic contribution and directly affect normal cellular function. They are Sodium Potassium Because sodium is most abundant in the ECF, sodium is the major player in electrolyte imbalances. Potassium imbalances are less common, but if they do occur, are significantly more dangerous! 28 14
Electrolyte Balance Regulation Central Role of Sodium Sodium salts make up 90% of all solutes in ECF Single most abundant cation in ECF (~142 meq/l) Exerts significant osmotic pressure Wherever sodium moves, water will follow by osmosis (water follows salts) Thus regulation of sodium is linked to BP, Blood volume and many other processes such as acid -base control How is sodium content regulated? 29 Sodium Regulation 1. Aldosterone Normally, 65 % of Na + is reabsorbed in PCT and another 25 % in loop of Henle The final 10 % of sodium re-absorption is determined by the presence of Aldosterone Action of aldosterone is to insert more Na-K pumps into the basolateral side of the Distal tubules. 30 15
Sodium Regulation If Aldosterone is high most all remaining Na + is reabsorbed as NaCl in DCT and Collecting tubules Water will follow when possible (depending on location) Urine volume decreases If Aldosterone is low No Na + is reclaimed and thus excreted Water will follow and excreted urine volume increases 31 Sodium Regulation How does Aldosterone work? 32 16
Sodium Regulation When membranes are permeable to water molecules, osmosis drives them to follow the movement of sodium ions pumped across membranes by the ion pumps. Water can also diffuse through adjacent tubule cells. Sodium pumping thus accomplishes water reabsorption. 33 Sodium Regulation What is the trigger for Aldosterone Release? Renin Results in the production of ANG II, which in turn triggers Aldosterone release from adrenal cortex JG cells release Renin due to : sympathetic nerve stimulation low blood pressure and blood volume (decreased stretch) decreased filtrate osmolarity that passes into the Distal convoluted Tubule low blood Na + levels 34 17
Sodium Regulation 35 Sodium Regulation 2. ADH Influence of ADH is an indirect effect on Na + balance : Increase in Na + (indicating dehydration) stimulates ADH directly by means of Hypothalamus osmoreceptors or by means of the Renin-angiotensin system (remember that Ang. II stimulates ADH release) Release of ADH is inhibited by low Na + ( which indicates too much fluid intake), allowing more water to be excreted in urine and re-establishing Na + osmolarity in blood 36 18
Sodium Regulation 37 Sodium Regulation 3. Other Factors Atrial Natriuretic peptide (ANP): produced by atria when blood pressure is high opposes ANG II effects by downregulating Renin production also inhibits ADH and aldosterone production promotes vasodilation and Na + and water loss by the kidneys (reduce BP) 38 19
Sodium Regulation 39 Sodium Regulation 40 20
Sodium Regulation Estrogens are similar to Aldosterone and thus enhance NaCl retention ( and thus water) explains water retention by woman during menstrual cycle when estrogens are high 41 Electrolyte Balance Regulation Regulation of Potassium K + is important in that too much or not enough potassium can lead to electrical malfunctioning with specific cardiac consequences and possibilities for sudden death. Similar to Na +, over 90 % of K + is reabsorbed in nephron tubules leaving some 10% to be excreted in the urine. 42 21
Potassium Balance Regulation In contrast to Na +, which is reabsorbed in the DCT and collecting tubules depending on need, K + balance is accomplished by changing the amount secreted into the urine filtrate (Na + is never secreted) Since K + is always secreted, situations may occur where K + is lost in the urine even in the face of a body deficiency 43 Potassium Balance Regulation Potassium is filtered from the glomerular capillaries. The relative rates of potassium reabsorption and secretion are determined by the law of mass action and by aldosterone, which increases sodium reabsorption at the expense of increased potassium secretion. Potassium balance is regulated by Concentration of K + Aldosterone Protons 44 22
Potassium Balance Regulation Mass action regulation of K If levels of K + increase in blood stream More K + diffuses into Interstitial fluid More K + transported into DCT via Na/K Pump Cells of the distal nephrons have a higher resting membrane potential at the lumen side ( -50 mv) The driving force for K + to leak out the cell is greater In addition, there is now a higher K + inside the DCT cells Lumen side has an abundance of K + leakage channels. Final result, more K + leaves (secreted) the cells into the lumen of the nephron via these leakage channels 45 Potassium Balance Regulation Mass action regulation of K -50 mv K + Peritubular capillary Why does K+ secretion not happen in PCT but mostly in distal parts of the nephron? 46 23
Potassium Balance Regulation Aldosterone the major control factor in regulation of K + High K + in blood triggers aldosterone release from adrenal glands directly Result is increase in Na-K pumps in the distal parts of the nephron. Also seems to incorporate more leakage channels for K + Effect is an increased K + secretion and an increased Na + reabsorption. 47 Potassium Balance Regulation Ingesting too much potassium stimulates aldosterone secretion from the adrenal cortex; aldosterone increases sodium reabsorption at the expense of increased potassium secretion. Also shown here is an indication that more potassium in the filtrate leads to greater potassium excretion in the urine. 48 24
Potassium Balance Regulation Regulation by Protons Whenever the ph of blood declines, the rate of potassium secretion declines This is due to the fact that hydrogen will compete with potassium, and thus hydrogen will be secreted in exchange for sodium instead of potassium in exchange for sodium Typical result is that people with acidosis may end up with hyperkalemia! 49 Potassium Balance Regulation Any factor that triggers aldosterone release can thus result in increased K + secretion Na + depletion ECF depletion drop in BP may result in K + depletion The Na-K pump in the distal parts of the nephron can also use H + instead of K +. Thus if there is an increased amount of blood H + ( acidosis), the excess H + will compete with K + and less K + gets to be secreted. 50 25