BIO5004A 3 Regulation of Ion and Water Balance 2024 PDF

Human physiology BIO-5004A/ BIO-5104A Renal Physiology III: Regulatory mechanisms in the kidney Dr Tracey swingler  Human physiology BIO-5004A/ BIO-5104A Lecture content Renal Physiology III: Homeostatic Regulatory mechanisms in the kidney: Osmoregulation...

Human physiology BIO-5004A/ BIO-5104A Renal Physiology III: Regulatory mechanisms in the kidney Dr Tracey swingler  Human physiology BIO-5004A/ BIO-5104A Lecture content Renal Physiology III: Homeostatic Regulatory mechanisms in the kidney: Osmoregulation ⁻ Osmoreceptors and baroreceptors ⁻ Hormonal regulation of water and ion balance: ADH, Aldosterone Regulation of blood pH Dr Tracey Swingler  Human physiology BIO-5004A/ BIO-5104A Learning outcomes Understand the principles of osmoregulation Describe how fluid volume and solute concentration is monitored and regulated Understand how the renal system balances pH levels of the blood Dr Tracey swingler Homeostasis Homeostasis has survival value because it means an animal can adapt to a Endotherm changing environment. Negative feedback: Attempt to maintain a NORM, within set parameters Endotherm use negative feedback mechanisms to maintain a constant internal temperature  Nerves in skin detect heat  Send signals to the brain  Brains signals to skin/ muscles  Internal temperature maintained Body temp of reptiles fluctuate with the external Normal range temp 36.1 – 37.2o C Ectotherm Basic elements of any kind of regulatory circuit Set point 36.1 – 37.2o C Hypother Internal body temp Hyperthermia mia 4-10 mmol/L Hypoglycaemia Blood glucose Hyperglycaemia pH 7.35 and Alkalosis Blood pH 7.45 Acidosis Systolic< 120/ Diastolic < 80mmHg Hypotension Blood pressure Hypertension 50-60% Hypovolemia Fluid volume Hypervolemia 275 to 295 mOsm/kg Set point Hyponatremia Osmolarity Hypernatremia Parameter , osmolarity, fluid volume are all interconnected Set point 36.1 – 37.2o C Blood pressure is influenced by the Hypother Internal body temp Hyperthermia volume of blood in the circulatory mia 4-10 mmol/L system. When blood volume increases, Hypoglycaemia Blood glucose Hyperglycaemia blood pressure rises pH 7.35 and Osmolarity= concentration of solutes in Alkalosis Blood pH 7.45 Acidosis body fluids. Systolic< 120/ Diastolic < 80mmHg Hypotension Blood pressure Hypertension When osmolarity is high it can draw water 50-60% out of cells and into the bloodstream, Hypovolemia Fluid volume Hypervolemia The increasing body’svolume and BP. pH is tightly regulated by the 275 to 295 mOsm/kg kidneys and lungs. Important for function Hyponatremia Osmolarity Hypernatremia of enzymes/ proteins, which in turn can influence blood pressure The kidneys maintain pH by excreting H+ pH, blood pressure (BP), fluid and reabsorbing bicarbonate (HCO3-) from volume, and osmolarity are all interconnected in maintaining urine. the body’s homeostasis The kidneys are central to this regulation. Set point 36.1 – 37.2o C Hypother Internal body temp Hyperthermia mia 4-10 mmol/L Hypoglycaemia Blood glucose Hyperglycaemia pH 7.35 and Alkalosis Blood pH 7.45 Acidosis Systolic< 120/ Diastolic < 80mmHg Hypotension Blood pressure Hypertension 50-60% Hypovolemia Fluid volume Hypervolemia 275 to 295 mOsm/kg Hyponatremia Osmolarity Hypernatremia They respond to changes in blood pressure and osmolarity by adjusting the excretion pH, blood pressure (BP), fluid or reabsorption of water, sodium, and volume, and osmolarity are all other electrolytes. interconnected in maintaining the body’s homeostasis Hormones antidiuretic hormone (ADH)  Osmoregulation The process of maintaining salt and water balance (osmotic balance) across membranes within the body Osmoreceptors Baroreceptors ADH Renin-angiotensin-aldosterone system rol of ion/water transport: The receptors Detecting alterations of Na+ Sodium concentration cannot be directly sensed concentrations & water volume as there are no specific ‚sodium-sensing receptors Alterations in total body sodium manifest as changes in 1. Osmolality of extracellular fluids 2. Volume of fluids (affects blood pressure) Changes of ion concentations and fluid volumes are indirectly detected by:  Osmoreceptors detect osmolality changes Set point  Baroreceptors detect pressure changes (volume Parameter changes- information on blood pressure and fluid levels ol of ion/water transport: Osmoreceptors Osmoreceptors are specialized neurons located in the hypothalamus (a few also in macula densa) Sensitive (1% changes) to changes in osmolarity. The resting cell (isotonic environment) emits low nerve impulses Resting Hypotonic conditions environment In hypertonic environment, water leaves cell by osmosis via AQP4 Hypertonic stimulation provokes cell shrinking and increases nervous signals Triggers action potentials to release ADH Induces nerve signals Signals generated by osmoreceptors: ADH release Signals generated by chemoreceptors causes the secretion of ADH from connected hypothalamic nerve cells ADH/ Vasopressin- small peptide hormone (9 aa) ADH is produced and stored in the neurons, released directly into blood stream Regulates the reabsorption of water 1. Increases water permeability of DCT/ collecting duct cells (AQP) 2. Increases urea transporters in the collecting duct, Infundibulum increases medulla urea concentration Thus, increases water reabsorption Produces concentrated urine H/ vasopressin regulation resets Excess water = decreased osmolarity Sensor Osmoreceptors in hypothalamus sense osmolarity decrease ADH secr Decrease in ADH decrease aquoporins in collecting duct Reaction Decrease in water permeability, decrease water reabsorption Dehydrated= increased osmolarity Osmoreceptors in hypothalamus sense osmolarity increase ADH secr Increase in ADH increase aquoporins in collecting duct Increase in water permeability, increase water reabsorption rol of ion/water transport: Baroreceptors Mean arterial pressure is constantly monitored by baroreceptors (pressure sensors) within the circulatory system. Baroreceptors: specialized sensors (mechanoreceptor) located in the walls of blood vessels. Short term: Adjustments are made to cardiac output and resistance (ANS influence on the heart). (BAROREFLEX) Long term (days): control involves adjusting total blood volume by restoring normal salt and water balance through mechanisms that regulate urine output and thirst rol of ion/water transport: Baroreceptors High pressure baroreceptors Two types of baroreceptors: 1. High pressure arterial receptors- Aortic arch, carotid sinus- Prevent changes in blood pressure in the short term 2. Low pressure receptors (Volume receptors) - In the large veins of the heart atria and in the pulmonary vasculature Low pressure baroreceptors and also the juxtaglomerular cells of the kidney ⁻ Low pressure baroreceptors have both circulatory and renal effects ⁻ More long-term changes to BP related to changes in blood volume: - Changes in ADH secretion - Release of aldosterone ol of ion/water transport: baroreceptors High pressure baroreceptors Short term/ quick adjustments (over ~2 heart beats) ⁻ Stand up quickly- change in BP ⁻ HP Baroreceptors sense a lack of stretching of the artery walls ⁻ Signals sent to brain, which interprets this as inadequate blood flow ⁻ Signals sent to blood vessels to tighten up to raise brain stem blood pressure- short term adjustments Low pressure baroreceptors The renin–angiotensin–aldosterone system (RAAS) ⁻ Critical regulator of blood volume and systemic Aldosterone vascular resistance on a long-term basis. ⁻ The blood volume determines the mean pressure throughout the system -Angiotensin aldosterone system (RAAS) Osmoreceptors Baroreceptors / Main job of the cardiovascular system- keep blood baroreceptors moving Adrenal cortex To help facilitate this BP and blood volume kept under tight control This is done by Renin Angiotensin Aldosterone System ALDOSTERONE ⁻ STERIOD HORMONE ⁻ acts slower, as it induces changes in gene expression ⁻ Adrenal cortex produces Aldosterone ⁻ Stimulates Na+ reabsorption by the DCT and cortical collecting duct (Fine tuning as most Na reabsorbed) ⁻ Induces the synthesis of ion channels and pumps Water only Salt and water RAAS: Regulates blood pressure and water balance. Activated by a loss of blood volume or a drop in ivation of RAAS: Three signals 1. JG cells are supplied by the sympathetic nerve fibres ⁻ Baroreceptors (aortic arch/ carotid sinus) activate SNS ⁻ Stretched: fibres are down regulated ⁻ Collapse: detects low blood pressure, nerve fibres Juxtaglomerular cells activated ⁻ B1 Adrenergic receptors stimulate renin release Stretched: increased BP 2. Baroreceptors in JGA: juxtaglomerular cells Collapse: ⁻ Low pressured detected arteriole collapse stimulates decreased BP renin release 3. Macula densa cells (chemoreceptors) sense GFR based on solute concentration. ⁻ BP drops, RBF and GFR drop. ⁻ Macula densa cells release prostoglsndin (PGE2) ⁻ Juxtglomerular cells release renin -Angiotensin aldosterone system (RAAS) Renin- Released into the blood plasma Loss of blood volume or a drop in blood pressure. Angiotensinogen produced RENIN (enzyme) stored in macula densa cells by the liver, always present in blood RENIN  Hydrolyses angiotensinogen to ANGIOTENSIN I Endothelial cells in the lungs express on their ANGIOTENSIN-CONVERTING ENZYME surface ACE (ACE) cleaved two amino acids of ANGIOTENSIN I  ANGIOTENSIN Angio-tensin II blood, tensin- tense) ( angio- Angiotensinogen II cause smooth muscle cells to Angiotensinogen II contract, decreased RBF, decreased GFR causes vasoconstriction of afferent and efferent Angiotensin II also act on DCT, increased Na+ arterioles Reabsorption And Reabsorption of Na+ Angiotensin II also acts on the hypothalamus- Increases thirst and (ADH- DCT/ collecting duct AQP) -Angiotensin aldosterone system (RAAS) Angiotensin stimulates the adrenal cortex to secrete ALDOSTERONE ALDOSTERONE- STERIOD HORMONE (mineralocorticoid) ⁻ acts slower, as it induces changes in gene expression ⁻ Aldosterone bind to its intracellular receptor ⁻ Induces the synthesis of Na+- K+ ATPase ⁻ Stimulates DCT and cortical collecting duct to reabsorb Na+ (Fine tuning as most Na reabsorbed) ⁻ Na reabsorbed and water follows ⁻ Increases blood volume and BP Increased water and sodium reabsorption Key points  Blood pH, pressure, volume, osmolarity interconnected and regulated by the kidney  Osmoregulators: Monitor osmolarity (solute conc. of the blood) ADH released from posterior pituitary gland- AQP insertion, water reabsorption  Baroreceptors: Mechanoreceptors, monitor stretch RAAS responds to drop in BP- increasing Na+ and water reabsorption  The kidney and pH balance pH indicates the level of H+ ions H homeostasis Metabolism depends on the function of enzymes- sensitive to pH Most cells can only survive within a certain pH range Pure water contains equal amount of ions H+ = OH- Proteins such as enzymes are denatured and destroyed H2O  H+ + OH- Blood and tissue fluid normally have a pH of Hydrogen ionHydroxide ion 7.35- 7.45 Homeostatically regulated: pH is one of the most important aspects of homeostasis The body has several mechanisms in place to regulate blood pH More H+ = acidic More OH- = Base/ alkaline : Potential of hydrogen Saliva Intestine 6.5-7.5 7-8.5 Stomach Blood 1.5-6.5 7.35-7.45 pH is a scale that describes how acidic or basic a fluid is. pH is maintained by a complex system of feedback and regulation as the body's metabolic processes produces acids Cells produce H+ as byproducts: pH indicates the level Metabolic activities, Respiration, Dietary +of H+ ions H >OH - OH->H+ intake PH = − log Lactic acid from, Phosphoric acid, Fatty acids [H +] and ketones, Carbonic acid H Blood pH needs to be maintained within 7.35- + p 7.45 H The pH scale is logarithmic and is inversely proportional to the [H+] Difference of one pH unit is equivalent to a tenfold difference in [H+] ratory and renal systems play key roles in regulating …..but in different ways The respiratory system regulates pH by controlling the levels of carbon dioxide (CO₂) in the blood. CO₂ combines with water to form carbonic acid, which dissociates into hydrogen ions (H⁺) and bicarbonate ions (HCO₃⁻) Blood pH adjusted in minutes The kidneys regulate blood pH by reabsorbing filtered HCO3- excreting H+ produced from metabolism Long term balance of H+ term regulation of pH by the kidneys 1. Reabsorption of Bicarbonate: Bicarbonate is freely filtered across the HCO3- glomerulus The kidneys reabsorb bicarbonate ions from the H+ urine back into the bloodstream. This process helps to neutralize excess acids in the blood, maintaining a stable pH level Depending on whether the body is in a 2. Secretion of Hydrogen Ions: state of acidosis or alkalosis, the The kidneys also secrete hydrogen ions into the kidneys adjust the amounts of urine. bicarbonate reabsorbed and hydrogen ions secreted. In acidosis, more By excreting these ions, the kidneys help to bicarbonate is reabsorbed, and more reduce the acidity of the blood hydrogen ions are secreted. In alkalosis, the opposite occurs 3. Ammoniagenesis: In response to acidosis (an excess of acid in the body), the kidneys generate ammonia (NH₃), which acts as a buffer. This process helps to neutralize the excess mal maintenance of blood pH: HCO3- ‘reabsorption’ Proximal convoluted tubule Tubule Lumen Epithelium Blood vessel HCO3- freely filtered across into the glomerulus Na+ A series of chemical reactions moves HCO3- back into the bloo Na + HCO + H+ + HCO3- 3 - H+ HCO3- HCO3- combines with H+ to form carbonic acid H2CO3 HCO3- H2CO3 Cl - Carbonic anhydrase converts to water and H+ , diffuse into ce + + CA CA type 4 type Water and H2O combine to form carbonic acid 2 H2O+ CO2 H2O+ CO2 Dissociates into H+ and bicarbonate Exchanged for Cl- or symported with Na+ Reabsorption……sort of! mal maintenance of blood pH: H+ secretion Tubule Lumen Epithelium Blood H+ ATPase pumps H+ into the tubule vessel The filtrate can only hold so much before pH drops ATP too low H+ H+ Ammoniagenesis Therefore, uses chemical buffer - NH3 NH4 Amino acids Cells breakdown amino acids into ammonia (lipid NH4 NH4 NH3 soluble), diffuses into the tubule NH4 + Combines with H+ to form ammonium ion NH4+ Cl - NH +Cl- 4 Combines with Cl- in the urine- Excreted Weakly Excreted acidic elps get rid of excess H+ term regulation of pH by the kidneys Overview Both H+ and HCO3- are freely filtered In the PCT and DCT, some hydrogen ions are H+HCO3- H+ HCO3- secreted into the tubular fluid from the blood, maintaining acid-base balance H+ H+ 1. H+ secreted into the tubule filtrate 2. Binds to HCO3-, ammonia, or phosphate 3. Bound or free H+ expelled from the body The kidneys neutralise more acid or base than the respiratory system of chemical buffers, long term Depending on whether the body is in a state of acidosis or alkalosis, the kidneys adjust the amounts of bicarbonate reabsorbed and hydrogen ions secreted. Key points  Respiratory system and kidney both regulate pH blood (short and longer term respectively) H+HCO3- H+ HCO3-  Bicarbonate is freely filtered and reabsorbed…(sort of) in the PCT H+ H+  H+ secreted into the DCT  Excess H+ buffer by ammoniagenesis (or phosphate) forming a weaker acid and excreted Any questions?