Renal Part 2: Fluid and Electrolytes, Acid/Base Balance PDF

Renal Part 2: Fluid and Electrolytes, Acid/Base Balance 1. Glomerular Filtra=on Rate (GFR) Passive process / hydrosta1c pressure of forcing fluids and solutes through a membrane (3 layers-fenestrated capillary endothelium, basement membrane, foot processes of podocytes) Outward pressure – hydrosta1c...

Renal Part 2: Fluid and Electrolytes, Acid/Base Balance 1. Glomerular Filtra=on Rate (GFR) Passive process / hydrosta1c pressure of forcing fluids and solutes through a membrane (3 layers-fenestrated capillary endothelium, basement membrane, foot processes of podocytes) Outward pressure – hydrosta1c glomerular capillaries (HPgc) Inward pressure – hydrosta1c capsular space (HPcs) – Colloid osmo1c glomerular capillaries (OPgc) Net Filtra1on Pressure (NFP) = Outward pressures – Inward Pressures= HPgc – (HPcs + OPgc) How much? Factors affec1ng rate: NFP, glomerular surface area, membrane permeability About 180 L / day Normal GFR is 120-125 ml/min. How does it happen? All control mechanisms work only to change the GFRIntrinsic Controls: (within the kidney) called renal autoregula1on keep arterial pressure between 80 – 180 mmHg Myogenic mechanism – Increasing BP = vascular smooth muscle stretches and constricts afferent arterioles to restrict blood flow to the glomerulus or declining BP = vascular smooth muscle relaxes and dilates afferent arterioles to increase blood flow to the glomerulus Tubuloglomerular feedback mechanism • • • • • Directed by macula densa cells of the juxtaglomerular complex Located in walls of ascending limb of loop Respond to filtrate NaCl concentra1on Increased NaCl in filtrate = release of vasoconstrictors, constric1on of afferent arteriole, reduced flow to glomerulus Decreased NaCl in filtrate = inhibits vasoconstrictor release, increasing flow to glomerulus Extrinsic Controls: by the nervous and endocrine systems to maintain system blood pressure Sympathe=c nervous system • • • • Not engaged when ECF is normal volume If ECF is low blood is sent to vital organs/brain and the kidneys could be damaged SNY releases norepinephrine and smooth muscles constrict and so do afferent arterioles Decrease in GFR to restore BP Renin-Angiotensin-Aldosterone mechanism • • Main mechanism to increase BP Decreased BP causes release of Renin from granular cells of juxtaglomerular complex because o B1 adrenergic cells are ac1vated by baroreceptors o Macula densa cells are ac1vated by low NaCl concentra1on o Granular cell mechanoreceptors are less stretched Determinants of who gets filtered and who doesn’t • • • - total plasma volume filtered every 22 min most tubule contents return to blood in a transepithelial process beginning in proximal tubules either a transcellular or paracellular route o Transcellular route – apical membrane, cystol, tubule cell basolateral membrane, peritubular capillary endothelium o Paracellular route – between tubule cells, limited by 1ght junc1ons, in the proximal nephron the junc1ons leak out Ca,Mg, K, Na, H20 Glucose and amino acids are completely reabsorbed Water and ions are con1nuously regulated Ac1ve reabsorp1on requires ATP Passive reabsorp1on uses diffusion and osmosis 2. Regula=on mechanisms of GFR Myogenic – reflects property of vascular smooth muscle – contract when stretched, relaxes when not stretched, raising systema1c blood pressure stretches vascular smooth muscle is arteriolar walls causing the afferent arterioles to constrict this allows restric1on of blood floe into the glomerulus and prevents glomerular blood pressure from raising to damaging levels. Decreasing systema1c blood pressure causes dila1on of the afferent arterioles and raises glomerular hydrosta1c pressure Autoregula=on – adjus1ng its own resistance toe blood flow, the kidneys can maintain a nearly constant GFR despite fluctua1ons in systema1c arterial blood pressure, uses myogenic and tubuloglomerular feedback to do it. Neural – when extracellular fluid volume is extremely low neural controls over take autoregula1on. When BP falls norepinephrine is released by sympathe1c nerve fibers causing vascular smooth muscle to constrict, increasing peripheral resistance and increasing BP, this is a baroreceptor reflex. Constric1on of the arterioles decreases GFR. Hormonal – Renin-Angiotensin- Aldosterone mechanism, main mechanism for increasing BP. Low BP causes granular cells of juxtaglomerular complex to release renin and s1mulate • • • Sympathe1c nervous system – part of the baroreceptor reflex, renal sympathe1c nerves ac1vate beta 1 adrenergic receptors that release renin Ac1vated macula densa cells – low BP reduces GFR, when macula densa cells sense the low NaCl concentra1on of the slow GFR, they signal granular cells to release renin Reduced stretch –granular cells act as mechanoreceptors, a drop in arterial BP reduces tension in cells plasma membrane and s1mulates them to release renin 3. Tubules I – if you were a water molecule how would you be handled by the tubules include osmo=c forces, counter current exchanger, ADH • Movement of Na creates a strong osmo1c gradient • Water moves into the peritubular capillaries through aquaporins to follow Na • In the proximal convoluted tubule (PCT) aquaporins are always in the membrane causing obligatory water reabsorp1on regardless of hydra1on level • In the collec1ng ducts aquaporins are only in place if osmolality alerts the hypothalamus to release or inhibit ADH which is responsible for inser1ng the aquaporins. This is faculta1ve water reabsorp1on • countercurrent refers to two segments of the same tube being adjacent to each other and separated by a hairpin turn • The countercurrent exchanger is the flow of blood through the ascending and descending por1ons of the vasa recta • The vasa recta receive blood from the afferent tubule, sends it out the vein. It is highly permeable to water and solutes 4. Tubules II – if you were a sodium ion how would you be handled by the tubules include ac=ve transport, counter current mul=plier, role of aldosterone in NA/K an=port • Na is most abundant ca1on in filtrate • Na is almost always transcellular and ac1ve (using ATP) • At the basolateral membrane Na is pumped into inters11al space by the Na-K ATPase • Then hydrosta1c pressure is low and osmo1c pressure high in the peritubular capillaries allowing water to sweep Na in • At the apical membrane ac=ve pumping of Na from the tubule cells creates electrochemical gradient that eases crossing the apical membrane • An1port means that Na and K pass each other in opposite direc1ons as K is pumped into the tubule cells and Na moves out. K then leaks out through channels. • Aldosterone is released by adrenal cortex in direct response to K concentra1on, aldosterone targets collec1ng ducts and distal end of DCT to retain Na and K channels and Na-K ATPase so licle Na leaves the body in urine 5. Tubules III – if you were a glucose molecule how would you be handled including transport maximum implica=ons • Glucose is reabsorbed by secondary ac1ve transport • Na moves down the concentra1on gradient and cotransports another solute such as glucose across basolateral membrane with it • Some glucose is moved across the basolateral membrane using transport proteins • There is a transport maximum when transport proteins are used • Transport maximum is measured in mg/min and reflects the number of transport proteins available in the renal tubules to move glucose • When transporters are saturated, the excess is excreted in urine eg. diabetes mellitus 6. Endocrine func=on of the kidneys – the role of renin and aldosterone, how their release is regulated Renin • Enzyme released by the kidneys that raises blood pressure by ini1a1ng the reninangiotensin-aldosterone mechanism • When BP or blood volume falls, granular cells of the juxtaglomerular complex in the kidneys are excited, these cells then release renin, which then takes off part of the plasma protein angiotensin triggering an enzyme cascade that forms angiotensin II which simulates the glomerulosa to release aldosterone Role of Aldosterone • • Hormone produced by the adrenal cortex that regulates Na+ reabsorp1on and K+ secre1on by the kidneys Release is triggered by low BP or blood volume which triggers the renin-angiotensinaldosterone mechanism in which the end product is the release of aldosterone 7. Acid-base balance: why is our pH 7.4, what is a buffer and what are the lungs and kidneys role for pH control Buffer • Chemical buffer is a system of one or more compounds that resist changes in pH when a strong acid or base is added • Bind to the H+ ions when the pH drops • Release H+ ions when pH rises • Three major buffer systems are o Bicarbonate – mixture of carbonic acid and sodium bicarbonate, only important ECF buffer, the buffering power of this system is directly related to the concentra1ons of the buffering substance o Phosphate – nearly iden1cal to bicarb buffering system but the components are dihydrogen phosphate and monohydrogen phosphate, very effec1ve buffer in urine and ICF o Protein – Lungs • H+ is produced by CO2 transport, raising H+ levels s1mulate the respiratory center to increase respira1on rate which cause more CO2 removed from the blood reducing the H+ concentra1on • When blood pH rises respiratory center depresses and respira1on rate decreases allowing CO2 to accumulate causing the pH concentra1on to increase and pH is returned to normal Kidneys • Kidneys regulate acid-base balance by adjus1ng the amount of bicarbonate in the blood by o Bicarb Reabsorp1on • Genera1ng New Bicarb Ions either via excre1on of buffered H+ or via NH4+ excre1on • Binding H+ to buffers in the filtrate minimizes the H+ concentra1on gradient allowing the proton pumps of the type A intercalated cells to secrete large numbers of H+ ions to prevent acidosis • Uses the ammonium ion produced by the glutamine metabolism in PCT cells to secrete H+ ions to prevent acidosis o Bicarb ion secre1on – when the body is in alkalosis intercalated type B cells in the collec1ng duct exhibit net HCO3- secre1on while reclaiming H+ to acidify the blood