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PHYSIOLOGY 2 LECTURE (5) MONDAY 4-7-2016 How the kidneys handle sodium Na+ ? At the same compartment : cations = anions [ the composition must be electrons neutral ] Average Na+ intake in the body per day = around 155 mmole /day = 5gm - the kidneys removed 150→ the left 5 removed by other secretions ( sweating , fesses) Average Na+ output (execration) in the body should be the same = 155mmol/day Balanced Na+ : Na+ intake = Na+ output - Positive balanced : Na+ intake > Na+ output more Na+ intake - Negative balanced : Na+ intake < Na+ output more Na+ output - Kidneys major organ in regulating Na+ homeostasis (balanced)→ Mainly (not only) Na+ homeostasis achieve by the kidneys Na+ is important because it determine the osmolarity of plasma , for example (ECF) - The osmolarity : amount 300 ml osmol/ L of (ECF) ,(ISF) , (ICF) → Na+ 300 ml osmol /L - Na+ Major cation in ECF responsible about ½ osmolarity o Na+ determine the osmolarity ? you can predict the osmolarity by known the conc. Of ion o Osmolarity of Na+ = conc. Of Na+ , * 2.1 … 140 * 2.1 = 294 - Osmolarity is the same in 3 compartment : 1- Blood (plasma ) : the composition of plasma is very similar “not identical , not copy base , not mirror image ) of ( ISF) 2- ICF : Totally different for example → a) Na+ inside = 14 ,, outside = 140 b) protein not the same 6-8 gm //// 1-2 → depending on (ISF) - One exception is the osmolarity : determine by amount of water , water moves freely in these 3 compartments , make the osmolarity the same [Osmolarity the same between 3 compartments] - When all body fluids have an osmolarity near 300 mOsm/L, the osmotic pressure of the two fluid compartments are equal = no net water movement occurs. This is called iso-osmotic or isotonic. Osmolarity & osmolality : الدكتور ما شرحه بس إحنا الزم نعرفه " “ سؤال امتحان The measurements are expressed as: o Osmoles and milliosmoles – to describe the solute particles contained in a solution Nermeen Al Bkerat physiology (2) lecture 5 Monday 4-7-2016 Osmolarity : is the number of milliosmoles/liter (mOsm/L) of solution. It is the concentration of an osmotic solution. This is the common bedside calculation used in clinical settings for osmotic activity. Osmolarity is the measure of solute concentration per unit VOLUME of solvent,, It’s not the same as tonicity! Osmolarity takes into account ALL of the solute concentrations, not just the ones that cant cross the semi permeable membrane. o Example: Plasma and other body fluid osmolarity: 270 – 300 mOsm/L Osmolality is the number of milliosmoles/ kg (mOsm/kg ) of solvent. It is the concentration of the particles that is dissolved in a fluid. This is the clinical laboratory measurement using an osmometer. Osmolality is the measure of solute concentration per unit MASS of solvent ,,You never measure osmolarity in practice, because water changes its volume according to temperature (but mass remains the same, and so it is more convenient and consistent) o o o o Example: Urine osmolality: extreme range of 50 – 1400 mOsm/kg water, but average is about 500 – 800 mOsm. After an overnight fast, the urine osmolality should be at least 3 times the serum osmolality. Example: Serum osmolality: 282 – 295 mOsm/kg water Osmolality is the same in the ICF and the ECF. Both inside and outside, the osmolality is 285-290 mOsm/K OSMOLALITY VERSUS OSMOLARITY Osmolarity is affected by changes in water content, as well as temperature and pressure. In contrast, osmolality is independent of temperature and pressure. For a given solution, osmolarity is slightly less than osmolality, because the total solvent weight (the divisor used for osmolality) excludes the weight of any solutes, whereas the total solution volume (used for osmolarity) includes solute content. Otherwise, one litre of plasma would be equivalent to one kilogram of plasma, and plasma osmolarity and plasma osmolality would be equal. However, at low concentrations (below about 500 mM), the mass of the solute is negligible compared to the mass of the solvent, and osmolarity and osmolality are very similar Na+ always followed by water : You have more Na+ → cell expansion ~ you have less Na+ → cell shrink Explanation : فقط للتوضيح Nermeen Al Bkerat physiology (2) lecture 5 Monday 4-7-2016 - Hypotonic solutions will move water into the cell, causing the cell to swell and potential burst. By lowering the serum osmolarity, the body fluids shift out of the blood vessels into the interstitial tissue and cells. Hypotonic solutions hydrate the cells and can deplete the circulatory system. - Hypertonic solutions conversely cause the water from within a cell to move to the ECF compartment, causing the cell to shrink. These solutions are used to replace electrolytes. Hypertonic dextrose solutions when used alone, shifts ECF from interstitial to plasma. EXCHANDES OF Na : Na+ is exchanged with hydrogen → counter transport (anti transport) : a) When Na+ [high to low] interred is reabsorb , b) hydrogen [low to high] out is secreted c) If you have kidneys problem you may not able to conserve or to execrate Na+ Glucose with Na → co-transport (secondary active transport) a) Na+ [high to low] inter b) with GLU inter [low to high ] Ca+2 with Na+ → counter transport a) Ca+2 leave the cell from low to high conc. Through counter transport secondary active transport + Na has relationship with : 1) EC volume , blood pressure , hypertension [ you should not eat Na+Cl- salt ] 2) Action potential , excitability , depolarization 3) Reabsorption (GLU, amino acid) & secretion ( H+ , K+ ) inside the kidney Filtered load of Na+ : ضروري فهم طريقة الحل,, بس أليون مختلف,, سؤال امتحان - FILTERED LOAD : how much Na+ is filtered in the bowman`s space per unit time - GFR =125 ml/min → *60*24 = 180 L/day → each Liter of GFR contain 140 mlEq/L … how much Na+ filtered per day ? (filtered load of Na+ ) 180 * 140 = 25200 mlEq/day - 25200 inter tubules →→ 150 out ( urine form ) SO (25200-150 = 2550 ) is being reabsorbed Reabsorption = 99.4 % (Na+) execration = 0.6 % ,, if we double : 0.6 % *2 = 1.2 double the amount of execrated water DIURETICS : Na+ followed by water … DIURETICS : function based on decrease Na+ Reabsorption in the kidneys Diuretics types : 1- strong diuretic : inhibit Reabsorption of Na more {ex: Lasix } Nermeen Al Bkerat physiology (2) lecture 5 Monday 4-7-2016 2- intermediate diuretic : inhibit Reabsorption of Na medium { ex : thiazide } 3- weak diuretic : inhibit Reabsorption of Na less { ex : aldosterone antagonist } Na+ side action (target) of diuretics Almost filtered Na+ being reabsorbed ,, small part (not reabsorbed) execrated in urine Where Na+ is reabsorbed ??? in the kidneys (Nephron) 1) 65% in a proximal tubules [ The rest 35% ] 2) 25% in ascending limb of loop of henle - Diuretics work here : Lasix - properties of Lasix diuretic : a) side action of the loop b) GENERIC NAME(S) : FUROSEMIDE c) Strong diuretic –because it has a chance to work up to 25% of Na+ → it inhibit Na+ Reabsorption 3) Nothing in descending limb of loop of henle → because it’s not permeable for Na+ & permeable for water 4) 10% In early distal tubules (the late ascending) - Diuretics work here : Hydrochlorothiazide - properties of Hydrochlorothiazide : a. intermediate in strength b. has a chance to work up to 10% 5) 4.5% in collecting duct : - Diuretics work here : aldosterone antagonist - Antagonism of these receptors inhibits sodium resorption in the collecting duct of the Nephron in the kidneys. This interferes with sodium/potassium exchange, reducing urinary potassium excretion and weakly increasing water excretion (diuresis). - to prevent the hormone aldosterone from the binding with the receptors own and compete with him on the receptors on the cells so limit its effect - Aldosterone antagonist keep reabs. Of Na but there is no secretion for K )K SPARING DIURETICS week( summary : 65 % proximal ,, 0% descending ,, 25% ascending , 10% distal tubules , 4.5% collecting duct ,, 0.5% excretion Most important segment in Nephron in Na+ homeostasis ? distal tubules because Na+ Reabsorption under effect of aldosterone secreted from adrenal cortex then goes to kidneys → make 2 thing : 1) Reabsorption of Na+ 2) excretion of K Nermeen Al Bkerat physiology (2) lecture 5 Monday 4-7-2016 hyperaldosteronism : The symptoms include high blood pressure, low blood levels of potassium, an abnormal increase in blood volume Primary hyperaldosteronism (Conn's syndrome or aldosterone-producing adrenal tumor) More water ,, more Na Reabsorption (hypertension ) , hypervolemia Too much lost of K (hypokalemia) The principle cells : in the distal tubules reabsorb Na+ in exchange for K+ then secreted K+ in the lumen & reuptake Luminal side : K = 4 ,,, Na = 140 ,,, Ca = 10-3 = 1 mlmol Inside cell : K = 150 , ,,, Na = 14 ,,,, Ca = 10-8 = 10 nanomol Principle cell : reabsorb Na & secrete K تمتص الصوديوم وتحط بداله بوتاسيوم To secret K more you need to remove K from luminal (push it out ) , you keep it ready for secretion Diuretics inhibit Na Reabsorption ,, water reaching distal tubules more ,,, increase flow of tubular fluid of distal tubules ,,, increase washing out of K - Cell keep secreted K = end up to hypokalemia - Diuretics Lasix or thiazide : الزم إلي بوخدوهم كل فترة نفحص عندهم البوتاسيوم ألنه ال hypokalemia خطرة و ممكن يأكلوا موز مثال أو حمضيات لتجنبها وازا ما زبط بوخدوا دواء لرفع مستوى البوتاسيوم - What is the mechanism responsible in hypokalemia when using diuretics ? decrease Na reabs. → Increase water flow in distal tubules → increase washing out of K FROM BLOOD TO urine K homeostasis : - intake = output = 100 mlEq/day - Kidneys remove 95 major organ in homeostasis ... left 5 other secretion - K in blood= 4 mlEq/L - K filtered load per day = k filtered in bowman`s space per day → 180 *4 = 720 . Why K homeostasis is imp ? i. depolarization –action potential ii. hyperkalemia (RMP)Resting membrane potential : membrane potential in cell at rest - Which ions determine RMP ? K - Equilibrium : net movement of K =0 , enter of K = out - K channel open at rest K moves freely Nermeen Al Bkerat physiology (2) lecture 5 Monday 4-7-2016 - -61*log(k inside the cell /k outside the cell) , = -90 mlvolt If Out increase >>> -75 mlvolt less more negative ,,,, has vary serous consequeneing in excitability of the cardiac cell o Cardiac cell become non excitable o Hyperkalimia produce sever cardiac diseases عدم انتظام دقات القلب K in urine comes from 2 sources : 1) filtrated no reabsorbed , 2) secreted (no Na secreted) - Eating too much K , most of K in urine , comes from secretion - Kidneys failure KF : result in hyperkalimia because there is no K secretion - KF : hyperkalimia , hypertension , acidosis no H secretion , anemia no erythropoietin , ECF expansion hypervolemia Nermeen Al Bkerat physiology (2) lecture 5 Monday 4-7-2016