University of Jordan Faculty of Medicine Physiology || for Pharmacy L05 –Dr. Yanal Renal System Note: 1) Make sure you understand everything, exams questions will be based on understanding NOT memorizing alone 2) Anything between *** was not mentioned during the lecture (only for your knowledge) ----------------------------------------------------------------------------------------------------------3) Potassium K+ intake is100 mEq/day output must also be 100mEq/day for balance insurance. K+ balance when intake = output Potassium is removed from our body through kidney As we mentioned in the last lecture (L04): 4mEq/L in Plasma so in 180L/Day 4*180 = 720 mEq/day Filtered Load of K+ Let’s consider that urine should contain roughly 100mEq/day K+ Proximal Tubule 65% Descending limb of Henle (the nephron) 0% ascending limb of Henle 25% (impermeable to water) 100-65-0-25= 10% of Urine 10% of 720 is 72 mEq/day but the output is 100mEq/day so the extra 28mEq/day will be from Secretion Sources of K+ in Urine: 1) Filtration-Reabsorption = 72mEqlday 2) Secretion= 28mEq/day TOTAL =100 (in Urine (output)) Sources of Na+ in Urine: 1) Filtration-Reabsorption ONLY So if your K+ Intake was 200mEq/day instead of 100 mEq/day The extra 100 will be in the secretion (secretion will be 128 instead of 28mEq/day) Secretion is more important in K+ if your K+ intake increased Aldosterone from Adrenal cortex(gland) Reabsorption for Na+ & Secretion for K+ As we said in the previous lecture (L04) loop diuretics and thiazides (which are Aldosterone Antagonists) cause hypokalemia Note: adrenaline is secreted from the medulla 4) Phosphate in L04 5) Glucose Mwt of Glucose = 180 Freely Filtered Concentration of Glucose in GFR from 70-100 mg/dL Renal blood flow (RBF) is the volume of blood delivered to the kidneys per unit time. In humans, the kidneys together receive roughly 25% of cardiac Output which equals 1250 ml/min RBF = Plasma + Cells 650 of the RBF Plasma (Renal Plasma Flow) 20% of the Renal Plasma Flow will be filtered 125ml/min (GFR) 80% of the Renal Plasma Flow will continue through the efferent 535ml/min The Na+_Glucose co-transporter: Located in the apical membrane of the proximal tubule (on brush border), 2 Na+ and a molecule of glucose attach to the co-transporter Na+ goes from high low concentration Glucose goes from low high concentration Transporter (carrier) must be specific in kind and amount it has a saturation phenomenon (when it reaches plateau can’t carry any added molecules) Secondary active transport there is a saturation limit For glucose it has a filtered load that can be carried out in the proximal tubule to be reabsorbed in the blood NO glucose in the Urine (Normally all Glucose molecules are reabsorbed) NO glycosuria Glycosuria: the condition where Glucose appears in the Urine. Note: If Glucose escaped the proximal tubule, it cannot be reabsorbed anymore; because there is no Glucose transporter in the rest of the nephron Glucose will appear in the Urine Glycosuria After max saturation of Glucose in it’s transporters Glucose will start to appear in the Urine Glucose Normal concentration is 70-100 mg/dl (NO Glycosuria) when it reaches 180mg/dl (threshold for Glycosuria) it will start appearing in the urine. After threshold: Glucose in Plasma Glucose in Urine +1 +1 +2 +2 Q: How to distinguish Diabetes? When the fasting blood sugar is equal or more than 126mgldl So as a conclusion: 1) 70-100 mg/dl Normal 2) 100-125 mg/dl Pre-diabetic 3) Equal or more than 126 Diabetes Note: When post-prandial (after eating) blood sugar is 150mg/dl this is normal. Q: a patient have a fasting blood sugar = 140mg/dl, does he have Glucose in Urine? NOOOOO!! ONLY DIABETES In other cases, there might be a problem in the Glucose carrier itself For example the post-prandial blood sugar is 150mg/dl BUT there is Glucose in Urine!! This happens due to up normality in carriers Nephrogenic Glycosuria Nephrogenic Glycosuria: is a form of diabetes insipidus primarily due to pathology of the kidney Diabetogenic Glycosuria: due to lack of insulin 5) Amino Acids Average Mwt of Amino Acids = 110 we have large amino acids Phenylalanine Small amino acids Glycine So if we had a protein that it made of 400 amino acids then it’s Mwt = 110*400 = 44000 Which means it’s freely filtered 44000<70000 Q: where are amino acids reabsorbed? It is totally reabsorbed In the Proximal Tubule 100% (with Na+ via secondary active transport) Na+ goes from high low concentration Amino acids go from low high concentration There are many kinds of carriers for amino acids: 1) Neutral carriers 2) Acidic carries 3) Basic carriers 4) Cysteine carriers (if no carrier cystinuria: high concentration of the amino acid cysteine in the urine) And this will start stone formation (Cysteine stones) in the kidney حصى الكلى Note: there are many types of Kidney stones like: 1) Calcium stones 2) Struvite stones 3) Uric acid stones 4) Cysteine stones Q: what does the proximal tubular cell look like? Since the proximal tubule has many functions in the kidney it has brush border (to increase surface area) on the other side there is the Basolateral side Note: when we talked about sodium reabsorption we mentions that it occurs by secondary active transport (which does not require ATP) at the luminal side At the basolateral side any Na+ that enters the proximal tubule epithelial cell will leave it by the NaK pump (from low concentration to high concentration) which consumes ATP produced by the mitochondria at the basolateral side Remember when we mentioned that our body during normal metabolism makes acids not bases which means it has tendency for acidosis Some acids that are produced by metabolism: Sulfuric acid, phosphoric acid, lactic acid and CO2. When our body produces acids this will lead to too much H+ But our body will not tolerate acidosis because it will affect our enzymes activity Q: how my body will take care of the extra acids? By Bicarbonates H+ + HCO3- H2CO3 (carbonic acid) CO2 + H2O And then CO2 is removed by the lungs Q: How much Bicarbonate do I have in my body? Bicarbonate concentration in plasma = 24 mmol or mEq /L (both units work) Q: How much is the filtered load of Bicarbonate by day? 180L * 24 =4320 mEq/day That will be 100% reabsorbed Bicarbonate is very important in our body because the kidneys excrete a variable amount of H+ into the urine and conserve Bicarbonate ions HCO3- , which are an important buffer of H+ in the blood. Buffer الدارئة Our body produces around 1mmol/kg (of our bodyweight) acids per day Example: If your body weight is 70 70 mmol acids are produced per day Then your body will need 70mmol of bicarbonate By the end of the day the body will lose 70mmol of bicarbonate So I will expect the kidney not to reabsorb all the filtered bicarbonate only, actually I will produce new bicarbonates So concentration of Bicarbonate will be higher in the Renal Vein When a renal failure occurs the kidney might not be able to reabsorb the original bicarbonates or maybe will not be able to produce new ones this will lead to acidosis Henderson- Hasselbalch equation H+ + HCO3pH = pKa + log (HCO3-/CO2) HCO3- =24 mmol/day CO2 = 1.2 mmol/day So 24/1.2 = 20 pH = 6.1 + log(20) 7.4 = 6.1 + 1.3 When acidosis happen low pH (less than 7.35) the reason is either bicarbonates or CO2 If bicarbonates Metabolic acidosis If CO2 Respiratory acidosis When alkalosis happen high pH (higher than 7.45) the reason is either bicarbonates or CO2 If bicarbonates Metabolic alkalosis If CO2 Respiratory alkalosis Renal Failure will lead to Metabolic Acidosis The function of the kidney in Acid-base balance to reabsorb the filtered Bicarbonates and to produce new ones. This is the end of the Renal System for this course. (L01-L05) Good Luck
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