Last lec we have studied what controls GFR; either high or low GFR are bad and how to measure GFR. Today we will talk about the tubules.

Transcription

1 Last lec we have studied what controls GFR; either high or low GFR are bad and how to measure GFR. Today we will talk about the tubules. In the tubules first thing we have urine formation; which is the ultra filtration (Means the process by which large molecules that are essential to the body are filtered out so that they can be reabsorbed. In turn the small molecules such as water, amino acids and urea are passed through other parts of the kidney such as loop of Henle and the distal convoluted tubule, and they form urine)wiki; so when we talk about glucose concentration in the filtrate will be the same as in the plasma; M.W of glucose g mol 1 so it is freely filtered. Note: anything with a M.W under is freely filtered; to measure the filtration rate we can use neutral, cationic, and anionic dextrans. Cationic dextran will shifts the curve upwards coz all membrane endothelial are negatively charged so filtration is easier while anionic dextran will shifts it downwards -In the pic below If the [glucose] is mg/dl in the afferent arteriole it will be the same in area 1***same as Na; k; Ca coz it is freely filtered. NOTE: There is no glucose in the urine; it is totally reabsorbed. -

2 *Micro puncture technique: Technique used to evaluate renal function at the single nephron level; firstly we use micropipette with small diameter to take samples from the ultra filtrate; then we analyze the samples to know their composition. Q: at which part of the nephrone glucose is being reabsorbed? I know for sure that there is glucose at the beginning of the nephrone and there is no Glu in the urine by taking samples; next I do a nephrone puncture by a micro puncture technique to isolate a piece of the whole course; then I compare the [glucose] at the beginning of the isolated part and its end. If the [glucose] is the same there is no absorption for this part; but if there is any change like from 100mg/dl to 0 mg/dl this means absorption occurred at this part with efficiency 100%. **there is no absorption for glucose in the bowman's space(just filtration) Now we have some acalculia :p Glucose deliver load= 125 mg/min (125mg of glucose is delivered to proximal tubule each min) [Glucose]=100mg/dl In order to find out the tubular load we multiply by 1.25 of the concentration of the glucose.

3 *Transport of Glucose: As glucose concentration increases in the plasma, the filtered load increases. This is a linear relationship because filtration is an entirely passive process. Since glucose reabsorption is coupled to sodium transport by means of secondary active transport (need Na), there is a limit to the rate at which glucose can be transported. This limit is referred to as transport maximum, Tm. Tm: can be defined as the maximum capacity of the proximal tubular cells to transport glucose from the lumen to renal interstitial fluid and back into the blood, It averages about 375 mg/min. Secondary active transport has three properties: 1. stereospecificity 2.compition3.saturation(anything exceeds the T max will be excreted) At the basolateral membrane (active membrane) a layer of mitochondria whose ATP is used to excrete Na through a Na-K pump; actually 80% of the kidney's energy is used for this mission. Glucose titration curve:

4 As well as glucose load is less than 375 mg/min which corresponds to a plasma glucose concentration of 320 mg/dl. Theoretically filtered glucose must be reabsorbed completely and therefore glucose should not appear in urine. Beyond this maximum level glucose will be detected in urine, a condition known as glycosuria. Some of the sodium-glucose carriers have low affinity. This means that unless you have supra-saturated concentrations, you will not guarantee the reabsorption of the entire 320 mg/dl. If plasma glucose concentration was 320 mg/dl some of the glucose molecules will actually escape and appear in urine. This explains the splay observed in the graph. Splay: when glucose appears in the urine before the T max. Threshold for glycosuria: the glucose will appear at the urine when its concentration reaches 180 mg/100ml. So, as long as the glucose concentration below 180, there's no glucose in the urine. If someone had glucose in the urine we should test the glucose concentration in the plasma. If the concentration is normal, it isn't diabetogenic glycosuria, and it is nephrogenic glycosuria because the number of carriers in the kidney is less than normal it isn't a serious condition not bad prognosis not associated with any other abnormality we shouldn't mention it to the person(he isn't a patient at all). Does the kidney participate in glucose homeostasis? (i.e. Does the kidney participate in keeping glucose blood level within the normal physiological range?) No, because the threshold for Tmax is away from the normal physiological concentration of glucose. the kidneys cannot increase plasma glucose levels when they decline under physiological conditions (this does not include the process of gluconeogenesis in the kidneys during starvation conditions) and cannot get rid of extra glucose when plasma glucose levels elevate considerably to mg/dl and will still reabsorb the entire amount of glucose filtered. - If glucose levels decreased to below the normal, say less than 60 mg/dl, the kidneys will not compensate for this decline and will not attempt to increase plasma glucose levels. Similarly, if fasting glucose level exceeded 126 mg/dl, the kidneys will still reabsorb the entire amount of glucose filtered. *SO kidneys don t contribute to glucose homeostasis Note: glucose is being reabsorbed totally in the proximal tubule.

5 -Function of the kidney in phosphate (H 2 PO 4 -) homeostasis: Phosphate concentration in the plasma around 1 mmol/l; freely filtered and it's being reabsorbed under the T max phenomena which equals.1 mm/min; if we drink too much milk plasma phosphate concentration will become 2 and this allows kidney to contribute in phosphate homeostasis through stimulating excretion. Now why kidney plays a role in phosphate homeostasis but not in glucose? Coz T max of phosphate is close to the physiological level of plasma concentration unlike glucose. *Note: avg M.W of amino acids = 110; then it's freely filtered because its lower than 70,000. And it's being reabsorbed by secondary active transport with sodium. *there are three families of carriers for amino acids because there are three types of amino acids: acidic, basic and neutral. *also we have some specific carriers for some amino acids like cysteine, and when this carrier is missing it will lead to cystinurea and cysteine will act as a nucleus for stone formation. ****** Now we will talk about sodium and we are still talking about proximal tubules As doc faraj said in proximal tubule the filtrate will be iso osmotic to the plasma concentration why? Coz we have absorbed relatively same concentration of Na than that of water; Law concentration of sodium = relative reabsorbtion of Na / relative reabsorbtion of water. So let's say we have absorbed 50% of Na in the proximal tubules, we also have absorbed 50% of water coz water follows Na. But to know how much water is reabsorbed so we can determine how much sodium is reabsorbed we need to inject a material that is freely filtered but not reabsorbed (but secreted in urine) called inulin. Practice example: if inulin concentration was 1mg/dl and it became 3mg/dl this means that 2/3 of water has been reabsorbed (inulin as we said is not reabsorbed).and if it became 2mg/dl this means ½ of water has been reabsorbed.

6 Clearance Means volume of plasma cleaned from substance x per minute or provide x for excretion per minute. Example: Clearance of sodium across proximal tubule = (tubular fluid of Na *single nephrone GFR)/plasma Na. ***at the same time; we measure Na we measure inulin clearance = (tubular fluid of inulin *single nephrone GFR)/plasma inulin. Then we divide the two clearances of Na over inulin; Single nephrone GFR is hard to will be omitted, the Na started as 140 and ended as 140 so the ratio is 1 but the ratio for inulin is 3/1. So; clearance of Na /clearance of inulin across the proximal tubule = 1/3; which means that 1/3 Na has reached the urine so 2/3 has been reabsorbed. If the clearance was 1 this means that there is no absorbtion for Na. Kidney is the major way to threw Na out of the system. *Note: concentration of K in the plasma=4; if it reaches 7 the patient will die because of cardiac arrthiema. Sry for being late and sry if there is any mistakes Special thanks to: M3ta9im al Sayed;Amjad Sahrabati; Ody Halholi.

7