Renal Flow and Filtration PDF

Renal flow and filtration ● ● ● ● ● ● ● ● Renal Blood flow is filtered in the glomerulus ---> portion filter = GFR ○ GFR = FF x RPF GFR = amount of filtrate produced per unit time Clearance = volume of plasma that is cleared from a substance ○ Clearance = filtration + secretion - reabsorption Creatinine...

Renal flow and filtration ● ● ● ● ● ● ● ● Renal Blood flow is filtered in the glomerulus ---> portion filter = GFR ○ GFR = FF x RPF GFR = amount of filtrate produced per unit time Clearance = volume of plasma that is cleared from a substance ○ Clearance = filtration + secretion - reabsorption Creatinine is used to measure GFR ○ Freely filtered but NOT reabsorbed and only slightly secreted ○ If Creatinine is high in the plasma then the kidney is not filtering appropriately ----> low GFR ○ Tends to overestimates GFR because creatinine is slightly secreted Inulin Clearance is the gold standard for GFR estimation but is not clinically use ○ Gold standard bc no secretion or reabsorption of Inulin so only measures filtration High BUN is also a indicator of low GFR Sudden drop in GFR is termed Acute Kidney Injury (AKI) There are different types of AKI ○ Prerenal azotemia ■ Decrease in blood flow to the kidney (problem is before kidney) ■ Leads to accumulation of nitrogen waste ---> increases BUN (blood urea nitrogen) ■ note : azotemia means “nitrogen in blood” ■ Atherosclerosis and ischemic nephropathy are examples of prerenal azotemia ● Causes stenosis of left renal artery ○ Postrenal azotemia ■ Decreased urine outflow from kidney usually due to obstruction ■ Ex: kidney stones Tubular Transport ● ● Proximal Tubule ○ Most reabsorption occurs here ○ Na reabsorption is an active process ■ Glucose, amino acids and phosphate are co-transported with Na across apical (secondary active) ○ Na/K ATPase drive reabsorption of molecules and ions across basolateral membrane ○ Na/H pump countertransport drives secretion of H+ ○ Carbonic Anhydrase Inhibitors ■ Used to treat glaucoma because they inhibit the formation of aqueous humor ■ Suppress bicarbonate reabsorption ○ Fanconi’s Syndrome ■ Impaired reabsorption in proximal tubule. Water, glucose, amino acids, bicarb and phosphate wasted in urine instead of being reabsorbed Loop of Henle ○ Na/K/Cl transported in ascending limb drives the transport ■ Leads to paracellular reabsorption of Ca and Mg through an electrochemical gradient that is generated ○ High permeability to water and low permeability to Na or Cl and no active transport ○ Countercurrent exchange mechanism: water leaves descending via descending vasa recta and re-enters the ascending via ascending vasa recta Tubular Transport Cont. ● ● ● Classes of Diuretic agents ○ Loop Diuretics: work in loop of Henle by blocking Na/K/Cl pump ■ Ex: Furosemide can result in excess loss of K (hypokalemia) and decreased paracellular transport of Ca and Mg (hypercalciuria) ■ Clinical Correlation: Bartter Syndrome is a mutation in the Na/K/Cl cotransporter and can lead to similar symptoms as diuretic abuse like hypokalemia, hypercalciuria and polyuria ○ Thiazide Diuretics: work in early distal tubule by blocking NaCl channels ■ Can result in hypokalmeia and hypocalciuria ■ Difference**** thiazide diuretics increase Ca reabsorption (loop decrease it) ■ Clinical Correlation: Gitelman Syndrome mimic thiazide diuretics ○ K sparing Diuretics: work in collecting duct by blockin K secretion Glucose is ONLY reabsorbed in proximal tubule ---> if found in urine ---> diabetes Distal Tubule ○ Fine Tuning Balance of Na, K and water regulated by ADH and Aldosterone ○ Principal cells reabsorb Na and secrete K ○ Intercalated cells secrete H and reabsorb K ■ Alpha: H secretion (a for acid) ■ Beta: bicarb secretion (b for bicarb) ○ Aldosterone ■ Stimulates Na/K ATPase, promotes Na reabsorption and K secretion by working on the N/K pump of the principal cells ○ ADH ■ Makes cells more permeable to water ■ Results in greater reabsorption of water (antidiuretic) Acids/Base Balance ● ● ● ● ● Normal Blood pH = 7.4 ○ <7.38 ---> acidosis ○ >7.44 ---> alkalosis ○ pH = -log[H+] ---> large changes in H are only small changes in pH ○ H2O +CO2 = H2CO3 = H + HCO3 ■ Increase in CO2 or decrease in HCO3 ---> acidosis ■ Increase in HCO3 or decrease in CO2 ----> alkalosis Alpha Intercalated Cells ○ Responds to metabolic acidosis by increasing the secretion of H+ to the kidney ---> excreting more H+ ○ Remember in these cells H+ secretion is linked with K+ reabsorption ■ Therefore increasing H+ secretion ---> hyperkalemia and vice versa Beta Intercalated cells ○ Responds to metabolic alkalosis by increasing the secretion of HCO3 to the kidney ---> excreting more HCO3 Bicarb Reabsorption ○ Primarily takes place in the proximal tubule ○ Remember: bicarb cannot be reabsorbed, it must first be broken down into H20 and C02 by carbonic anhydrase H+ Secretion ○ Happens is the proximal and distal tubules ○ The breakdown of bicarb results in a large amount of H+ in the tubular lumen ○ This stops the process of H+ secretion and actually leads to H+ being reused by carbonic anhydrase ○ In order to combat this we form buffers Acid/Base Disorders ● ● ● Respiratory Acid-Base Disorders --> change in CO2 due to inadequate lung ventilation ○ Compensation is via the kidneys ○ Respiratory Acidosis ■ Increase in PCO2 ----> usually due to decreased ventilation rate ■ Ex: obstructive lung disease like asthma or COPD (remember it is hard to breathe air out in these diseases meaning you are expelling less CO2 and therefore it builds up in the body) ○ Respiratory Alkalosis ■ Decrease in PCO2 -----> usually due to increased ventilation rate ■ Ex: anxiety causes you to hyperventilate leading to more expulsion of CO2 from the body and therefore for alkalosis Metabolic Acid-Base Disorders ---> change in HCO3 ○ Compensation is via lungs or kidneys or both ○ Metabolic Acidosis ■ Loss of bicarb or gain of H ■ Ex: diabetic ketoacidosis causes an excess gain of H or diarrhea can cause an excess loss of HCO3 ○ Metabolic Alkalosis ■ Gain of bicarb or loss of H ■ Ex: vomiting causes a loss of stomach acid leading to a loss of H Anion Gap ○ [Na] - ([Cl] + [HCO3]) ○ High anion gap metabolic acidosis = GOLD MARK ■ Glycols, oxoproline, L-lactate, D-lactate, methanol, aspirin, renal failure, ketones ○ Normal anion gap metabolic acidosis = metabolic acidosis where no organic acids have accumulated Calcium, Phosphate and Magnesium ● ● ● ● ● ● Phosphate levels are opposite the levels of Calcium ○ When phosphate levels are high it binds free calcium decreasing Ca levels. Calcium and Phosphate balance is regulated by: ○ Parathyroid hormone, Vitamin D, Calcitonin Diuretics: ○ Loop diuretics inhibit calcium reabsorption by blocking the Na/Cl/K pump which causes there to be no solvent drag ---> no reabsorption ○ Thiazide diuretics inhibit the Na/Cl transporter which stops the Na/K transported, this increases the activity of Na/Ca transporter to feed the Na/K pump PTH Functions: ○ Acts to increase plasma Calcium by stimulating osteoclasts to resorb bone and the kidneys to reabsorb Ca ○ Stimulates calcitriol production ---> increased Ca absorption in GI tract ○ Decreases plasma phosphate level by increasing phosphate excretion by kidneys ○ Stimulated by low Ca levels ○ Hyperparathyroid --> primary is adenoma and secondary is due to kidney failure bc kidney cannot excrete phosphate, the phosphate binds Ca and PTH is secreted Hyperphosphatemia ○ Can be caused by renal failure bc renal tubule cannot excrete phosphate appropriately. Leads to decreased calcitriol production --> decreases GI absorption of Ca Magnesium ○ Loop diuretics inhibit magnesium reabsorption by decreasing the solvent drag ○ Thiazide diuretics cause excess loss of Mg by increased flow of filtrate (washout) and through blocking of Mg channels in the distal tubule ■ Gitleman’s Syndrome: genetic defect in Na/Cl cotransporter in distal tubule. This transporter is linked to the Mg channel, by blocking it you block Mg