Dr Gihan Gawish Nephron Tubular Component – forms urine Bowman’s capsule Proximal Convoluted Tubule Loop of Henle Distal Convoluted Tubule Collecting duct
Dr Gihan Gawish
Urine Formation Urine - water and waste solutes Nephrons conduct three processes to convert blood plasma into urine 1. filtration filter blood plasma to retain cells/proteins 2. reabsorption remove valuable materials from filtrate 3. secretion transfer additional wastes to filtrate
Dr Gihan Gawish Filtration Filtration driven by blood pressure Glomerular filtration is nonselective – Small particles pass (glucose, Na+, urea, H2O) – Large ones do not 20% of plasma enters tubule – plasma filtered 65x/day
Dr Gihan Gawish Reabsorption Occurs in remainder of nephron tubule Selective movement of substances from tubule into plasma – Return of valuable substances to peritubular caps Active or passive – Passive (no energy) – Active transport (requires energy)
Dr Gihan Gawish Secretions Also occurs in tubules Additional materials transported from plasma in Peritubular capillaries into tubule – excess K+, Ca2+ and H+, uric acid – foreign compounds By passive diffusion or active carrier transport
Dr Gihan Gawish Formation of Urine steps : 1.Blood enters the glomerulus under pressure. 2.This causes water, small molecules (but not macromolecules like proteins) and ions to filter through the capillary walls into the Bowman's capsule. This fluid is called nephric filtrate.
Dr Gihan Gawish Formation of Urine steps 3.Nephric filtrate collects within the Bowman's capsule and then flows into the proximal tubule. 4.Here all of the glucose, and amino acids, >90% of the uric acid, and ~60% of inorganic salts are reabsorbed by active transport. uric acidactive transport 5.The active transport of Na+ out of the proximal tubule is controlled by angiotensin II.angiotensin II 6.The active transport of phosphate (PO43-) is regulated (suppressed by) the parathyroid hormone.parathyroid hormone
Dr Gihan Gawish Formation of Urine steps 7.As these solutes are removed from the nephric filtrate, a large volume of the water follows them by osmosis (80–85% of the 180 liters deposited in the Bowman's capsules in 24 hours).osmosis 8.As the fluid flows into the descending segment of the loop of Henle, water continues to leave by osmosis because the interstitial fluid is very hypertonic.hypertonic 9.This is caused by the active transport of Na+ out of the tubular fluid as it moves up the ascending segment of the loop of Henle. 10.In the distal tubules, more sodium is reclaimed by active transport, and still more water follows by osmosis. 11.Final adjustment of the sodium and water content of the body occurs in the collecting ducts.
Dr Gihan Gawish Formation of Urine steps Sodium Although 97% of the sodium has already been removed, it is the last 3% that determines the final balance of sodium — and hence water content and blood pressure — in the body.blood pressure The reabsorption of sodium in the distal tubule and the collecting ducts is closely regulated, chiefly by the action of the hormone aldosterone.aldosterone
Dr Gihan Gawish Formation of Urine steps Water The hypertonic interstitial fluid surrounding the collecting ducts provides a high osmotic pressure for the removal of water. osmotic pressure Transmembrane channels made of proteins called aquaporins are inserted in the plasma membrane greatly increasing its permeability to water. (When open, an aquaporin channel allows 3 billion molecules of water to pass through each second.)
Dr Gihan Gawish Water Insertion of aquaporin-2 channels requires signaling by vasopressin (also known as arginine vasopressin [AVP] or the antidiuretic hormone [ADH]).vasopressin –Vasopressin binds to receptors (called V2 receptors) on the basolateral surface of the cells of the collecting ducts. basolateral surface –Binding of the hormone triggers a rising level of cAMP within the cell. –This "second messenger" initiates a chain of events culminating in the insertion of aquaporin-2 channels in the apical surface of the cell.apical surface
Dr Gihan Gawish Formation of Urine steps
Dr Gihan Gawish Formation of Urine steps The release of vasopressin (from the posterior lobe of the pituitary gland) is regulated by the osmotic pressure of the blood.pituitary gland Anything that dehydrates the body, such as perspiring heavily, –increases the osmotic pressure of the blood; –turns on the vasopressin → V2 receptors → aquaporin-2 pathway.
Dr Gihan Gawish Formation of Urine steps The result: –As little as 0.5 liter/day of urine may remain of the original 180 liters/day of nephric filtrate. –The concentration of salts in the urine can be as much as four times that of the blood. (But not high enough to enable humans to benefit from drinking sea water, which is saltier still.)
Dr Gihan Gawish Formation of Urine steps If the blood should become too dilute (as would occur after drinking a large amount of water( Vasopressin secretion is inhibited. The aquaporin-2 channels are taken back into the cell by endocytosis.endocytosis The result: a large volume of watery urine is formed (with a salt concentration as little as one- fourth of that of the blood.
Dr Gihan Gawish In 24 hours the kidneys reclaim ~1,300 g of NaCl ~400 g NaHCO3 ~180 g glucose almost all of the 180 liters of water that entered the tubules.
Dr Gihan Gawish Diabetes insipidus This disorder is characterized by: excretion of large amounts of a watery urine (as much as 30 liters — about 8 gallons — each day!) unremitting thirst. It can have several causes: Insufficient secretion of vasopressin. Inheritance of two mutant genes for the vasopressin receptor (V2). Inheritance of two mutant genes for aquaporin-2.
Dr Gihan Gawish The Kidney and Homeostasis The kidney is one of the major homeostatic devices of the body.homeostatic it removes normal components of the blood that are present in greater-than-normal concentrations. When excess water, sodium ions, calcium ions, potassium ions, and so on are present, the excess quickly passes out in the urine. On the other hand, the kidneys step up their reclamation of these same substances when they are present in the blood in less-than-normal amounts. Thus the kidney continuously regulates the chemical composition of the blood within narrow limits.
Dr Gihan Gawish Hormones of the Kidneys The human kidney is also an endocrine gland secreting two hormones: Erythropoietin (EPO)Erythropoietin Calcitriol (1,25[OH]2 Vitamin D3), the active form of vitamin D ( See the Chapter of bone)Calcitriol as well as the enzyme renin.renin
Dr Gihan Gawish 1. Erythropoietin Mechanism Kidney (and liver to a smaller extent) releases erythropoietin Enhanced Erythropoiesis increases RBC count Homeostasis: Normal blood oxygen levels Reduces O2 levels in blood Increases O2-carrying ability of blood Erythropoietin stimulates red bone marrow
Dr Gihan Gawish 2. Role of Calcitriol
Dr Gihan Gawish 3. Regulation of Blood Pressure by Hormones One of the functions of the kidney is to monitor blood pressure and take corrective action if it should drop. The kidney does this by secreting the proteolytic enzyme renin. Renin acts on angiotensinogen, a plasma peptide, splitting off a fragment containing 10 amino acids called angiotensin I. angiotensin I is cleaved by a peptidase secreted by blood vessels called angiotensin converting enzyme (ACE) — producing angiotensin II, which contains 8 amino acids.
Dr Gihan Gawish Regulation of Blood Pressure by Hormones
Dr Gihan Gawish Regulation of Blood Pressure by Hormones angiotensin II constricts the walls of arterioles closing down capillary beds;closing down capillary beds stimulates the proximal tubules in the kidney to reabsorb sodium ions;proximal tubules stimulates the adrenal cortex to release aldosterone. Aldosterone causes the kidneys to reclaim still more sodium and thus wateraldosterone increases the strength of the heartbeat; stimulates the pituitary to release the vasopressin.vasopressin All of these actions, which are mediated by its binding to G-protein- coupled receptors on the target cells, lead to an increase in blood pressure.G-protein- coupled receptors
Dr Gihan Gawish The Artificial Kidney The artificial kidney uses the principle of dialysis to purify the blood of patients whose own kidneys have failed.