200 liters of fluid from the blood stream, allowing toxins, metabolic wastes, excess ions to leave as urine while returning the needed substances 99% of the filtrate is reabsorbed, only 1.5 to 2 L pass as urine Kidneys are the major excretory organs P.955 Renin- an enzyme, helps to regulate blood pressure Erythropoietin – an hormone, stimulates RBC production Metabolize vitamin D to its active form Gluconeogenesis during prolonged fasting Kidney Anatomy Bean shaped, lie retroperitoneally Lateral surface is convex Medial surface is concave, has a vertical cleft called renal hilus, that leads within the kidney called renal sinus, contains ureters, blood vessels, lymphatics, and nerves Adrenal gland – sits atop each kidney Kidney Anatomy Renal (fibrous) capsule – Adipose tissue – Renal fascia – P.956 Renal cortex, medulla, and pelvis Renal pyramids – broad base faces toward the cortex; its apex is papilla Minor calyces, major calyces, renal pelvis Nephrons P.957 Renal arteries and renal veins – P.958 Nephrons are the structural & functional units of the kidneys Each kidney contains over 1 million of these tiny blood-processing units; carry out these processes and form urine Each nephron consists of a glomerulus and a renal tubule Glomerular capsule (or Bowman’s capsule) – surrounds the glomerulus Renal corpuscle – glomerular capsule and the enclosed glomerulus Glomerular endothelium is fenestrated (penetrated by many pores which makes these capillaries extremely porous Filtrate – contains everything from blood except protein and blood cells Parietal layer of the glomerular capsule P.960 Visceral layer clings to the glomerulus, consists of highly modified epithelial cells called podocytes Proximal convoluted tubule (PCT) – Loop of Henle - Distal convoluted tubule (DCT) – Collecting ducts – Papillary ducts – deliver urine into the minor calyces Walls of the PCT are cuboidal epithelial U-shaped loop of Henle has descending and ascending limbs; has thin and thick segments Nephron Capillary Beds Glomerulus and peritubular capillaries P.962 Glomerulus, a tuft of capillaries, is specialized for filtration It is both fed and drained by arterioles - affarent and efferent arterioles Arterioles are high resistance vessels Affarent arteriole has a larger diameter than the efferent, makes the BP high Cortical nephrons – 85%, only small parts of the loop of the Henle dip into the outer medulla Juxtamedullary nephrons – are at the cortico-medullary junction; play an important role in the kidney’s ability to produce concentrated urine; their loops of Henle invade deep into the medulla Most of this filtrate (99%) is reabsorbed by the renal tubule cells and returned to blood by the peritubular capillaries Peritubular capillaries, arise from the efferent arterioles, cling closely to the renal tubule and empty into venules Vasa recta – bundles of long straight vessels in the loop of Henle The first capillary bed (glomerulus) produces filtrate The second (peritubular capillaries) reclaims most of the filtrate Juxtaglomerular Complex (JGC) – lies at the juncture of DCT and afferent arteriole P.963 Granular or Juxtaglomerular (JG) cells – secrete renin, act as mechanoreceptors that sense the pressure in the affarent arteriole Macula densa cells – closely packed DCT cells lies adjacent to JG cells; are chemoreceptors (osmoreceptors) that respond changes in the solute content Mechanism of Urine Formation Involve three processes : Glomerular filtration - Tubular reabsorption - Tubular secretion - About 1200 ml of blood passes through the glomeruli each minute; 650 ml is plasma, and 1/5 of this (120 – 125 ml) is forced into the renal tubules Filtrate and urine are quite different Filtrate contains everything found in blood plasma except proteins Mostly metabolic wastes By the time filtrate has reached into the collecting duct most of its water, nutrients, and ions; remains now urine Contains mostly water and unneeded substances Kidneys process about 180 L of fluid daily. Of this amount, only about 1% (1.8 L) actually leaves the body as urine Filtration Membrane P.965 Lies between blood and visceral layer of glomerular capsule Porous membrane that allows free passage of water and solutes smaller than plasma proteins Fenestrated endothelium of glomerular capillaries Podocytes in the visceral membrane Step 1: Glomerular Filtration Glomerular filtration by the glomeruli Tubular reabsorption and secretion in the renal tubules Glomerular filtration – a passive process A more efficient filter than are other capillary beds, because Its filtration membrane has a large surface area and is thousands of times More permeable to water and solutes Glomerular blood pressure is much higher than that in other capillary beds (55 mm Hg as opposed to 18 mm Hg) resulting in a much higher net filtration pressure;as a result of these differences Kidneys produce about 180 L of filtrate daily, as opposed 2 to 4 L daily by other capillary beds of the body combined Net Filtration Pressure (NFP) P.965 Glomerular hydrostatic pressure (HPgc) – chief force pushing water and solutes out of the blood and across the filtration membrane HPg is opposed by two forces: P.966 Colloid osmotic pressure of blood (OPgc) – Capsular hydrostatic pressure(HPcs NFP = HPgc – (OPgc + HPcs) = 55 – (30 + 15) = 10 mm Hg Glomerular filtration rate (GFR) – is the volume of filtrate formed each minute by the combined activity of 2 million glomeruli of the kidneys Factors governing the filtration rate are: (1) total suface area available for filtration (2) filtration membrane permeabilty (3)Net filtration pressure (NFP) Normal GFR is 120 – 125 ml/min GFR is directly proportional to the NFP, any change in any of the pressures would change both the NFP and GFR Renin-angiotensin mechanism P.968 is triggered when various stimuli cause the JG cells to release renin Renin acts angiotesinogen, made by the liver, to make angiotensin I, which is converted to angiotensin II by angiotensin converting enzyme (ACE), a potent vasoconstrictor It also stimulates the adrenal cortex to release aldosterone, which causes renal tubule to reclaim more sodium ions from the filtrate As water follows sodium osmotically blood volume and blood pressure rise Angio II causes efferent arterioles to constrict to a greater extent and thereby increasing HPg Step 2: Tubular Reabsorbtion P.968 It begins as soon as the filtrate enters the proximal tubules To reach the blood, substances move through three membrane barriers – the luminal and basolateral membranes of the tubule cells and the endothelium of the peritubular capillaries Virtually all organic nutrients such as glucose and amino acids are completely reabsorbed On the other hand, water and many ions are continuously regulated and adjusted in response to as needed The reabsorption process is either passive or active Sodium Reabsorption Na+ - passive, active, and passive P.970 Transport maximum (Tm) – for nearly every substances that is actively reabsorbed; it reflects the number of carriers in the renal tubules available to ferry each particular substance When the transporters are saturated – the excess is excreted in urine As plasma levels of glucose exceed 180mg/dl, the glucose Tm is exceeded and large amounts of glucose will be lost in the urine even though the renal tubules are functioning normally H20 - “obliged” to follow salt, called obligatory water reabsorption Nonabsorbed substances – either not reabsorbed or reabsorbed incompletely: urea, uric acid, creatinine Absorptive Capabilities of the Renal Tubules and Collecting Ducts P.970 Proximal Convoluted Tubule – the entire renal tubule is involved in reabsorption to some degree, the PCT cells are by far the most active “reabsorbers” Reabsorbs all of the glucose, lactate, and amino acids; 65% Na and H20, 55% K, 60% Cl, 80% bicarbonate P.971 Nephron Loop – water reabsorption is not coupled to solute reabsorption; water can leave the descending limb of the loop of Henle but not the ascending limb These permeability differences play a vital role in the kidney’s ability to form dilute and concentrated urine P.972 Distal Convoluted Tubule and Collecting Duct – By the time the DCT is reached, only 10% of the filtered NaCl and 25% of the water is there Effect of aldosterone – Na+ reabsorbed, water follows, and excrete K+ Atrial natriuretic peptide (ANP) – Excrete Na+, water follows Step 3: Tubular Secretion Substances such as H+, K+, NH4+, Creatinine, and certain organic substances move from the tubule cells into the filtrate Disposing certain drugs Eliminating undesirable substances Controlling blood pH Regulation of Urine Concentration and Volume P.973 Osmolality – is the number of solute particles dissolved in one liter of water Milliosmol – 1/1000 or 0.001 osmol 300 mOsm, the osmotic concentration of the blood plasma; kidneys play a great role to maintain it Countercurrent mechanism - The term countercurrent means that something flows in opposite direction through adjacent channels Osmolality increases from 300 to about 1200 mOsm in the deepest part of the medulla Countercurrent Multiplier 1. The descending limb of the loop of the Henle is relatively impermeable to solutes and freely permeable to water 2. The ascending limb is permeable to solutes but not to water – filtrate in the ascending limb becomes increasingly dilute until, 100 mOsm at the DCT, it is hypotonic to blood plasma 3. The collecting ducts in the medullary regions are permeable to urea – P.976 Formation of Dilute Urine – when ADH is not released by the posterior pituitary Collecting duct remain impermeable to water, no further water reabsorption Formation of Concentrated Urine – ADH inhibits diuresis or urine output; water passes through the principals cells of the collecting ducts Summary of nephron functions (a) Proximal tubules – nearly all nutrients and 65% Na are absorbed; Cl- and water follows (b) Descending limb – is freely permeable to water but not to NaCl (c) Ascending limb – is impermeable to water but permeable to Na+ and Cl- (d) Distal tubule – more Na+ is reabsorbed in the presence of aldosterone; water permeability is extremely low (e) Collecting duct – is more permeable to urea and is made more so by the presence of ADH In absence of ADH it is nearly impermeable to water, and the dilute urine passes out In presence of ADH,water is reabsorbed and concentrated urine is excreted Renal Clearance P.978 refers to the volume of plasma that is cleared of a particular substance in a given time, usually 1 minute Tests are done to determine the GFR, provides information about the amount of functioning renal tissue Renal Clearance (RC) = UV/P U = conc. of the substance in urine V = flow rate of urine formation P = conc. of the substance in plasma Inulin, a polysaccharide, is often used as the standard to determine GFR, it is not reabsorbed, secreted, or stored Urine Color – clear and pale to deep yellow is due to urochrome, a pigment that results from the body’s destruction of hemoglobin via bilirubin Odor –slightly aromatic, develops an ammonia odor on standing; diabetic urine is smells fruity due to acetone pH – slightly acidic (around pH 6) Specific Gravity – 1.002 to 1.035 Micturition P.982 Voiding or urination – act of emptying the bladder; distension of the bladder walls activates stretch receptors Visceral afferents activate the micturition center, parasympathetic outflow stimulate contraction of detrusor muscle and relaxation of internal and external sphincters