Functional Anatomy of the Nephron PDF

Functional anatomy of the nephron ○ Each individual renal tubule and its glomerulus is a unit (nephron). ○ The size of the kidneys between species varies, as does the number of nephrons they contain ○ each human kidney has approximately 1 million nephrons ○ The glomerulus, which is about 200 um in D...

Functional anatomy of the nephron ○ Each individual renal tubule and its glomerulus is a unit (nephron). ○ The size of the kidneys between species varies, as does the number of nephrons they contain ○ each human kidney has approximately 1 million nephrons ○ The glomerulus, which is about 200 um in Diameter, is formed by the invagination of a tuft of capillaries into the dilated, blind end of the Nephron (Bowman’s capsule) ○ the capillaries are supplied by an afferent arteriole and drained by the efferent arteriole, and it is from the glomerulus that the filtrate is formed ○ the diameter of the afferent arteriole is larger than the efferent arteriole ○ two cellular layers separate the blood from the glomerular filtrate in Bowman’s capsule: the capillary Endothelium and the specialized epithelium of the capsule ○ the endothelium of the glomerular capillaries is fenestrated, with pores that are 70 to 90 nanometers in diameter. ○ the endothelium of glomerular capillaries is completely surrounded by the glomerular basement membrane along with specialized cells called podocytes ○ Podocytes Have numerous pseudopodia that interdigitate to form filtration slits along the capillary wall ○ the slits are approximately 25 nanometers wide and each is closed by a thin membrane Regulation of the renal blood flow ○ Norepinephrine (noradrenaline) constricts the renal vessels, with the greatest effect of injected norepinephrine being exerted on the interlobular arteries and the afferent arterioles. ○ dopamine is made in the kidney and causes renal vasodilation and natriuresis ○ and you tends into exerts a constrictor effect on both the afferent and efferent arterioles ○ prostaglandins increase blood flow in the renal cortex and decrease blood flow in the renal medulla ○ acetylcholine also produces renal vasodilation ○ a high protein diet raises glomerular capillary pressure and increases renal blood flow Auto regulation of renal blood flow ○ when the kidney is perfused at moderate pressures (90 to 220 mmHg in the dog) the renal vascular resistance varies with the pressure so that renal blood flow is relatively constant ○ Auto regulation of this type occurs in other organs and several factors contribute to it ○ renal autoregulation is present in denervated and in isolated, perfused kidneys but is prevented by the administration of drugs that paralyze vascular smooth muscle ○ it is probably produced in part by a direct contractile response to stretch of the smooth muscles of the afferent arteriole ○ NO may also be involved ○ at low perfusion pressures, Angiotensin 2 also appears to play a role by constricting the efferent arterioles thus maintaining the GFR ○ this is believed to be the explanation of the renal failure that sometimes develops in patients with poor renal perfusion who are treated with drugs that inhibit Angiotensin converting enzyme Glomerular filtration: measuring GFR ○ GFR is the amount of plasma ultrafiltrate formed each minute and can be measured in intact experimental animals and humans by measuring the plasma level of a substance and the amount of that substance that is excreted ○ A substance to be used to measure GFR must be freely filtered through the glomeruli and must be neither secreted nor reabsorbed by the tubules ○ in addition to the requirement that it be freely filtered and neither reabsorbed nor secreted in the tubules, a substance suitable for measuring the GFR should be non-toxic and not metabolized by the body ○ Inulin, a polymer of fructose with a molecular weight of 5200, meets these criteria in humans and most animals and can be used to measure GFR hydrostatic and osmotic pressure ○ the pressure in the glomerular capillaries is higher than that in other capillary beds because the afferent arterioles are short, straight branches of the interlobular arteries ○ Furthermore the vessels Downstream from the glomeruli, the efferent arterioles, have a relatively High Resistance. The capillary hydrostatic pressure is opposed by the hydrostatic pressure in Bowman's capsule. ○ it is also opposed by the oncotic pressure gradient across the glomerular capillaries ○ (pi)T is negligible and the gradient is essentially equal to the oncotic pressure of the plasma proteins Factors affecting the GFR ○ Changes in renal blood flow ○ Changes in glomerular capillary hydrostatic pressure ○ Changes in systemic blood pressure ○ Afferent or efferent arteriolar constriction ○ Changes in hydrostatic pressure in Bowman capsule ○ Ureteral obstruction ○ Edema of kidney inside tight renal capsule ○ Changes in concentration of plasma proteins: dehydration, hypoproteinemia, etc (minor factors) ○ Changes in Kf ○ Changes in glomerular capillary permeability ○ Changes in effective filtration surface area Loop of Henle ○ The loops of Henle of the juxtamedullary nephrons dip deeply into the medullary pyramids before draining into the distal convoluted tubules in the cortex, and all the collecting ducts descend back through the medullary pyramids to drain at the tips of the pyramids into the renal pelvis ○ there is a graded increase in the osmolality of the interstitium of the pyramids and humans: the osmolality at the tips of the papillae can reach about 1,200 mOsm/kg of H2O, Approximately four times that of plasma ○ the descending limb of the loop of Henle is permeable to water, due to the presence of aquaporin 1 in both the apical and Basolateral membranes, but the ascending limb is impermeable to water ○ Na+, K+, and Cl- are co Transported out of the thick segment of the ascending limb ○ therefore the fluid in the descending limb of the loop of Henle becomes hypertonic as water moves out of the tubule into the hypertonic interstitium ○ in the ascending limb it becomes more dilute because of the movement of na+ and Cl- out of the tubular lumen, and one fluid reaches the top of the ascending limb( call the diluting segment) it is now hypotonic to plasma ○ In passing through the descending Loop of Henle, another 15% of the filtered water is removed, so approximately 20% of the filtered water enters the distal tubule, and the TF/P of inulin at this point is about five regulation of water excretion Water diuresis ○ the feedback mechanism controlling vasopressin secretion and the way vasopressin secretion is stimulated by a rise and inhibited by a drop in the effective osmotic pressure of the plasma are discussed in chapter 17 ○ the water diuresis produced by drinking large amounts of hypotonic fluid begins about 15 minutes after ingestion of a water load and reaches its maximum in about 40 minutes ○ the act of drinking produces a small decrease in vasopressin secretion before the water is absorbed, but most of the inhibition is produced by the decrease in plasma osmolality after the water is absorbed water intoxication ○ ○ ○ ○ ○ during excretion of an average osmotic load, the maximal urine flow that can be produced during a water diuresis is about 16 ml/min if water is ingested at a higher rate than this for any length of time, swelling of the cells become severe because of the uptake of water from hypotonic ECF and rarely the symptoms of water intoxication May develop swelling of the cells in the brain cause convulsions and coma and leads eventually to death water intoxication can also occur when water intake is not reduced after administration of exogenous vasopressin or when secretion of endogenous vasopressin occurs and response to non-osmotic stimuli such as surgical trauma Administration of oxytocin after parturition (to contract the uterus) can also lead to water intoxication if water intake is not monitored carefully