RENAL Structure and function of the renal tubule Flashcards

Question

Thick Ascending Loop of Henle ``` Role? How does Na+ enter cell from lumen? How does Na+ exit cell into blood? what about entry and exit of K+ and Cl-? what effects for loop diuretics have? examples of loop diuretics? what does this result in and why? ```

Answer 1

The thick ascending LoH reabsorbs approx. 25% of filtered Na and can compensate partially for any failure by PCT to reabsorb Na. Na enters cell via Na: K: 2Cl cotransporter (or symporter), the driving force of which is large electrochemical difference favoring entry of Na into the cell. • To exit, Na is transported actively via Na-K-ATPase, while K and Cl cross into the peritubular fluid passively. The inhibition of the Na: K: 2Cl transporter by loop diuretics, results in inhibition of net NaCl reabsorption and increased excretion of these ions along with water. (Furosemide and bumetanide) By disrupting the reabsorption of these ions, loop diuretics prevent the generation of the medullary osmotic gradient. Without such a concentrated medulla, water has less of an osmotic driving force to leave the collecting duct system, ultimately resulting in increased urine production.

Answer 2

Blood flow in VR is low ~5% of renal blood flow » minimizes solute loss from interstitium & maintains medullary interstitial gradient Alteration of blood flow in VR can change gradient The osmotic gradient of the medullary is maintained by the counter current and Vasa Recta The vasa recta delivers O2 and nutrients to cells of the loop of Henle. The vasa recta, like other capillaries, is permeable to both H2O and salts and could disrupt the salt gradient established by the loop of Henle. To avoid this, the vasa recta acts as a counter-current multiplier system as well. As the vasa recta descends into the renal medulla, water diffuses out into the surrounding fluids, and salts diffuse in. When the vasa recta ascends, the reverse occurs. As a result, the concentration of salts in the vasa recta is always about the same, and the salt gradient established by the loop of Henle remains in place. Water is removed by VR, so it doesn’t dilute the longitudinal osmotic gradient. The medullary blood flow in the VR is slow, which is sufficient to supply the metabolic needs of the tissue but minimise solute loss from the medullary interstitium. Reabsorbed Na+ in descending VR is carried to inner medulla equilibrating with ISF -> ↑ regional osmolarity Na+ in ascending VR returns to systemic circulation. The amount of solute in the ascending VR is a product of flow rate & concentration - e.g. If blood flow in VR increases then solutes are washed out of the medulla and its interstitial osmolality is decreased. If blood flow is decreased, then the opposite happens.

Answer 3

DCT: -> 1st part (macula densa) linked to juxtaglomerular complex Provides feedback control of GFR & tubular fluid flow in the same nephron ->2nd part very convoluted Connecting Tubule: Connects end of DCT to collecting duct – mainly in outer cortex Overlap in functional characteristics with 2nd part of DCT

Answer 4

o Solute reabsorption continues, w/out H2O reabsorption o High Na+, K+-ATPase activity in basolateral membrane o Very low H2O permeability o Further dilution of tubular fluid o Anti-diuretic hormone (ADH) can exert actions o Role to play in acid-base balance via secretion of NH3

Answer 5

Collecting ducts formed by joining of collecting tubules o Cuboidal epithelia, very few mitochondria 2 types of cells: o Intercalated cells - Involved in acidification of urine and acid-base balance o Principal cells - Role to play in Na balance & ECF volume regulation

Answer 6

Your body makes ADH in the hypothalamus and stores the hormone in your pituitary gland. ADH then concentrates the urine by triggering the kidney tubules to reabsorb water back into your bloodstream rather than excreting water into your urine. The single most important effect of antidiuretic hormone is to conserve body water by reducing the loss of water in urine. The most important variable regulating antidiuretic hormone secretion is plasma osmolarity, or the concentration of solutes in blood. Osmolarity is sensed in the hypothalamus by neurons known as an osmoreceptors, and those neurons, in turn, simulate secretion from the neurons that produce antidiuretic hormone. When plasma osmolarity increases above the threshold, osmoreceptors recognise this -> stimulate the neurons that secrete antidiuretic hormone. Secretion of ADH is mediated primarily by hypothalamic osmoreceptors, which monitor changes in plasma osmolality. - ADH secretion can also be regulated by volume receptors and arterial baroreceptors. At a cellular level, Binding of AVP to V2-receptors stimulates the synthesis of aquaporin-2 water channel proteins and promotes cAMP-dependent trafficking of aquaporin 2 water channels to the luminal membrane of principal cells allowing back diffusion of water down its concentration gradient. Vasopressin via V2 receptors also activates urea transporters in the distal nephron to facilitate urea reabsorption and urea recycling, which allows maximisation of sodium reabsorption in the thick ascending limb, supporting the axial hyperosmotic gradient drawing water from the distal nephron.

Answer 7

Urea is a waste product formed in the liver during metabolic breakdown of proteins. You would imagine that the majority of urea would be excreted from the body via urine, but it is not. Urea filters freely through glomerulus and passes down the tubule. Unlike cortical collecting tubule, the medullary collecting duct is permeable to urea. As water is reabsorbed from the CD the urea is concentrated so that it moves out of the CD and is absorbed into the surrounding capillaries and also into the interstitium of the medulla where it contributes to the osmotic gradient around the LoH. Increasing levels of urea in kidney is a sign of pre-renal failure because reabsorption is enhanced. Monitored using blood urea nitrogen test (BUN).

Answer 8

The tubular fluid which enters the CD system is always hypo-osmotic and its concentration or further dilution as it traverses the CD depends on the water permeability of the duct, which is determined by the action of ADH. In the presence of ADH water permeability is increased. ADH acts by inducing synthesis and insertion of water channels (aquaporins) into the luminal membrane. Water is reabsorbed along the osmotic gradient and the urine osmolarity approaches that of the medullary ISF at the tips of the long loops of Henle. Water reabsorption increases the CD urea concentration and ADH increases the duct permeability to urea and therefore its reabsorption is increased. - Other solutes, particularly Na+ and Cl-, continue to be reabsorbed in the CD and this further solute reabsorption serves to maintain the medullary hyper-osmolarity and thus facilitates the reabsorption of water in the presence of ADH. - The final urine volume may be as low as 0.5 to 1.0 % of the filtered load and its concentration as high as 1400 mOsm/L. In the absence of ADH the CD becomes essentially impermeable to water and urea. Sodium reabsorption continues in the CD and the tubular fluid become progressively more dilute in its progress along the duct. The volume of urine excreted under these conditions is potentially very large. Under conditions of water deprivation, ADH acting through its receptor opens water channels in the epithelium so that water is extracted osmotically by the osmotic gradient set up in the interstitium around the LoH. However, under conditions of water excess, ADH secretion falls, the water channels close and this facultative reabsorption of water cannot occur -> get large volume of dilute urine resulting.

Answer 9

About 65% of the glomerular filtrate is reabsorbed proximally and another 10 % in the loop of Henle. The 25 % remaining enters the CD.

Answer 10

At the average normal GFR of 180 L/day this is 36 L/day. In the presence of ADH only 1 to 2 L is excreted. In the absence of ADH all of this volume may be excreted and may have an osmolarity as low as 50 mOsm/L.

Answer 11

An individual excreting large volume of dilute urine is said to be in a state of water diuresis.

Answer 12

1. Active transport of Na+ and co-transport of K+ & Cl- out of thick ascending limb into medullary interstitium 2. Active transport of ions from collecting ducts into medullary interstitium 3. Facilitated diffusion of large amounts of urea from collecting ducts into medullary interstitium 4. Very little diffusion of water from ascending limbs of tubules into medullary interstitium

Answer 13

• Polycystic Kidney Disease (PKD) - Genetic disorder characterised by growth of numerous cysts in kidney • Diseases of the glomerulus -> Usually called glomerulonephritis (GN) – inflammation of glomeruli of some or all of million nephrons in kidney – Can be primary or secondary to systemic disease like diabetes mellitus -> Inherited diseases of the glomerular basement membrane • Diseases of the tubules - Obstruction (reducing glomerular filtration) - Impairment of transport functions (reducing water & solute reabsorption) e.g. Fanconi’s syndrome.

Answer 14

- Hypertension o Kidneys regulate ECF volume and hence influence blood pressure  compensatory mechanisms in response to high BP can lead to chronic kidney damage - Congestive Cardiac Failure o Fall in cardiac output  renal hypoperfusion  registered as hypovolaemia, compensation results in pulmonary oedema - Diabetic nephropathy o As a consequence of diabetes, filtering system of kidneys gets destroyed over time - Lithium treatment results in acquired nephrogenic diabetes insipidus o Due to reduction of AQP2 expression.