Renal Flashcards
What is renal clearance and what is the equation?
Renal clearance is the volume of plasma completely cleared of a substance by the kidneys per unit time
GFR=
What is the clearance of albumin and glucose?
Albumin and glucose clearance is approximately zero- albumin is not filtered across the glomerular capillaries and glucose is filtered and then completely reabsorbed back into the bloodstream
What is the clearance of Na+, urea, phosphate and Cl-
Na+, urea, phosphate, and Cl− have clearances that are higher than zero- they are filtered and partially reabsorbed
What is the clearance of inulin?
Inulin is freely filtered across the glomerular capillaries, but it is neither reabsorbed nor secreted → its clearance measures the GFR.
What is the clearance ratio?
Inulin is the only substance which its clearance is exactly equal to the GFR.
The clearance of any substance (x) can be compared with the clearance of inulin and is expressed as the clearance ratio.
What is the response to water deprivation?
1.Water is continuously lost from the body in sweat and in water vapor from the mouth and nose (called insensible water loss). If this water is not replaced by drinking water, then plasma osmolarity increases.
2.The increase in osmolarity stimulatesosmoreceptorsin the anterior hypothalamus, which are exquisitely sensitive and are stimulated by increases in osmolarity of less than 1 mOsm/L.
3.Stimulation of the hypothalamic osmoreceptors has two effects. It stimulatesthirst,which drives drinking behaviour. It also stimulates secretion ofADHfrom the posterior pituitary gland.
4.The posterior pituitary gland secretes ADH. ADH circulates in the blood to the kidneys, where it produces an increase in water permeability of the principal cells of the late distal tubule and collecting duct.
5.The increase in water permeability results in increased water reabsorption (5a) in the late distal tubule and collecting ducts. As more water is reabsorbed by these segments,urine osmolarity increasesandurine volume decreases(5b).
6.Increased water reabsorption means that more water is returned to the body fluids. Coupled with increased thirst and drinking behaviour, plasma osmolarity is decreased, back toward the normal value. This system is an elegant example of negative feedback, in which the original disturbance (increased plasma osmolarity) causes a set of feedback responses (secretion of ADH and increased water reabsorption) that restore plasma osmolarity to its normal value.
What is the response to water drinking?
1.When a person drinks water, the ingested water is distributed throughout the body fluids. Because the amount of solute in the body is unchanged, the added water will dilute the body fluids and cause a decrease in plasma osmolarity.
2.The decrease in plasma osmolarity inhibits osmoreceptors in the anterior hypothalamus.
3.Inhibition of the osmoreceptors has two effects. It decreases thirst and suppresses water drinking behavior. It also inhibits secretion of ADH from the posterior pituitary gland.
4.When ADH secretion is inhibited, circulating levels of ADH are reduced and less ADH is delivered to the kidneys. As a result of the lower ADH levels, there is a decrease in water permeability of the principal cells of the late distal tubule and collecting ducts.
5.The decrease in water permeability results in decreased water reabsorption by the late distal tubule and collecting ducts (5a). The water that is not reabsorbed by these segments is excreted,decreasing urine osmolarityandincreasing urine volume(5b).
6.Because less water is reabsorbed, less water is returned to the circulation. Coupled with the inhibition of thirst and the suppression of water drinking, plasma osmolarity increases back toward the normal value.
What is the corticopapillary gradient?
- Is a gradient of osmolarity in the interstitial fluid of the kidney from the cortex to the papilla
- The osmolarity of the cortex is approximately 300 mOsm/L, like the osmolarity of other body fluids.
- Moving from the cortex to the outer medulla, inner medulla, and papilla, the interstitial fluid osmolarity progressively increases.
- At the tip of the papilla, the osmolarity can be as high as 1200 mOsm/L
What solutes contribute to the osmotic gradient, and what mechanisms deposit these solutes in the interstitial fluid?
- countercurrent multiplication: a function of the loop of Henle, which deposits NaCl in the deeper regions of the kidney.
- urea recycling, a function of the inner medullary collecting ducts, which deposits urea
What is countercurrent multiplication?
1) NaCl is pushed out of the NKCC cotransporter in the thick ascending limb (impermeable to water)
2) this increases the osmolarity in the interstitial fluid
3) the descending limb is permeable to water so it will move out until osmolarity increases to the level of the interstitial fluid
4) this process repeats as fluid moves
What is urea recycling?
1.In thecortical and outer medullary collecting ducts,ADH increases water permeability, but it does not increase urea permeability. As a result, water is reabsorbed from the cortical and outer medullary collecting ducts, but urea remains behind in the tubular fluid.
2.This differential effect of ADH on water and urea permeability in cortical and outer medullary collecting ducts causes the urea concentration of tubular fluid to increase.
3.In theinner medullary collecting ducts,ADH increases water permeabilityandit increases the transporter for facilitated diffusion of urea,UT1(in contrast to its effect on only water permeability in cortical and outer medullary collecting ducts).
4.Because the urea concentration of tubular fluid has been elevated by reabsorption of water in the cortical and outer medullary collecting ducts, a large concentration gradient has been created for urea. In the presence of ADH, the inner medullary collecting ducts can transport urea, and urea diffuses down its concentration gradient into the interstitial fluid. Urea that would have otherwise been excreted is recycled into the inner medulla, where it is added to the corticopapillary osmotic gradient.
What is counter current exchange?
The vasa recta participate incountercurrent exchange,which differs from countercurrent multiplication as follows: Countercurrent multiplication, is an active process thatestablishesthe corticopapillary osmotic gradient. Countercurrent exchange is a purely passive process that helpsmaintainthe gradient. The passive properties of the vasa recta are the same as for other capillaries: They are freely permeable to small solutes and water. Blood flow through the vasa recta is slow, and solutes and water can move in and out, allowing for efficient countercurrent exchange.
What are the 3 actions of ADH on the renal tube?
1.When circulating levels of ADH are high, ADH is delivered to the principal cells via the peritubular capillary blood.V2receptorsfor ADH, present in the basolateral membrane, are coupled toadenylyl cyclasevia a stimulatory G protein (Gs).
2.When ADH binds to the receptors, adenylyl cyclase is activated and catalyzes the conversion of ATP tocAMP.
3. and 4.cAMP activatesprotein kinase A.Activated protein kinase A then causesphosphorylationof intracellular structures. The identity of these structures is uncertain, although possibilities include microtubules and microfilaments, which are involved in intracellular shuttling mechanisms.
5. and 6.After the phosphorylation step, vesicles containing water channels are shuttled to and inserted into the luminal membrane of the principal cell, thus increasing its water permeability. The specific water channel that is controlled by ADH isaquaporin 2 (AQP2).Using freeze-fracture electron microscopy, the water channels in the luminal membrane can be visualized in clusters calledintramembranous particles.The presence and number of intramembranous particle clusters correlate with the presence and magnitude of water permeability of principal cells, suggesting that the particle clusters are an anatomic representation of the water channels
What is hyperosmotic urine?
Urine becomes hyperosmotic in the presence of ADH by equilibration of tubular fluid in the collecting ducts with the high osmolarity of the corticopapillary gradient. The corticopapillary osmotic gradient is established by countercurrent multiplication, a function of the loop of Henle, and by urea recycling, a function of the inner medullary collecting ducts.
What is hypoosmotic urine?
Tubular fluid is diluted in the “diluting segments,” which reabsorb NaCl without water. Osmotic equilibration does not occur in the collecting ducts in the absence of ADH, and the dilute urine is excreted.
What are the 3 layers of the filtration barrier?
• Endothelial cells
• Basement membrane- type 4 collagen and heparin sulfate
• Visceral epithelial cells/ podocyte
What is the pathogenesis of glomerular injury?
What are the 5 clinical manifestations of glomerular disease?
How does nephrotic syndrome occur?
How does nephritic syndrome occur?
