Module 4 Section 4

Question 1

tubular reabsorption

Answer 1

• the glomerular filtrate that enters the tubules is identical to plasma with the exception of plasma proteins
• there is no selectivity to glomerular filtration
• tubular reabsorption includes the processes by which water and other necessary solutes are returned to the plasma, while allowing waste products to remain in the filtrate

Question 2

tubular reabsorption - step 1

Answer 2

reabsorption begins with either active or passive movement of substances from the tubule into the interstitial space

Question 3

tubular reabsorption - step 2

Answer 3

reabsorption then continues with passive movement of substances from the interstitial space back into the blood stream

Question 4

fate of various substances reabsorbed by the kidneys

Answer 4

• unlike glomerular filtration, tubular reabsorption is highly selective and variable
• the tubules have a high reabsorptive capacity for substances needed by the body, and a low reabsorptive capacity for substances not needed by the body
• since water and solutes are critical for maintaining homeostasis, their tubular reabsorption is high

Question 5

transepithelial transport

Answer 5

• the area of the epithelial cells that are in contact with the tubule lumen is the luminal membrane, and the area of the epithelial cells that are in contact with the interstitial fluid is the basolateral membrane
• transepithelial transport (transcellular transport) is defined as the movement of solutes across an epithelial cell layer through the cells

Question 6

membranes from neighbouring epithelial cells

Answer 6

• they are not in contact, other than where there are tight junctions connecting them
• because of this, any substance that enters an epithelial cell cannot transport it to a neighbouring cell, the substance must move through the cell into the interstitial space

Question 7

transepithelial transport - step 1

Answer 7

the substance must cross the luminal membrane

Question 8

transepithelial transport - step 2

Answer 8

the substance must pass through the cytosol

Question 9

transepithelial transport - step 3

Answer 9

the substance must cross the basolateral membrane

Question 10

transepithelial transport - step 4

Answer 10

it must diffuse through the interstital fluid

Question 11

transepithelial transport - step 5

Answer 11

it must cross the capillary wall to enter the plasma

Question 12

locations of Na+ reabsoprtion

Answer 12

• since 99.5% of all filtered Na+ is reabsorbed, this process is highly controlled
• unlike most solutes, Na+ can be reabsorbed to various extents along the entire tubule
• the reason why Na+ is reabsorbed in so many places is that it is critical to the reabsorption of many other substances

Question 13

locations of Na+ reabsorption within the kidney

Answer 13

1. proximal tubule
2. ascending limb of the loop of Henle
3. distal collecting tubules

Question 14

proximal tubule

Answer 14

• 76% of Na+ is reabsorbed
• reabsorption of Na+ in this segment of the nephron is needed for the reabsorption of glucose, amino acids, water, Cl-, and urea

Question 15

ascending limb of the loop of henle

Answer 15

• loop of henle absorbs 25% of the total reabsorbed Na+
• int he ascending limb of the loop of henle, Na+ along with Cl- are essential to either concentrate, or dilute, the urine depending upon bodys needs

Question 16

distal and collecting ducts

Answer 16

• distal and collecting tubules collecitvely reabsorb 8% Na+
• it is here that Na+ reabsorption is under hormonal control and plays a key role in regulating ECF volume and secretion of both K+ and H+

Question 17

active transport of Na+

Answer 17

• the reabsorption of Na+ is both active and passive
• Na+ moves passivley across the limunal membrane, but the movement of Na+ across the basolateral membrane is by active transport involving Na+-K+ ATPase pump
• due to large volume of Na+ that is reabsorbed, its transport accounts for 80% of the energy needs of the kidney
• by actively transporting Na+ into the interstitial fluid, it helps to keep the cytosol Na+ concnetration low to allow for the passive difffusion across the luminal membrane

Question 18

passive transport of Na+

Answer 18

the mechanism of passive transport of Na+ across the luminal membrane varies throughout the various segments of the tubule

Question 19

passive transport of Na+ in the proximal tubule

Answer 19

• Na+ crosses by a cotransporter carrier that simulatneously moves organic nutrients, such as glucose and amino acids
• these nutrients are transferred by secondary active transport, as they use the concnetration gradient of Na+ established by the Na+-K+ ATPase pump to be transported against their concentration gradient, along with the passive transport of Na+

Question 20

passive transport of Na+ in the collecting duct

Answer 20

Na+ passively enters the epithelial cells through a Na+ channel

Question 21

hormonal regulation of Na+

Answer 21

• in the proximal tubule and the loop of henle, a constrast percentage of the filtered Na+ is reabsorbed regardless of the total amount of Na+ within the body fluids
• in the distal tubule, the reabsorption of a small percentage of the filtered Na+ is subject to hormonal control
• most important hormonal system involved in regulation of Na+ is the renin-angiotensin-aldesterone system (RAAS)
• within the juxtaglomerular apparatus, there are granular cells that secrete renin into the blood

Question 22

3 primary triggers of renin secretion

Answer 22

1. when the glomerular cells detect a drop in blood pressure, they secrete renin
2. the granular cells are innervated by the sympathetic nervous system and will release renin when sympathetic activity increases
3. the mascula densa cells in the tubular portion of the juxtaglomerular apparatus are sensitive to the Na+ and whne there is a decrease in luminal Na+, the lacula densa cells trigger the granular cells to secrete renin

Question 23

renin and Na+

Answer 23

once renin has been secreted inot the blood, a series of events occur to regulate Na+ within the blood

Question 24

explain this image

Answer 24

• renin: once secreted, renin acts like an enzyme to convert angiotensinogen into angiotnesin I
• angiotensin-converting enzyme: when circulating angiotensin I passes through the lungs, it is converted to angiotensin II by the enzyme angiotensin converting enzyme (ACE)
• angiotensin II: stimulates the adrenal cortex to release aldosterone
• aldosterone: causes an increase in Na+ reabsorption in the distal and collecting tubules

Question 25

actions of aldosterone

Answer 25

- under the influence of aldosterone, tubular epithelial cells increase the insertion of Na+ channels in the luminal membrane and Na+-K+-ATPase carriers in the basolateral membrane - this results in a greater passive flow of Na+ out of the tubular fluid - this enhanced Na+ retention also causes increased water retention and will therefore increase arterial blood pressure

Question 26

atrial natriuretic peptide (ANP)

Answer 26

- ANP is another hormone involved in the regulation of Na+ and water - its actions are opposite to those of aldosterone in that ANP release reduces Na+ load and blood pressure - when blood volume increase, or there is an increase in venous return, stretch receptors in the left atrium, aortic arch, and carotid sinus stimulate the release of ANP

Question 27

3 main actions of ANP

Answer 27

1. directly inhibits Na+ reabsorption in the distal tubules so there is more Na+ excreted in the urine 2. inhibits both renin and aldosterone secretion 3. dilates the afferent arterioles and increases GFR. as more salt water are filtered, more salt and water are excreted

Question 28

active reabsorption of tubular/transport maximum

Answer 28

- any substance that is actively reabsorbed will bind to a specific carrier protein in the plasma membrane - because there are a limited number of carrier proteins in a membrane, there is a limit to how much of a substance can be reabsorbed - this is designated as the tubular or transport maximum (Tm)

Question 29

tubular/ transport maximum

Answer 29

- for any given substance, if its concnetration in the tubular fluid exceed its Tm, then the excess will be excreted in the urine - the plasma concentration at which the Tm is exceeded is called the renal threshold - the plasma concetration of many substances are essential regulated by the kidneys and this carrier-mediated limitation

Question 30

phosphate and the kidneys

Answer 30

- for many electrolytes, such as phsophate and calcium, the kidneys help to regulate their plasma conc - regulation of the plasma conc of phosphate within the kidney is achieved becasue the renal threshold for phosphate is the same as the normal plasma conc of phosphate - since our diets are very rich in phosphate, after eating there is a rise in plasma conc of phosphate - this increases the filtered load of phosphate but since the maximum for reabsorption is the same as the plasma conc all phsophate above the normal plasma conc is excreted in urine - this restores plasma phosphate concentration to normal

Question 31

reabsorption of phosphate and calcium

Answer 31

- unlike the reabsorption of organic nutrients like glucose and amino acids, reabsorption of phosphate and calcium are under hormonal control - hormones can alter their renal thresholds to modulate their reabsorption to match the bodys needs

Question 32

hormonal control of phosphate

Answer 32

- PTH can alter the renal thresholds for phosphate and calcium and can adjust the quantity of conserved electrolytes, depending on the bodys needs - a fall in plasma concentration results in two effects which help raise the circulating level back to normal

Question 33

2 effects caused by a fall in plasma phosphate concentration - effect 1

Answer 33

- because of inverse relationship between the phosphate and calcium concentrations in the plasma, a fall in plasma phosphate increases plasma calcium, which directly suppresses PTH secretion - in the presence of reduced PTH, phosphate reabsorption by the kidneys increases, returning plasma phosphate concentration toward normal

Question 34

2 effects caused by a fall in plasma phosphate concentration - effect 2

Answer 34

a fall in plasma also increases activation of vitamin D within the kidney, which then promotes absorption in the intestine

Question 35

glucose and the kidneys

Answer 35

- glucose plasma concentrations are not regulated by the kidneys - the plasma concetration of glucose is normally 100mg per 100ml of plasma - glucose is also small enough that it is freely filterbale and the concetration in Bowmans capsule filtrate is the same as it is in the plasma - given that the normal GFR is 125 ml/min, we can calculate that 125 mg/min glucose is filtered - this is called the filtered load of a substance and is calculated as filtered load = plasma concentration x GFR - any increase in GFR results in a proportional icnrease in its filtered load

Question 36

at what plasma concetration will glucose start appearing in the urine

Answer 36

- its normal Tm is 375 mg/min - this means that for all filtered loads of glucose below 375 mg/min, 100% of the glucose will be reabsorbed - only when the filtered load of glucose exceeds 375 mg/min will glucose appear in the urine

Question 37

why does diabetes mellitus cause increased glucose levels in the blood that cause increase levels in the urine

Answer 37

- urine contains no glucose because the kidneys are able to reabsorb it - bowmans capsule collects the filtrate that the glomerulus forms which includes urea, electrolytes, and glucose - the filtrate then passes into the proximal tubule to be reabsorbed - proximal tubule, can only reabsorb a limited amount of glucose - when blood glucose levels exceed 300mg/100mL, the proximal tubule is overhwelmed and begins to excrete glucose into the urine

Question 38

water

Answer 38

- water is passivley reabsorbed all along the tubule as it follows sodium - proximal tubule: 65%, loop of henle: 15%, distal and collecting tubules: 20% - the fraction of water reabsorbed in the proximal tubule and loop of henle is constant, despite the sodium and water load in the body - the proportion of water reabsorbed in the distal tubule and collecting tubule can vary depending on hormonal influences and the hydration state of the body - water flows through water channels called aquaporins - those in the proximal tubule are always open allowing the flow of water by osmosis - those in the distal tubule are under control by vasopressin, so they are not always open - sodium alone doesnt product the osmotic dirivng forces to bring water from the peritubular capillaries - the plasma-colloid oncotic pressure of the peritubular capillaries also produces a strong osmotic drive for water reabsorption

Question 39

chloride

Answer 39

- despite the high concnetration of chloride in the plasma, the kidneys do not directly regulate it - the majority of chloride does not undergo transepithelial transport, rather it leaves the tubular fluid by moving between the epithelial cells - it goes down its electrochemical gradient, essentially following the amount of Na+ reabsorption - the amount of chloride reabsorbed is determined by the amount of sodium reabsorbed

Question 40

urea

Answer 40

- though urea is a waste product from the breakdown of protein, a large amount of urea is reabsorbed - the concentratio of urea at the beginning of the proximal tubule is the same as the plasma concentration of urea so there is no net diffusion - as fluid moves through the promixal tubule, its volume is reduced by 2/3 as water is reabsorbed so the tubular concnetration of urea increases 3-fold making it passively reabsorbed - with each pass through the nephron, only 40-50% of plasma urea is filtered and excreted from the body - blood urea, measured as blood urea nitrogen (BUN), has historicall been used as a measure of renal failure - during renal failure, less urea is excreted so it accumulates in the plasma and can clinically measured