Excretory 2

Question 1

One final way to alter GFR is to increase or decrease glomerular surface area (not pressure related)

Answer 1

e.g. mesangial cells around the glomerular capillaries can contract, reducing surface area & thus lowering GFR

Question 2

Tubular reabsorption:

Answer 2

Filtration is largely indiscriminant: includes wastes, nutrients, electrolytes etc. – don’t want to lose all!

More fluid is filtered per day than present in the entire body – clearly don’t want to excrete all this!

So we must return most contents to body  tubular reabsorption

Question 3

Tubular reabsorption is highly selective

Answer 3

Substances we need are reabsorbed while those we don’t are not & thus are excreted in urine

Question 4

transepithelial transport

Answer 4

To be reabsorbed, substances must cross 5 barriers

This entire sequence = transepithelial transport

Question 5

Reabsorption can be passive or active

Answer 5

There are many substances that are reabsorbed: vitamins, some hormones, electrolytes (Ca2+, Mg2+, HCO3-, etc.), & other nutrients

We’ll focus only on Na+ (passive & active), H2O (passive), glucose (active), & amino acids (active)

Remember: most reabsorption happens from proximal tubule, but some from LoH & distal tubule as well

Question 6

Na+ reabsorption:

Answer 6

~80% of total energy used in the kidneys is for Na+ transport, highlighting its importance

Na+ is reabsorbed in all parts of the tubule except the descending limb of the LoH (more on this later)

Reabsorption in the proximal tubule (~67%) plays a pivotal role in reabsorption of glucose, amino acids, urea, etc.

Reabsorption in the loop of Henle (~25%) plays a critical role in adjusting osmotic gradients depending on need to conserve or eliminate salt &/or H2O

Reabsorption in the distal tubule (~8%) is important for secretion of K+ & H+

Question 7

Na+ is transported passively & actively

Answer 7

Remember: the Na+/K+ pump actively transports Na+ from cell into ECF/blood

across the basolateral membrane

But movement of Na+ from lumen into tubular cell is passive (down the electrochemical gradient)

across the luminal or apical membrane

Question 8

H2O reabsorption:

Answer 8

Mostly through aquaporins – H2O channels

Remember that H2O movement is always passive

follows salts & other solutes into tubular cells & is further pushed into capillaries due to high conc. of proteins (not filtered through glomerulus)

Question 9

Glucose & amino acid reabsorption:

Answer 9

Movement is through active transport, although the energy required is used indirectly
e.g. Na+/K+ pump moves Na+ out of the tubular cell to ECF, causing Na+ to move from lumen into cell passively
Some Na+ carrier proteins carry glucose with them, even though it’s against conc. gradient
Once pumped into the tubular cell, glucose & amino acids passively diffuse (facilitated diffusion) across basolateral membrane to blood

Question 10

tubular maximum

Answer 10

When all carriers are occupied/saturated, we reach the tubular maximum

the maximum amount of a substance tubular cells can actively transport within a given period of time

Question 11

renal threshold

Answer 11

The point the substance starts being excreted in urine = the renal threshold

e.g. In humans, glucose is maintained in blood ~100mg/100mL – easy to reabsorb all

Renal threshold = ~180mg/100mL

Tubular maximum = ~300mg/100mL

after this, reabsorption is steady & all excess is urinated out

Question 12

Except for urea, waste products are not reabsorbed

Answer 12

As H2O & solutes are reabsorbed, urine becomes concentrated with waste products to be excreted

Because urea is small & easily permeates membranes, & because the conc. gradient becomes so high toward the end of the nephron, some (~40%) is passively reabsorbed & maintained in blood stream

as only a mild toxin, retaining this much is not dangerous

Question 13

Reabsorption of Na+ is subject to hormonal control

Answer 13

The renin-angiotensin-aldosterone system (RAAS) involves a hormonal cascade that helps retain salt & H2O in the body

Remember: the JGA has cells sensitive to BP
“intrarenal baroreceptors”

JGA also has cells that detect Na+ levels

Low Na+ &/or low BP stimulate granular cells of the JGA to secrete the hormone renin

Question 14

aldosterone

Answer 14

Once in blood, renin converts angiotensinogen into angiotensin I, then converted into angiotensin II, which stimulates the adrenal cortex to release the hormone aldosterone

Question 15

Activation of RAAS has 4 consequences:

Answer 15

1. Aldosterone stimulates insertion of additional Na+ channels & Na+/K+ pumps: increases Na+ reabsorption
2. Angiotensin II stimulates vasopressin release – increases H2O retention by increasing aquaporins
3. Angiotensin II causes vaso-constriction, increasing overall blood pressure
4. Angiotensin II stimulates thirst & salt hunger: increasing intake increases blood levels of N+ & H2O

RAAS is a good example of negative feedback

Question 16

Atrial natriuretic peptide (ANP) has opposite effect

Answer 16

ANP is made by the heart & released when cardiac muscle cells are stretched by increased ECF
ANP has several effects, including inhibition of Na+ reabsorption, thus increasing Na+ & H2O excreted in urine

Question 17

Tubular secretion:

Answer 17

Like reabsorption, secretion requires transepithelial transport but moves in reverse

Goal is to excrete unwanted substances that didn’t originally make it into filtrate

Most important substances secreted = H+, K+, & organic ions (e.g. histamine norepinephrine)

Question 18

The extent of H+ secretion depends on acidity of body fluids

Answer 18

e.g. when too acidic, H+ secretion is increased

allows for regulation of acid-base balance

Question 19

K+ is one of the most abundant cations in body but most is intracellular

Answer 19

K+ in ECF must stay very low to allow for proper function of excitable cells

Majority is reabsorbed in proximal tubule, so control of ECF levels is done mostly through secretion (or not) in distal tubule

Question 20

Active K+ movement into tubular cells is coupled with Na+ movement out

Answer 20

K+ reabsorption occurs through K+ channels in basolateral membrane (mostly in proximal tubule)

allows Na/K pump to accomplish Na+ reabsorption with no net effect on K+

K+ secretion occurs through K+ channels in apical membrane (mostly in distal tubule)

Question 21

Both K+ & H+ secretion require exchanges with Na+

Answer 21

This is due to an antiport transporter in distal tubules that exchanges Na+ with either K+ or H+

Thus an increased rate of secretion of one causes a decrease in secretion of the other

in this way, acidosis can = hyperkalemia & vice versa

Question 22

Osmoconcentration

Answer 22

Osmoconcentration = a process that occurs in the renal medulla & involves the loop of Henle, vasa recta, distal tubule, & collecting duct

maintains osmotic pressure (balance of water & salt) to keep body fluids from becoming too diluted or too concentrated

Question 23

The body = isotonic / isosmotic = ~300 mOsm

Answer 23

H2O only moves passively: if kidneys were isotonic like rest of body, we’d only excrete isotonic urine

But H2O levels change regularly so we must be able to excrete dilute or concentrated urine

Fortunately, the renal medulla is not isotonic

Has a vertical osmotic gradient

Question 24

Remember: LoHs of juxtamedullary nephrons plunge into renal medulla along with the vasa recta for each

Answer 24

Each LoH & vasa recta run countercurrent

establish vertical osmotic gradient

Collecting ducts are also located in renal medulla

along with the hormone vasopressin, can produce dilute or concentrated urine

Question 25

The LoH & vasa recta establish the vertical osmotic gradient by medullary countercurrent multiplication

Answer 25

The LoH can be divided into 3 regions with different properties

1. the descending limb is highly permeable to H2O but does not actively transport Na+
2. the hairpin turn region & thin portion of the ascending limb is not permeable to H2O & does not actively transport Na+
3. the thick ascending limb actively transports NaCl out but is not permeable to H2O, so it cannot leave despite the osmotic pressure

Question 26

Countercurrent exchange with the vasa recta preserves the vertical osmotic gradient

Answer 26

The renal medulla must be supplied with blood, but capillaries are permeable to NaCl & H2O

blood traveling through medulla would progressively pick up salt & lose H2O, negating the kidney’s efforts

This dilemma is avoided by the hairpin shape of vasa recta, looping back through the gradient in reverse

H2O & NaCl are exchanged, but by the time the vasa recta leaves through the top of the medulla, it is back to isotonic (like the top of the renal medulla)

This passive exchange between the vasa recta & interstitial fluid = countercurrent exchange

Question 27

Benefits of countercurrent multiplication

Answer 27

1. hypotonic fluid can leave the nephrons, allowing for dilute urine
2. the established gradient allows the distal tubule & collecting ducts (+ vasopressin) to concentrate the urine so that it is hypertonic (to retain H2O)

Question 28

After leaving the LoH, the remaining fluid (at ~100 mOsm) passes through distal tubule & collecting duct

Answer 28

H2O is driven to leave: whether it does so or not is dictated by how many aquaporins are present

Aquaporins are only inserted when the hormone vasopressin is present

Question 29

Remember: vasopressin (“ADH”) is produced by the hypothalamus & released by the posterior pituitary

Answer 29

Osmoreceptors in the hypothalamus detect H2O levels:

if high, vasopressin is inhibited

if low, vasopressin is released

Question 30

Vasopressin stimulates insertion & maintenance of aquaporins specifically in the apical membranes of distal tubules & collecting ducts

Answer 30

Allows H2O to be reabsorbed instead of secreted

Question 31

The steep osmotic gradient is what allows enough H2O to be reabsorbed

Answer 31

very useful in times of dehydration

The osmotic gradient also allows for more dilute urine to be excreted

In both cases excretion of wastes & other urinary solutes can remain constant

Question 32

If H2O moves out of collecting duct into interstitial space when vasopressin is present, why doesn’t it dilute the vertical osmotic gradient?

Answer 32

It is quickly picked up by surrounding capillaries & returned to the vascular system moving away from kidneys

Question 33

One last player during osmoconcentration: urea

Answer 33

The concentration of urea is far higher in the collecting duct than in the interstitial fluid

If urea can’t leave, it can oppose / inhibit H2O reabsorption through collecting duct aquaporins

“urea recycling” prevents urea- related water loss

diffuses into out & some enters the LoH – hence “recycling”

Question 34

The mammalian bladder wall consists of smooth muscle & specialized epithelial cells

Answer 34

The bladder muscle can stretch a huge amount without a buildup in tension

The highly folded bladder wall flattens during filling to increase capacity

Question 35

Micturition

Answer 35

= urination, the process of bladder emptying

Governed by 2 mechanisms: reflex & voluntary

Stretch receptors also send signals to brain, producing “urge” to urinate

Voluntary overrides reflex, but not indefinitely

Question 36

Because it is so crucial to clear wastes & maintain osmotic balance, kidney problems can be extremely dangerous

Answer 36

Unfortunately these are common: renal failure is the 9th leading cause of death in the US

e.g. excessive glucose in urine of people with diabetes causes damage

Question 37

Obstruction is especially common in domestic cats

Answer 37

Cats are desert animals that produce highly concentrated & also highly acidic urine due to diet high in meat & low in water

Problems occur in domestic cats fed food that doesn’t match natural diets (high fat, high carbs, non-muscle protein)

Urine is much less acidic, causing urinary crystals to form: can block or damage urethra or bladder

especially common in male cats