Excretory 2 Flashcards
One final way to alter GFR is to increase or decrease glomerular surface area (not pressure related)
e.g. mesangial cells around the glomerular capillaries can contract, reducing surface area & thus lowering GFR
Tubular reabsorption:
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
Tubular reabsorption is highly selective
Substances we need are reabsorbed while those we don’t are not & thus are excreted in urine
transepithelial transport
To be reabsorbed, substances must cross 5 barriers
This entire sequence = transepithelial transport
Reabsorption can be passive or active
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
Na+ reabsorption:
~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+
Na+ is transported passively & actively
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
H2O reabsorption:
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)
Glucose & amino acid reabsorption:
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
tubular maximum
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
renal threshold
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
Except for urea, waste products are not reabsorbed
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
Reabsorption of Na+ is subject to hormonal control
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
aldosterone
Once in blood, renin converts angiotensinogen into angiotensin I, then converted into angiotensin II, which stimulates the adrenal cortex to release the hormone aldosterone
Activation of RAAS has 4 consequences:
- Aldosterone stimulates insertion of additional Na+ channels & Na+/K+ pumps: increases Na+ reabsorption
- Angiotensin II stimulates vasopressin release – increases H2O retention by increasing aquaporins
- Angiotensin II causes vaso-constriction, increasing overall blood pressure
- Angiotensin II stimulates thirst & salt hunger: increasing intake increases blood levels of N+ & H2O
RAAS is a good example of negative feedback
Atrial natriuretic peptide (ANP) has opposite effect
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
Tubular secretion:
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)
The extent of H+ secretion depends on acidity of body fluids
e.g. when too acidic, H+ secretion is increased
allows for regulation of acid-base balance
K+ is one of the most abundant cations in body but most is intracellular
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
Active K+ movement into tubular cells is coupled with Na+ movement out
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)
Both K+ & H+ secretion require exchanges with Na+
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
Osmoconcentration
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
The body = isotonic / isosmotic = ~300 mOsm
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
Remember: LoHs of juxtamedullary nephrons plunge into renal medulla along with the vasa recta for each
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
The LoH & vasa recta establish the vertical osmotic gradient by medullary countercurrent multiplication
The LoH can be divided into 3 regions with different properties
- the descending limb is highly permeable to H2O but does not actively transport Na+
- the hairpin turn region & thin portion of the ascending limb is not permeable to H2O & does not actively transport Na+
- the thick ascending limb actively transports NaCl out but is not permeable to H2O, so it cannot leave despite the osmotic pressure
Countercurrent exchange with the vasa recta preserves the vertical osmotic gradient
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
Benefits of countercurrent multiplication
- hypotonic fluid can leave the nephrons, allowing for dilute urine
- the established gradient allows the distal tubule & collecting ducts (+ vasopressin) to concentrate the urine so that it is hypertonic (to retain H2O)
After leaving the LoH, the remaining fluid (at ~100 mOsm) passes through distal tubule & collecting duct
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
Remember: vasopressin (“ADH”) is produced by the hypothalamus & released by the posterior pituitary
Osmoreceptors in the hypothalamus detect H2O levels:
if high, vasopressin is inhibited
if low, vasopressin is released
Vasopressin stimulates insertion & maintenance of aquaporins specifically in the apical membranes of distal tubules & collecting ducts
Allows H2O to be reabsorbed instead of secreted
The steep osmotic gradient is what allows enough H2O to be reabsorbed
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
If H2O moves out of collecting duct into interstitial space when vasopressin is present, why doesn’t it dilute the vertical osmotic gradient?
It is quickly picked up by surrounding capillaries & returned to the vascular system moving away from kidneys
One last player during osmoconcentration: urea
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”
The mammalian bladder wall consists of smooth muscle & specialized epithelial cells
The bladder muscle can stretch a huge amount without a buildup in tension
The highly folded bladder wall flattens during filling to increase capacity
Micturition
= 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
Because it is so crucial to clear wastes & maintain osmotic balance, kidney problems can be extremely dangerous
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
Obstruction is especially common in domestic cats
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
