Tubular processing of glomerular filtrate Flashcards
What are the 3 basic renal processes that represent all the substances in the urine?
- glomerular filtration
- tubular reabsorption
- tubular secretion
Is tubular reabsorption passive or selective?
Highly selective!!
The glomerular filtrate that is presented to the tubules is basically ______
Plasma, without the protein or anything bound to protein
- need to consider when administering drugs that are bound to protein
Calcium is bound to ____
Albumin
- filtrate should contain half the concentration of total calcium or the same amount as ionized/unbound calcium
Carrier mediated reabsorption process
Too many solutes presented to be reabsorbed will cause carrier proteins to become saturated and any more solute will pass on and fail to be reabsorbed
What are 4 main substances that are usually reabsorbed 100%?
- glucose
- amino acids
- protein
- bicarb (>99.9%)
What is 1 substance that is never reabsorbed?
Creatinine
Why is urea reabsorbed 50% of the time if it is a waste product?
To increase tonicity of the medulla to allow for reabsorption of water
Route of transport for tubular reabsorption
- across tubular epithelial membranes
- into renal interstitial fluid
- through the peritubular capillary membrane back into the blood
How are water and solutes transported?
- transcellular: thought the cell membrane
- paracellular: through spaces between the cell junctions
Substances are diffused through the peritubular capillary walls into the blood by what 3 forces?
- hydrostatic
- colloidal
- osmotic
- Starlings forces*
Active transport
Moves a solute against an electrochemical gradient and requires energy derived from metabolism
Primary active transport
Transport that is coupled directly to an energy source
- ex: sodium-potassium ATPase pump
Secondary active transport
Transport that is coupled indirectly to an energy source
- ex: reabsorption of glucose due to an ion gradient
Osmosis
Reabsorption of water by a passive physical mechanism, from a region of low solute concentration to high solute concentration
In the proximal tubules, water passage is relatively ______
Unobstructed
- compare to controlled passage in the distal tubules and collecting ducts
What are the 4 primary known active pumps?
- Na K ATPase (provides electrochemical gradient for secondary active facilitated uptake of other substances)
- Ca ATPase
- H ATPase
- H K ATPase
Ultrafiltration
Bulk flow
- passive method of transporting solutes thru the peritubular capillary walls into the blood
- mediated by hydrostatic and colloid osmotic forces
Is reabsorption of sodium primary or secondary active transport?
Primary
- utilizes an electrochemical gradient (Na-K ATPase)
Where is the Na-K ATPase pump located within the cell?
On the basolateral side
- uses released energy from hydrolysis of ATP to transport sodium ions out of the cell and into the interstitum
Where does sodium diffuse to once it is in the interstitium?
Could go into the peritubular capillary and into the blood, or it could diffuse back into the tubular lumen
Why would sodium move back into the tubular lumen?
Ensures that there is always sodium available to provide substrate for the cotransport of molecules and prevents excessive sodium resorption in times of excessive sodium consumption
There is a ____ concentration of sodium and a ____ concentration of potassium inside the cell
Low; high
- creates a negative charge of -70 millivolts
What is located on the apical side of the proximal tubular epithelial cells to facilitate diffusion?
- brush border
- channels
- molecules/ligands to bind both sodium and another solute (glucose, amino acids, etc)
What are the 3 steps of sodium transport from the tubular lumen into the blood?
- Na diffuses across apical membrane into cell DOWN an electrochemical gradient
- Na is transported across basolateral membrane AGAINST an electrochemical gradient
- Na, water, etc are reabsorbed from intestinal fluid into peritubular capillaries by ultrafiltration
How are proteins reabsorbed due to their large size?
Attach to specific receptor molecules on tubular epithelial cell membrane and are invaginated internally into the cell
–> pinocytosis
What are the requirements of pinocytosis?
- tubulin polymerization
- small changes in cytoskeleton
- both require energy, so pinocytosis is another form of active transport!!*
In secondary active transport _____ interacts with _____ and are transported together across the membrane
2 (or more) substances; specific membrane protein (carrier)
- requires a specialized carrier molecule designed to fit both transported molecules
- BOTH molecules need to be present and bound to carrier for it to work
Does secondary active transport require energy directly from ATP?
No, utilizes electrochemical gradient created by simultaneous facilitated diffusion of another transported substance (usually sodium)
Glucose and amino acids are transported into the cell ______ the electrochemical gradient and are diffused across the basolateral membrane by _______
Against; facilitated diffusion due to concentration gradient inside the cell
Sodium glucose co-transporters
Located on brush border of apical membrane, carry glucose into cell against concentration gradient
- SGLT2, SGLT1
Glucose transporters
Located on the basolateral membrane, diffuses glucose out of the cell into the interstitial spaces (expends no energy)
- GLUT2, GLUT1
A substance is said to undergo “active” transport when ______
At least one of the steps in reabsorption involves primary or secondary active transport, even though other steps in the reabsorption process may be passive
Counter-transport
Electrochemical gradient created by Na-K ATPase pump provides energy needed to eliminate unwanted substances (hydrogen) from the cell, into the tubular lumen
Transport maximum
Limit to the rate at which the solute can be transported
- glucose
- amino acids
- protein
Why doesn’t sodium exhibit a maximum transport rate?
There are so many avenues through which sodium can move
When does glucosuria occur?
When all of the transport proteins are occupied and there is still glucose in the lumen —> glucose will be lost in urine
Excess protein loss could be due to
Glomerulonephritis
- more proteins leak across the glomerulus than the tubules can handle
Tubular disease
- tubules are too injured to handle even a normal protein load
Glucosuria could be the result of what 2 processes?
- hyperglycemia: increased glucose in the blood, causing more glucose to be filtered and presented to the tubules than there are transport molecules for reabsorption
- normoglycemic glucosuria: sick, injured tubular epithelium where there are a diminished number of transport molecules that can’t handle even a normal glucose load
Why does osmotic diuresis occur?
When glucose is left in the tubule, it provides an osmotic effect of holding water in the tubule
= increased urine output, followed by compensatory polydipsia
Different tubules have different _______
Transport maximums
What is another factor that can affect reabsorption?
Time
- if the flow rate of filtrate is so fast that there is insufficient time for reabsorption to occur, then spillage into the urine might occur
Unique features of the proximal tubule
- high cell surface area (brush border)
- high metabolic rate due to high mitochondria amount, leading to high oxygen consumption
- loaded with protein carrier molecules
____of the filtered load of sodium and water is reabsorbed in the proximal tubules
65%
- reabsorbs essentially all glucose and amino acids
Why is the secretion of hydrogen ions into the tubular lumen important?
Is an important step in reabsorption of bicarb from tubule
- combines H with HCO3 to form H2CO3, which dissociates into H2O and CO2
In the first half of the proximal tubule, sodium is reabsorbed by co-transport with ______
Glucose, amino acids, other solutes
- preferred
In the second half of the proximal tubule, sodium is reabsorbed by co-transport with_____
Chloride
- higher chloride concentration favors diffusion from lumen through intercellular junctions into the renal interstitial fluid
Why does the total solute concentration remain the same all along the proximal tubule?
Due to extremely high permeability of the proximal tubule to water
Proximal tubule is an important site for secretion of _____
Organic acids and bases, and drugs/toxins
As solutes are absorbed, the filtrate becomes more _____, while the solutes in the interstitum become more _____
Dilute; concentrated
flow of solutes always favors movement into the capillary
Solvent drag
As water flow, some of the things dissolved in water flow with it
Concentration of solutes that are not absorbed _____ as water flows
Increases
- if the tubule is permeable, they will move down their own concentration gradient back into circulation
- if tubule is impermeable, then the concentration will continue to increase
In the proximal tubule, passive reabsorption of chloride occurs due to
- changes in electrical and concentration gradient
- secondary active reabsorption via Na-Cl cotransport molecule
How is urea passively reabsorbed?
Urea is a non-polar, lipid soluble compound so as water is reabsorbed, the urea concentration increases in the tubule lumen and some will be passively reabsorbed
Does the concentration of sodium change throughout the proximal tubule?
No, the total amount of Na decreases but the concentration does not due to water moving with Na
While the total solute concentration does not change, the relative ______ does change
Proportion that each solute contributes
Loop of Henle
- no brush border
- thin epithelial membranes
- minimal metabolic activity, with few mitochondria
Thin descending segment
Passive, highly permeable to water
- 20% of water absorption
Why is water absorbed in the thin descending segment at a rate that increases the osmolarity of the urine, when the osmolarity did not increase in the proximal tubule?
Because the interstitial fluid of the renal medulla becomes more hypertonic as it descends
- water moves passively out of the tubule lumen following concentration gradients
The ascending limb (both thin and thick segments) is virtually impermeable to _____
Water
- important for concentrating urine
- all the water that had been reabsorbed from the filtrate in the thin descending limb, causing the filtrate to become more concentrated would move back into the lumen as the tubule exited the hypertonic area of the medulla
The thin ascending loop is moderately permeable to ____
Urea, due to presence of transport molecule facilitating movement of urea into the lumen
- may be slightly permeable to Na
Thick ascending loop
- increased surface area
- increased mitochondria = high metabolic activity
- impermeable to water (even in presence of ADH)
- impermeable to urea
Thick ascending segment accounts for _____ of reabsorption of Na, Cl, and K
25%
- facilitated co-transport system that depends on sodium gradient generated by Na-K ATPase pump on basolateral membrane
- water does not follow!!
Na-K ATPase pump in the thick ascending loop also creates a _____
Negative K ion gradient, allowing K to diffuse across cell membranes back into the tubule lumen
- back diffusion of K creates a slight positive charge pushing other cations to be reabsorbed
Urine becomes more ____ in the thick ascending segment as solutes are absorbed
Dilute
Furosemide blocks the _______, PGE2 down regulates its activity
Sodium - 2 Chloride - Potassium co-transporter on the apical membrane of the thick ascending limb
Prostaglandin E2
Decreases sodium reabsorption at the thick ascending limb of the loop of Henle
- only occurs during dehydration
Administration of NSAIDs ____ sodium reabsorption
Increases, by blocking action of PGE2
- eliminates ability to promote vasodilation to maintain blood flow and delivery of oxygen to renal medulla
Early distal tubule
- goes back into the cortex
- impermeable to water (further dilution)
- impermeable to urea
- active reabsorption of Na, Cl, etc
- functionally similar to thick ascending loop
The early distal tubule contains the _____
Macula densa
- group of closely packed epithelial cells that is a part of the juxtaglomerular complex and provides feedback control of GFR and blood flow to the same nephron
Regulated reabsorption and/or secretion begins in the
Late distal tubule and cortical collecting duct
- everything up until this point has been unregulated
The late distal tubule and collecting duct are impermeable to ___
Urea
Ability of LDT and CT to reabsorb sodium ions and the rate of reabsorption is controlled by _____ and _____
Aldosterone and angiotensin (upregulates Na K pumps)
Principle cells
Secrete potassium from peritubular capillary blood into the tubular lumen
- controlled by aldosterone and concentration of potassium ions in the body fluids
- reabsorb sodium and water from the lumen
Intercalated cells
Type A secrete hydrogen ions by active hydrogen-ATPase
- different from H secretion that occurs in the proximal tubule
- is capable of secreting H ions against a large concentration gradient
- plays a key role in acid-base regulation
Permeability of LDT and CT to water is controlled by
Concentration of ADH
- high levels of ADH cause tubular segments to be permeable to water (dehydration)
- absence of ADH, they are impermeable to water
Principle cells contain ____ on the basolateral membrane and ______ in the apical membrane
Na-K ATPase pumps; Na and K channels
- both are under control of aldosterone, which stimulates activation of operon coding for nuclear transcription of mRNA for production of proteins and enzymes
Diuretics that block action of aldosterone
Decrease activity of Na K ATPase pump and decrease insertion of Na channels into the apical cell membrane
- K sparing
Process of principal cells secreting potassium
- K enters cell due to Na-K ATPase pump, which maintains a high intracellular K concentration
- once inside the cell, K diffuses DOWN its concentration gradient across apical membrane into tubular lumen
Intercalated cells are important for _____
pH control
Intercalated cells utilize ____ and ______
- Na concentration gradient, created by Na K ATPase pump to move H out
- K excreted by principle cells to enable an energy dependent K/H counter transport to pump H out against a larger conc gradient
By exchanging ___ for ___, the intercalated cells are helping prevent the K loss that would have occurred during acidosis
H for K
- also eliminates the H that was the cause of the acidosis
ADH
Causes proteins in the cell to cluster together and fuse into a water channel that is inserted into the cell membrane, making the lipid bilayer of the cell membrane permeable to water
Medullary collecting duct
- H2O permeability controlled by ADH
- permeability to Na and K controlled by aldosterone
- H secretion against a large concentration gradient
Medullary collecting duct is permeable to urea due to
Urea transport molecules that facilitate uptake of urea out of the lumen and into the interstitium (down the concentration gradient)
- helps to raise osmolaltiy
- ADH induces an increase in the number of urea transport molecules
Na reabsorption throughout the tubules
- 65% in the proximal tubule
- 25% in the thick ascending loop of Henle
- 5-7% in the distal tubule
- 5-10% in the collecting tubule
Hormones affecting tubular resorption regulation
- angtiotensin 2
- aldosterone
- ADH
- atrial natiruetic factor
How does angiotensin 2 affect tubular resorption?
- increase efferent arteriole constriction
- increase tubular Na resorption directly
- increase tubular Na resorption via increased aldosterone secretion
Glomerulotubular balance
Ability of certain segments of the nephron (proximal tubule and thick ascending limb) to increase the amount of water and solutes reabsorbed as filtrate flow increase or decreases within physiologic range
Glomerulotubular balance helps prevent _____
Overloading of distal tubular segments when GFR increases
- buffers the effects of spontaneous changes in GFR on urine output
Peritubular physical forces
Balance between hydrostatic and colloidal pressure and concentration gradients across the peritubular capillaries
An increase in resistance of the arterioles _____ peritubular capillary hydrostatic pressure and _____ reabsorption rate
Reduces; increases
Raising the colloid osmotic pressure _____ peritubular capillary reabsorption
Increases
- colloid osmotic pressure is determined by systemic plasma colloid osmotic pressure and filtration fraction
If arterial pressure and/or blood volume increases without any other opposing force ____ increases as well
Renal capillary pressure
Pressure diuresis
More fluid is filtered, less of the filtered fluid is reabsorbed = increases in urinary excretion of sodium and water
Natriuresis occurs due to
Increase in pressure resulting in a down regulation of angiotensin 2 and its effect on sodium resorption directly and mediated thru aldosterone secondarily
A decrease in systemic blood pressure, or CO, or an increase in afferent arteriolar sphincter tone will lead to a ____ in both glomerular and peritubular capillary hydrostatic pressure
Decrease
- decrease in peritubular capillary hydrostatic pressure leads to an increase in absorption = greater absorption of what was filtered
What causes the precursor for angiotensin to be released?
Decreased RBF leads to decreased GFR –> results in slower flow thru the tubule —> allows more time for more Na reabsorption —> stimulates macula densa to produce and release renin
Angiotensin 2 increases ______ and ______
Sodium and water reabsorption
- mediated by increasing multiple cAMP controlled mechanisms of transmembrane Na transport
- stimulates aldosterone secretion
- constricts efferent arteriole
Aldosterone increases _____ and _____
Sodium reabsorption and potassium secretion
- stimulates Na K ATPase pump and increase Na permeability on the apical membrane
What is the primary site of action for aldosterone?
Principle cells of the cortical collecting tubule
ADH increases _____
Water reabsorption
Inappropriate secretion of ADH results in _____
Hyponatremia
Atrial natriuretic hormone decreases ____ and _____
Sodium and water reabsorption
Atrial natriuretic peptide is secreted when
Atria become distended due to increases water absorption, leading to blood volume expansion
- ANF blocks Na resorption in the collecting ducts
