AP 18 Nov 24 Lecture 31 Flashcards
How is renal plasma flow determined using PAH?
Renal plasma flow is determined by measuring the clearance of PAH (para-aminohippuric acid) and involves comparing venous and arterial concentrations of PAH.
What percentage of PAH is typically removed by the kidneys?
The kidneys can remove about 90% of PAH as blood passes through them.
What role does the macula densa play in regulating GFR?
The macula densa helps adjust or auto-regulate GFR through the release of renin and nitric oxide, affecting the resistance of afferent and efferent arterioles.
How does angiotensin II affect the arterioles?
Angiotensin II preferentially constricts the efferent arteriole while causing relaxation of the afferent arteriole, leading to a reduction in afferent resistance.
What is the effect of drugs that relax blood vessels on GFR?
Drugs that relax blood vessels, such as calcium channel blockers and nitric oxide donors, typically preferentially affect the afferent arteriole, which can increase GFR.
What happens to sodium reabsorption in the proximal tubule when angiotensin II binds to its receptors?
Angiotensin II binding increases the activity of sodium-potassium ATPase pumps in the proximal tubule, enhancing sodium reabsorption.
How is bicarbonate reabsorbed in the proximal tubule?
Bicarbonate is reabsorbed in the proximal tubule primarily through a sodium-bicarbonate symporter, which moves sodium and bicarbonate out of the cell simultaneously.
What is bulk flow in the context of renal physiology?
Bulk flow refers to the process of reabsorption in the peritubular capillaries, driven by capillary forces, allowing for significant reabsorption of fluids and solutes.
What is the role of urea in the renal interstitium?
Urea helps create a concentrated renal interstitium, facilitating water reabsorption via osmosis.
What are the two pathways for reabsorption in the proximal tubule?
Reabsorption occurs through paracellular pathways (between cells) and transcellular pathways (through cell membranes).
What is the role of the renal interstitium in water retention?
The renal interstitium helps hold on to as much water as possible by packing solids to assist with osmosis.
What are the pathways involved in substance movement in the kidneys?
Substance movement in the kidneys occurs via transcellular pathways, passive diffusion, and paracellular pathways.
What is the function of the brush border in proximal tubular cells?
The brush border increases the surface area of proximal tubular cells by about 20 fold, allowing for more transporters to be placed for reabsorption.
How does sodium move into proximal tubular cells?
Sodium moves into proximal tubular cells via an electrochemical gradient, which involves both concentration and electrical gradients.
What is the typical membrane potential in the kidney?
The typical membrane potential in the kidney is around negative 70 mV.
What happens to chloride concentration in the proximal tubule?
Chloride concentration tends to increase slightly as it follows sodium reabsorption, especially in the second half of the proximal tubule.
What is the role of the proximal tubule in protein reabsorption?
The proximal tubule reabsorbs about 1.7 grams of the 1.8 grams of protein filtered daily, using endocytosis to manage small amounts of filtered proteins.
What is endocytosis in the context of proximal tubular cells?
Endocytosis is the process by which proximal tubular cells engulf filtered proteins, breaking them down into amino acids for reabsorption.
How does the proximal tubule regulate acid-base balance?
The proximal tubule regulates acid-base balance primarily through the sodium-proton exchanger, which secretes protons and reabsorbs sodium.
What is the role of carbonic anhydrase in the proximal tubule?
Carbonic anhydrase facilitates the conversion of carbonic acid into carbon dioxide and water, aiding in bicarbonate reabsorption and pH regulation.
What is formed in the proximal tubule?
A bunch of carbonic acid is formed in the proximal tubule.
What role does carbonic anhydrase play in the proximal tubule?
Carbonic anhydrase speeds up the reaction of carbonic acid dissociating into CO2 and water.
What happens if the reaction of carbonic acid goes in the opposite direction?
Carbonic acid can dissociate into protons and bicarbonate.
What is the effect of carbonic anhydrase inhibitors?
They slow down the proton-sodium exchanger, leading to decreased bicarbonate reabsorption and potential acidosis.
What is the function of glutamine in the proximal tubule?
Glutamine is converted into bicarbonate and ammonium, helping to balance acid-base status.
How is bicarbonate produced in the proximal tubule?
One glucose molecule is converted into two bicarbonate molecules and two ammonium molecules.
What is the role of sodium phosphate in urine?
Sodium phosphate acts as a buffer for protons in urine.
How is calcium reabsorbed in the proximal tubule?
Calcium is reabsorbed through paracellular and transcellular pathways, often dragged along with water.
What regulates calcium levels in the body?
The parathyroid gland monitors calcium levels and releases parathyroid hormone (PTH) when levels are low.
What are the effects of parathyroid hormone (PTH)?
PTH increases calcium reabsorption in the kidneys, activates vitamin D3 for dietary absorption, and stimulates bone breakdown.
What happens to bone density during chronic hypocalcemia?
Chronic hypocalcemia can lead to osteoporosis due to increased bone breakdown and decreased bone building.
What are osteoblasts?
Osteoblasts are bone builders that increase bone density by taking calcium and phosphate and forming bone.
What happens if there is a calcium deficit?
Bone building activity by osteoblasts is inhibited while bone breakdown is stimulated.
What is the role of PTH?
PTH increases osteoclast activity (bone breakdown) and decreases osteoblast activity (bone building).
What happens to PTH levels when calcium levels are high?
PTH levels should be low, leading to reduced osteoclast activity and increased osteoblast activity.
How can we rebuild bones?
Taking calcium supplements can help reinforce bones, provided calcium is reabsorbed.
What happens with long-term calcium deficit?
It can lead to porous bones that are more likely to fracture.
What is the function of the proximal tubule?
The proximal tubule secretes organic compounds and is involved in the reabsorption of substances.
What are the two basic categories of organic compounds handled by the kidney?
Organic cations and organic anions.
What are examples of endogenous organic anions?
Bile salts, purates, urate, oxalate.
What are examples of exogenous organic anions?
Drugs such as penicillin and salicylates.
What are examples of endogenous organic cations?
Acetylcholine, creatine, dopamine, epinephrine.
What are examples of exogenous organic cations?
Isoproterenol, atropine, morphine, quinine.
How are organic cations removed from the proximal tubule?
Via a proton-dependent antiporter system.
How are organic anions removed from the proximal tubule?
Via a sodium-dependent process involving alpha-ketoglutarate.
What is the significance of alpha-ketoglutarate in organic anion transport?
It helps concentrate in proximal tubular cells and facilitates the exchange with organic anions.
What is the general rule of thumb for reabsorption in the proximal tubule?
About two-thirds of most substances are reabsorbed in the proximal tubule.
What is the loop of Henle?
A U-shaped loop in the nephron that consists of descending and ascending limbs.
What occurs in the thin descending limb of the loop of Henle?
Water is reabsorbed as tubular fluid moves into a more concentrated environment.
What occurs in the thin ascending limb of the loop of Henle?
It is relatively impermeable to water and primarily reabsorbs sodium and chloride.
What is the permeability of the thin ascending limb of the loop of Henle?
The thin ascending limb of the loop of Henle is relatively impermeable to water.
What transporter is present in the thin ascending limb of the loop of Henle?
A sodium chloride transporter reabsorbs sodium and chloride from the tubular fluid.
What type of transporter is the sodium chloride transporter in the thin ascending limb?
It is a primary active transporter driven by ATP.
What happens to the ascending limb of the loop of Henle as it widens?
It becomes the thick ascending limb, which is still relatively impermeable to water.
What ions are reabsorbed in the thick ascending limb of the loop of Henle?
Magnesium and calcium are reabsorbed via a paracellular route.
What role does potassium play in the reabsorption of magnesium and calcium?
Potassium channels allow potassium to leak back into the tubular fluid, creating a positive charge that helps push magnesium and calcium to be reabsorbed.
What is the electrical charge in the tubular fluid at the thick ascending limb?
The charge is positive 8 millivolts, which aids in the reabsorption of divalent cations.
What is the function of sodium-potassium pumps in the thick ascending limb?
They help maintain acid-base balance and facilitate ion transport.
What is the significance of loop diuretics?
Loop diuretics inhibit the transporter in the thick ascending limb, reducing the concentration of the renal interstitium.
What is the maximum osmolarity of the renal interstitium?
The maximum osmolarity is about 1200 mOsm/L, which reflects the kidney’s ability to conserve water.
What hormone influences calcium reabsorption in the distal tubule?
Parathyroid hormone (PTH) increases the number of calcium channels in the distal tubule.
What type of diuretics affect calcium reabsorption in the distal tubule?
Thiazide diuretics inhibit sodium and chloride reabsorption in the distal tubule.
What cells in the distal tubule are sensitive to aldosterone?
Principal cells are sensitive to aldosterone and influence sodium reabsorption and potassium secretion.
How does aldosterone affect potassium and sodium in the distal tubule?
Aldosterone speeds up potassium secretion into the tubule and increases sodium reabsorption.
Cellular extensions on the tubular lumen side that increase surface area and allow for more efficient/increased amount of transporters.
Brush Borders
What is the charge inside the tubular epithelial cells?
Intercellular space charge is -70mV
What is the charge within the tubular lumen (Lecture references PCT)
PCT charge is -3mV
What is significant about Cl- transport in the PCT?
There is a Cl- time lag as it follows Na+ since there are no dedicated transporters in the PCT
Does Na+ build up concentration within the PCT?
No, Na+ doesn’t usually build up in PCT but Cl- does so it is drawn in (reabsorbed) with Na+ even through there aren’t any specific transporters.
* There is a significant uptick in Cl- in the later half of PCT
On average, how much protein do the kidneys filter per day?
1.8g of protein filtered each day (in healthy patient)
* 1.7g protein reabsorbed (this is the MAX reabsorption capacity)
so 100mg leftover in urine
How much protein is typically urinated out per day?
Is this enough to cause cloudiness?
100mg of protein is left in urine each day and should NOT make urine cloudy (that is something else or protein wasting and both are bad)
How do filtered proteins return to the body? (Why do we only urinate out 100mg of the 1.8g of filtered proteins?
Proteins are pulled into PC Tubular cells via endocytosis (AKA pinocytosis). They are then broken down/converted into their amino acid forms and stored in the renal interstitium for future use and to increase renal interstitium osmolarity
T/F, Endocytosis/pinocytosis can happen throughout the nephron to help reduce protein wasting.
False, endocytosis/pinocytosis can ONLY happen in PCT
What is the ratio for the sodium/proton (NHE) in the PCT?
NHE rate is 1:1 and is the most prominent path for Na reuptake in the PCT!
Ratio of H+ and HCO3- to make carbonic acid
Proton to bicarb H2CO3 ratio is 1:1
In the PCT, does carbonic anhydrase convert carbonic acid into (HCO3- and H+) or (CO2 and H20)?
In PCT, CA converts H2CO3 into CO2 and H2O so they can diffuse into PC tubular cells.
In the Proximal convoluted tubular cell, does carbonic anhydrase convert carbonic acid into (HCO3- and H+) or (CO2 and H20)?
In the proximal convoluted tubular cell, CA converts H2CO3 into HCO3- and H+ so bicarb can be reabsorbed into the body (via renal interstitium/peritubular capillaries) and protons can be secreted back into the PCT for either excretion from the body or recycling into more carbonic acid.
In Tubular cell, CA drives bicarb and proton conversion from H2CO3
CA Inhibition slows down NA+H+ Exchanger which will lead to less bicarb reabsorption. This will lead to less bicarb in the system and eventually acidosis
Proximal tubular cell break down glutamine into 2(HCO3-) and 2(NH4+). There is an ammonium/sodium ATP pump in the proximal tubular cell to remove the ammonium and excrete it in the urine
Most of our bicarb is produced in the PCT by glutamine conversion
There are a total of 4 molecules made from a single glutamine molecule (X2 bicarb and X2 ammonium)
Phosphate is a good buffer for H+
Calcium gets dragged alongside water into the renal interstitium via paracellular junctions and Ca channels in proximal tubular cells
What type of channel is the calcium transporter in the PCT?
3:1 NCE in PCT cell to get Ca into renal interstitium
CA ATP Pump to get Ca into renal interstitium
parathyroid gland monitors calcium levels and can increase reuptake of Ca in PCT via PTH
PTH can also increase D3 activation
Osteoclasts break down bones and increase in activity from PTH.
* PTH inhibits osteoblast activity
Hypocalcemia leads to osteoporosis
Long-term calcium storage is in the bones
Slide 24 renal cont’d pic Organic cations (Handled by H+ Dependent Antiporter)
Slide 25 renal cont’d pic Organic anions (Handled by Na+ Dependent Antiporter)
* Also, Alpha-Keto Gluterate (aKG) needed for anion transfer.
Picture from Lange Book Figure 5-2
First person to take PCN was 1942
Approximately 2/3 of everything is absorbed in the PCT, especially water
Hippurates use the same transporter as PCN so adding synthetic hippurates=more PCN in circulation (through competitive antagonism)
TAL relatively impermeable to water
NaCl transporter in TAL is the most important.
* It is a primary active transporter (dependent on ATP)
Primary ions reabsorbed in TAL
NA+, K+, Mg++, and Ca++ (Through paracellular diffusion)
Unique feature of TAL in the loop of Henle?
TAL tubular lumen is +8mV (Helps push positive cations back into renal interstitium via paracellular diffusion)
NaCCK pump moves 4 ions (1Na, 2Cl, and 1K) into tubular cell of TAL
Loop diuretics shut down NCCK pump
* Considered most powerful (potent) diuretic class because it dilutes the renal interstitium!
1200mOsm is the maximum concentration of renal interstitium
What is the maximum urine concentration (in mOsm)
1200mOsm because that is as concentrated as our renal interstitium can get
How concentrated can desert lizards make their urine?
Desert lizards can concentrate their urine to 3000 mOsm
1:1 ratio of Na and Cl in DCT transporter (Blocked by thiazides)
Hormones that DCT is sensitive to?
ADH and Aldosterone
* Aldo sensitive cells are called principal cells
*ADH sensitive cells are intercalate cells
Heavy filtration of the glomerular capillaries + Heavy reabsorption at the peritubular capillaries = what?
Bulk Flow
