Do carnivores have acidic or alkaline urine? How about herbivores?
Carnivores produce acidic urine.
Herbivores produce alkaline urine.
What are the 4 steps of the symplified scheme of excretion?
Filtration, reabsorption, secretion, excretion
Renal secretion plays an important role in ____
potassium handling and acid-base balance
What's the difference between transcellular and paracellular transport? Give examples of each
Transcellular transport is transport through the apical and basolateral membranes. Examples of this include reabsorption (tubular fluid to interstitium to blood) and secretion (blood to interstitium to tubular fluid).
Paracellular transport is transport between the tubular cells. This is regulated by junctional complexes and tight junctions.
The proximal tubule cell has a large brush border. What does this help with?
This greatly increases surface area to help with reabsorption.
Distal tubule cells have less microvilli and mitochondria because less reabsorption happens there.
What are the 3 forms of passive transport?
1. Simple diffusion
2. Facilitated diffusion (carrier-mediated)
3. Diffusion through a membrane channel (pore)
What is simple diffusion?
Simple diffusion is a form of passive transport (does not require ATP) that happens due to electrochemical gradients. The movement is influenced by concentration (move from areas of higher concentration to lower concentration) and charge (difference in charge).
What is facilitated diffusion?
It is a type of passive transportation that is carrier-mediated. Carrier proteins facilitate movement across lipid bilayer. Two or more ions or molecules share the carrier.
What is active transport?
Movement of solute against an electrochemical gradient. Energy is required
True or False: Energy is required to form a urine that differs in solute (S) composition from that of blood/plasma.
For reabsorption, energy is required when [Surine] is less than [Sblood].
For secretion, energy is required when [Surine] is greater than [Sblood].
What is the most important pump/transporter/channel in tubules? Where is it located and what does it do?
The Na+/K+ ATP-ase.
It is located in the basolateral membrane of tubules and it establishes an electrochemical gradient with a net negative intracellular charge and low intracellular sodium concentration. This electrochemical gradient drives most other passive tubular transport processes in the kidney.
It pumps 3 Na+ out per 2 K+ in.
How does the Na/K ATPase drive Na reabsorption?
The Na/K ATPase pumps Na across the basolateral membrane of the tubular cells into the serosa. The decreased Na concentration and net negative charge inside the cell allows Na to diffuse passively from the lumen into the cell where it can be pumped out by the Na/K ATPase.
How does Na reabsorption help in transport of other solutes?
When Na goes from the lumen into the cell (due to the electrochemical gradient formed by the Na/K ATPase), a negative luminal charge is established which drives Cl- between the cells (paracellular transport) to go from the lumen to the serosa.
Also, the reabsorption of glucose and amino acids is helped by Na reabsorption as well. Glucose and amino acids "ride with" Na through secondary active transport.
How does reabsorption of water happen?
Water follows the movement of solutes. So, when solutes are reabsorbed, water follows. This happens through transcellular water pores (aquaporins) and paracellular tight junctions.
Where does most of reabsorption happen?
Proximal convoluted tubule
What primarily happens in the loop of henle?
In the thick, ascending limb of the loop of henle, about 25% of the NaCl is reabsorbed but water cannot follow it because the thick, ascending limb is impermeable to water. This causes a dilution of the urine concentration.
What primarily happens in the distal convoluted tubule?
Fine-tuning of Na balance
What primarily happens in the collecting duct?
Fine-tuning of potassium, sodium, acid-base, and water.
What is special about the thick, ascending limb of the loop of henle?
Impermeable to water
About what percent of water and NaCl is reabsorbed at the different tubular segments?
- proximal tubule
- loop of henle (Ascending and descending)
- distal tubule
- collecting duct
Proximal tubule: 65% NaCl and water
Descending loop of henle: 15% water
Ascending loop of henle: 25% NaCl
Distal tubule: 8-10% NaCl and water
Collecting duct: 6-20% NaCl and water
Note: the collecting duct has the widest range and is based on the physiologic needs of the body.
In the proximal tubule, what % of the following are reabsorbed?
- Amino Acids
- Na = 65%
- Water = 65%
- Glucose = 100%
- Amino Acids = 100%
- Calcium = 60%
- Phosphate = 80%
- Citrate = variable
In the proximal tubule, is H+ secreted or reabsorbed? How about HCO3- ?
In the proximal tubule,
H+ is secreted and HCO3- is reabsorbed.
Are organic anions secreted or reabsorbed in the proximal tubule?
True or False: Macromolecules like polypeptides and proteins are reabsorbed in the proximal tubule.
True. Most of these macromolecules remain in the blood and are not filtered but the ones that are are reabsorbed in the proximal tubule.
What can block the Na-K-2Cl co-transporters in the ascending loop of henle?
Loop diuretics (e.g. furosemide, torsemide, etc)
The thick ascending limb of the loop of henle is impermeable to water. What happens because of this?
This results in a dilution of the urine/filtrate because sodium is being reabsorbed but water cannot follow.
This also results in an increase in medullary osmolarity because sodium is being moved there but not water.
What pump/transporter is responsible for the transcellular Na reabsorption in the thick, ascending loop of henle?
True or False: The reabsorption of Na in the thick ascending limb of the loop of henle is primarily driven by transcellular transport.
False. There is equal transcellular and paracellular reabsorption of Na in the ascending limb of the loop of henle.
The thick ascending limb of the loop of henle has Na reabsorption. What are two other ions that are reabsorbed?
Calcium and magnesium
In the thick ascending limb of the loop of henle, are calcium and magnesium reabsorbed paracellularly or transcellularly?
Which transporter facilitates Na reabsorption in the distal tubules?
What can block this transporter?
Can be blocked by thiazide diuretics.
In addition to Na reabsorption, what are two other ions that are reabsorbed at the distal tubule? What transporter does this?
Calcium and magnesium.
Where in the nephron is the highest activity of Ca-Mg-ATPase?
Distal convoluted tubles have the highest activity of Ca-Mg-ATPase (for reabsorption of Ca and Mg)
What are the major cell types in the collecting tubules? (3)
Intercalated cells (alpha and beta)
What do principal cells in the collecting duct do? (3)
Which segment of the nephron is the "fine-tuning" segment?
What do the intercalated cells of the collecting duct do?
What is ENaC?
ENaC = epithelial sodium channel.
It is the aldosterone mediated channel in the principal cells of the collecting duct that causes Na reabsorption (Na moves from the lumen into the principal cell by itself)
What are ROMK and Maxi-K?
The ROMK and Maxi-K channels are aldosterone mediated channels in the principal cells of the collecting duct that secrete potassium (K)
Aldosterone mediates Na reabsorption and K secretion in the principal cells of the collecting duct. What mediates water reabsorption via aquaporins?
Vasopressin (ADH) mediates the H2O reabsorption via aquaporins in the principal cells of the collecting tubule.
True or False: alpha and beta intercalated cells have opposite functions
What do alpha intercalated cells do? (3)
What about beta intercalated cells? (2)
What's the effect of aldosterone on principal cells of the collecting duct?
In the presence of aldosterone, there are more ENaC channels on the cell apical membrane which increases the reabsorption of Na+ into the principal cells. An increase of Na reabsorption causes a greater negative charge in the lumen which causes an increase in paracellular transport of Cl from the lumen into the serosa.
True or False: In absence of vasopressin, the collecting duct is relatively impermeable to water.
What does vasopressin (ADH) do to principal cells in the collecting duct?
The principal cells in the collecting duct typically only have aquaporins on the basolateral side but not the apical side. When there is vasopressin (ADH) present, aquaporins are formed on the apical side so that water can pass from the lumen through the cell into the interstitium.
Without vasopressin, the collecting duct is impermeable to water.
What is countercurrent multiplication?
Energy is spent in the thick, ascending limb of the loop of henle to reabsorb ions into the medulla. This increases the osmolarity of the medulla which can multiply the amount of water that can be passively reabsorbed in the descending loop of henle.
What is the vasa recta?
Vasa recta are loop shaped capillaries that maintain the osmotic gradient in the medulla with passive movement of water and solute.
In the descending capillaries, water moves out of the blood into the interstitium and solute moves from the interstitium into the blood. (This is because the medulla is hypertonic so water travels from the blood capillary to the interstitium to try to dilute the concentration and solute moves from the interstitium into the blood capillary because it's moving from higher concentration to lower concentration.
In the ascending capillaries, water moves from the interstitium into the capillaries and solute moves from the capillaries out into the interstitium
The _____ _____ establishes the osmotic gradient from the cortex to the medulla of the kidney and the _____ _____maintains the osmotic gradient.
countercurrent multiplication, vasa recta
Is water reabsorption in the collecting duct passive or active?
Passive. The countercurrent multiplication system establishes a high ion concentration in the medulla. This means that water wants to leave the collecting duct to go into the medulla and this happens as long as there are aquaporin channels open (when vasopressin/ADH is present).
Is peritubular capillary oncotic pressure high or low?
It is very high. The glomerulus doesn't filter most proteins, it just filters waters and solutes. So, the blood in the capillaries is concentrated with proteins and cells which gives it a high oncotic pressure.
Solutes and water are reabsorbed from the lumen (urinary space) back into the medulla. How does the water and solutes make it from the medulla back into circulation?
This is driven by starling forces. The high peritubular capillary oncotic pressure attracts water and solutes back into circulation.
Explain glomerulo-tubular balance (GFR and volume of ultrafiltrate)
When there is an increase in GFR, there is an increase in the volume of ultrafiltrate. About 65% of the volume, regardless of the increase, is reabsorbed at the proximal convoluted tubule. The remainder of the excess volume is dealt with downstream by an increase in oncotic pressure in the peritubular capillaries. (When GFR increases, blood in the efferent arteriole and peritubular capillaries is more concentrated because more water is being filtered out by the glomerulus. This increase in peritubular capillary oncotic pressure results in more water being taken from the medulla back into the capillaries).
However, these mechanisms aren't enough to fully compensate. The rest of the balance is done by tubulo-glomerular feedback.
What is tubulo-glomerular feedback?
TGF is the mechanism that occurs when excess delivery of NaCl is sensed by the macula densa at the end of the thick ascending limb. The macula densa sends a signal to afferent arterioles to constrict. This lowers GFR which lowers ultrafiltrate volume.
How does flow rate influence tubular function?
As solutes and water flow through tubules, they pass different reabsorptive mechanisms. If the flow is faster, there is less time for interaction with the transporters so less solute and water are absorbed. If the flow is slower, there is more time for interaction with transporters so more solute and water are absorbed.