Tubular Absorption and Secretion Flashcards
What parts of excretion is tightly controlled? What has no control?
Filtration has no regulation.
Absorption and secretion are tightly regulated
Which molecules have 100 or nearlt 100% filtered load reabsorbed?
Glucose
Bicarb
Sodium
Chloride
What molecule has 50% filtered load reabsorbed?
Urea
What molecule has 0% filtered load reabsorbed?
Creatinine
Where does the majority of reabsorption happen?
- Majority reabsorption in proximal tubule (60%)
- Little in loop of henle and distal tubule
- In general, of the total filtrate coming into the nephrons, the proximal tubule reabsorbs:
- ▪ 65% to 70% of the Na + and H 2 O
▪ 80% to 85% of the K +
▪ 65% of the Cl −
▪ 75% to 80% of the phosphate
▪ 100% of the glucose
▪ 100% of the amino acids
After this bulk reabsorption, “fine-tuning” of the reabsorption of the remaining tubular fluid occurs in subsequent segments of the nephron.
What are the 2 different pathways that the nephron absorbs substances?
Transcellular- most common way.
Paracellular- pulling from between cells. Junctions in nephron very tight, so not a lot of paracellular movement
What is active transport?
Using ATP to move molecules against their concentration gradient
What is secondary active transport
- Secondary active transport is how we absorb everything in kidney
- Everything uses secondary active transport except reabsorbing bicarb
- Uses energy of created concentration gradient to move other ion (sometimes the ion being brought in is going against concentration gradient)
- i.e. Na/K ATPase creates gradient. Decreases Na inside cell
- Now sodium can come into cell, bringing glucose, which glucose can be coming in against its concentration gradient
Where is countertransport used in kidney?
To secrete substances into nephron
What is exception to rule for absorption in kidney?
Bring in bicarb with counter transport (typically we secrete with counter transport)
What is the general location for transporters in cellular membrane of kidney?
- High [Na] and [Glucose] in tubule,
-
Apical membrane
- Bunch of Na/Glucose symporter channels
- Create [Na] gradient by Na/K ATPase pump on basolateral membrane
- Allows us to move Na and glucose down created concentration gradient, into cell
- GLUT-2 transporter on basolateral membrane to facilitate with diffusion into capillary
What is Tmax?
Transport max.
- Maximum amount of solute transport can handle. Property of the channel
- After Tmax, will begin to see solute excreted in urine
What is splay?
- reference to heterogeneity of nephron, some shorter, some do not have a lot of tubule. That’s why there’s a curved line at filter and excretion
- Why we see glucose in urine before we expect it
Which substrates are absorbed in proximal tubule?
- Glucose
- Amino acids
- Acetate
- Krebs cycle intermediates
- Water-soluble vitamins
- Lactate
- Acetoacetate
- Many others
- all are 100% reabsorbed attached to Na
What are some characteristics of typical transport process?
- They are (secondary) active
- They manifest a Tmax
- Well above what is normally filtered
- They manifest specificity
- They are inhibitable by drugs and disease
What is filtered load?
GFRx Px
- Filtered load= how much moves to blood into nephron
- Na has highest filtered load of any ion
- Under hormonal control
- For excretion, we can go as low as 5% or as high as 99% based on bodies needs
- Na is reabsorbed in 3 areas:
- 1) Proximal tubule (65-75%)
- 2) Part of loop of henle (15-20%)
- 3) Distal tubule and top of collecting duct (5-7%)
What is ion movement in Na/K ATP ase pump?
2 K in for 3 Na out using ATP
What is the only antiport in proximal tubule?
Na/H antiport for acid/base regulation
What does movement of Cl in proximal tubule look like?
- As Na absorbed, H2O follow
- Moving lots of positives into intracellular space
- Cl- then comes in because of positive gradient created
- Cl- is pulled in via paracellular pathway
- Only allowed because strong electrochemical gradient created
Describe this graph.
- [Na] stays the same because taking H2O with it (line remains at 1)
- As going down tubule, reabsorbing mass Na and water follows
- Lost Na down tubule, but [Na] does not change!
- So much Na is reabsorbed!!
- Amino acids, HCO3, glucose curve down because concentration is so much lower than Na.
- These are absorbed at beginning of tubule
- Inulin’s line, not reabsorbed or excreted!
- Cl- line is delayed increase because it follows electrochemical gradient created by Na
Describe the loop of henle, purpose and what is absorbed there.
- Shaped like horseshoe, essential to function of creating osmotic gradient
-
Descending limb- completely impermeable to solute, no reabsorption/secretion
- ONLY permeable to H2O
- AKA Concentrating segment
-
Ascending limb- impermeable to H2O permeable to solute
- Aka-Diluting limb
What types of transporters are found in thick ascending loop of henle?
- Basolateral membrane= Na/K ATPase pump
- Inside lumen, sodium will move down concentration gradient
- 4 things moving in via transporter on apical membrane=
- 1 Na
- 1 K
- 2 Cl
- Other transporters to allow K/Cl to be reabsorbed/ Not focusing on that right now
What are the 2 types of cells in distal tubule?
Principal Cell
Intercalated cells
What is transported on principal cells?
- Na/K ATPase on basolateral membrane
- Na out, K in, low concentration Na gradient in cell
- Na/Cl symporter on apical side
- Cl molecule has chloride channel on basolateral membrane, Cl able to move out on own via channel
What is role of alodsteron on distal tubule?
- Aldosterone is lipophilic, can cross cell membrane easily, goes to nucleus and increases protein
- Makes 3 protein:
- Make Na-K ATPase to go on basolateral membrane
- Make Na-channel on apical membrane
- Also opens K channel on apical membraneà secretion
- This causes use to absorb more Na, therefore more H2O and therefore increasing blood volume.
- Aldosterone secretes K and absorbs Na/H2o
How do diuretics work?
- Diuretics- make you urinate
- Block reabsorption of Na in tubule (so h2o doesn’t get reabsorbed)
- Either turn off Na/Cl symptomer on apical membrane, or turn off aldosterone mediated Na channel on apical membrane
What is the osmolarity in proximal tubule?
Isoosmotic (absorbing Na, other solutes, and H2O)
Losing mass, not concentration!
What is osmolarity like in descending loop of henle?
Hyperosmotic
absorbing only H2O, impermeable to solutes
What is osmlarity like in ascending loop of henle?
Hypoosmotic
Impermeable to h2o, reabsorbing solutes
What is osmolarity like in distal tubule?
Hypoosmotic
Reabsorbing H2O and solute
Remains same concentration as from ascending loop of henle
What is osmolarity in collecting duct?
Hypoosmotic
- concentration is going to be dilute; hyposmotic as low as 100mOsm/L. This is where it decides how concentrated we want it with ADH
Potassium handling by kidney?
- Potassium is interesting ion because potassium is low in ECF, but a lot of K in bodies
- K is high in ICF
- we have more ICF volume in general, so we have more K than Na, but K not as relevant because it’s staying inside the cell
- K is regulated by hormones and things that happen inside cell (unlike Na which is regulated by kidney)
- Lots of tissue stores of potassium, but every time you use insulin/epi/aldo, will move K in/out
- K is not 100% regulated by kidney like Na
- K absorbed in GI tract in the colon
- Excrete 5-10 mEq K/day via feces
- Excrete 90-95 mEq/K in urine
How do we usually handle K on a typical diet (normal-High K diet)
We have net secretion of K
In a low K diet, how do we alter K transport?
In low K diet, we change distal tubule configuration so it reabsorbs K
How do we reabsorb K in proximal tubule of nephron
Bulk Flow
- don’t need to know specifics, just know that as Na/H2O/Solutes are brought in membrane, K gets caught up in paracellular pathway and brought into cell
What is absorption of K like in thick ascending limb?
Comes in via Na/2Cl/K symporter transporter on apical membrane
How does aldosterone affect K?
- How K secreted in distal tubule comes down to aldosterone
- Aldosterone:
- Open Na channel
- Create more Na/k ATP ase on basolateral
- Open K channel on apical membrane- secrete K
- As we pump more Na into cell, K is going to be secreted into lumen
- Increases basolateral Na/K ATPase activity, pumping more K into the cells. K is then secreted into lumen through apical aldosterone sensitive channels.
How does K affect aldosterone?
- Aldosterone also mediated by K level
- If increase K level, causes increase aldosterone secretion
- This causes an increase in K secretion
- Increase in plasma excretion
What does decrease in calcium levels stimulate?
- A decrease in calcium causes: release of PTH
- To kidney to increase Ca reabsorption
- Bone- breakdown Ca stores
- Increase amount Vitamin D from kidney causes increase absorption of Ca in intestine
What does increase in Ca levels trigger?
- Reduces Ca uptake in kidney
- Stimulate Ca deposition in bone
What 3 areas play role in Ca levels?
Gi tract
Kidney
Bone
Where is Ca reabsorbed? What is interesting about its interaction with phosphate?
- Reabsorbed at same places as Na
- Proximal tubule
- Loop henle
- Distal tubule
- Ca with phosphate- when bound, NOT active
- If you want to increase Ca, need to decrease phosphate at same time in order to increase bioactive Ca (and vice versa)
Where are most PTH receptors located?
Distal nephron has most dense area of receptors
How is Ca absorbed in proximal tubule?
TALH?
- For Ca reabsorption in proximal tubule, we don’t know HOW it happens, but it DOES happen
- We do know how it’s absorbed in loop henle and distal tubule
- In Loop of Henle:
- When PTH is bound:
- On apical membrane- opens up Ca channelCa is normally VERY low inside cell
- Ca floods inside cell
- On basolateral: Ca-ATPase pumps all Ca all out, reabsorbing Ca into blood
- Both Ca channel and ATPase are regulated by PTH. PTH increases both
- Don’t worry about Ca paracellular transport
Distal Tubuel absorption of Ca?
- Distal limb has same mechanism as TALH. Ca channel on apical, basolateral has Ca/ATP ase
- Also has Ca/Na antiport transporter on basolateral
Aldosterone’s site of action? Effect?
Site of action: Distal tubule/CD
Effect: increase NaCl, water reabsorption, increase K secretion
ADH site of action? Effect?
Site of action:
- Proximal tuuble- effect= increase NaCl, water reabsorption. Increase H secretion
- Distal tubule/CD- effect= increase water reabsorption
What is ANP’s site of action, effect?
Site of action: distal tubule/CD
Effect: decrease NaCl reabsorption
What is PTH’s site of action, effect?
Site of action: PT, TALH, DT
Effect: decrease phosphate reabsorption, increase Ca reabsorption
