Physio of PT-Rao Flashcards
The kidney excretes __________, which can be ______ as fast as they are produced in the body.
metabolic waste products which can be toxic as fast as they are produced in the body
Entire plasma is filtered thru the glomerulus how many times each day? That is equivalent to how many times for whole body fluid?
~60 times each day; equivalent to 5 times for whole body fluid
While excreting wastes, how are essential components of glomerular filtrate saved?
by tubular reabsorption
Where does mass reabsorption of glomerular filtrate take place? How much of glomerular filtrate is reabsorbed here? Why is this important?
Proximal tubule; two thirds (85 of 130ml); it is important for regulation of ECFV
What is the primary role of the proximal tubule?
to reabsorb most of the filtered water and solutes
What unique structural feature does the PT have the rest of the tubule does not? What purpose does it serve?
Brush border of the PT; it increases the surface area of the PT, for maximal reabsorptive surface
What type of reabsorption occurs in the PT?
Iso-osmotic reabsorption of glomerular filtrate; 2/3 is reabsorbed which is important for regulation of ECFV
Assuming 1mg/dl (same as plasma) of inulin is filtered and enters the PT, what will the concentration of inulin be as it leaves the PT and enters the Loop of Henle? Why is this so?
3mg/dl; it is not reabsorbed (or secreted), so as 2/3 of filtrate is reabsorbed, its concentration triples. Inulin concentration increases as it gets further from the glomerulus in the PT
What is the equation for Mass flow balance in the PT?
GFR-Reabsorption = Rate of Flow into L of H (V-L)
What is the mass flow equation for inulin in the PT? How do you determine rate of flow into the L of H?
GFR x P[in]=V-L x TF[in];
Rearrange and solve for V-L
Reabsorption in the proximal tubule is what? (in terms of osmolarities)
Iso-osmotic
How many mOsmol/min of solute are filtered? Reabsorbed in PT because it is iso-osmotic? In the flow to the L of H?
130ml/min x 290mOsmol/L=37.7mOsmol/L;
- 6ml/min (or 2/3 of filtrate) x 290mOsmol/L= 25.1mOsmol/min;
- 7-25.1=12.6mOsmol/min flow into L of H
What are the major solutes reabsorbed that contribute to isotonic reabsorption in the PT?
Sodium, Chloride, and Bicarbonate
Where is sodium reabsorbed? How is it reabsorbed?
Along the length of the nephron; via the same active transport mechanism
What accounts for the majority of energy and oxygen consumed by the kidney?
the active transport process of Na+ reabsorption
What seals the space between proximal tubular epithelial cells and separate apical/lumenal membrane from basolateral membrane?
TIght Junctions
What two different Na+ transporters are located on PT epithelial cells? Where are they located?
There are Luminal Na+ Channels and basolateral Na-K-ATPase (NKA) ion pumps
How does the NKA pump work?
It pumps 3 Na+ out into ISF and 2 K+ into the cell, while using up 1 ATP; it is localized exclusively to the basolateral membrane
What is the result of NKA activity?
It creates a driving force for Na+ influx/reabsorption by decreasing intracellular [Na+] and decreasing the membrane potential (more negative). Sodium moves down this large ELECTROCHEMICAL gradient thru apical/lumenal membrane Na+ channels.
Passive diffusion of Na+ down its electrochemical create carries what? What is this used for?
carries high potential energy; this potential energy is used to drive reabsorption of other solutes from the lumen of the proximal tubule
What is the only quantitatively important solute whose transport is directly coupled to metabolic energy in the PT? What is it coupled to?
Na+; secondary active transport
What are the two types of secondary transport seen on the apical/luminal membrane of the PT? Examples of each?
- Cotransport/Symport: Bicarbonate, Nutrients (glucose, amino acids, organic acids)→Na+-Glc Co-transporter
- Antiport/Counter-transport: H+→Na-H+ Exchanger
In order to maintain electro-neutrality, Na+ reabsorption is accompanied by what?
Equivalent amounts of anions
Due to rapid reabsorption of Na+, luminal fluid in the proximal tubule is ____________ than ISF, which drives what?
-5mV more negative; which drives Cl- transport
Leaky epithelium of the proximal tubule favors what kind of anion transport?
Paracellular anion transport
Anion absorption in PCT vs PST?
PST: rapid Cl- absorption
PCT: Cl- absorption reduced, Bicarbonate is absorbed more rapidly (coupled to proton efflux)
How is water reabsorbed?
Massive solute reabsorption decreases osmolarity of tubular luminal fluid and increased ISF osmolarity. This Osmotic Gradient drives water reabsorption facilitated by the leaky epithelium with high hydraulic conductivity (high Kf value)
Water reabsorption accounts for maintenance of what?
It accounts for maintenance of ISO-OSMOTIC reabsorption of filtrate
Side note: What are the different aquaporins found in the tubule and where are they located?
AQP-1: lumenal membrane
AQP-4/5: BL membrane
AQP-2: distal tubule
What are the forces involved in the rapid peritubular capillary uptake of fluid from ISF?
Starling forces across the peritubular capillary endothelium drives rapid uptake of fluid from ISF compartment.
What are the 3 starling forces or Peritubular Factors that drive peritubular capillary uptake of fluid from ISF?
- Positive ISF pressure→ favors uptake
- Low hydrostatic pressure in peritub capillary→ reduced opposition
- High oncotic pressure in peritub capillary→ favors uptake
Reabsorption from PT is _______, but it is also_______.
iso-osmotic, but it is also selective (not all solutes are reabsorbed to the same extent)
How is the concentration ratio of tubular fluid to plasma changed along the length of the PT: (look at diagram)
1.Na+, K+ 2.Cl- 3. Bicarbonate 4.Nutrients (Glc, AA’s) 5.Inulin 6.PAH
- Iso-osmotic
- Slight increase in TF conc due to HCO3- absorption
- High reabsorption
- Almost completely reabsorbed
- No reabsorption (ration increases to 3)
- Ratio higher than inulin due to no reabsorption and active secretion
In the PT, absorption of which is preferred HCO3- or Cl-? What is it driven by?
In PT, HCO3- absorption is preferred over CL-, and it is driven by H+ secretion.
Where are protons secreted in the nephron? Same or different mechanisms?
PT, DT, and CD all actively secrete H+ but differ in the mechanism of proton secretion.
In PT, what mediates proton secretion into the lumen?
Apical membrane Na-H+Exchanger (antiporter) driven by the Na+ gradient
In PT, how is bicarbonate pumped out to the ISF?
HCO3-/Na+ Co-transporter on BL membrane
General Mechanism of HCO3- reabsorption in the PT?
- PT cell: CA converts H2O and CO2 to H2CO3, which dissociates. H+ secreted by exchange; HCO3- reabsorbed by cotransporter.
- In lumen: Secreted H+ and Filtered HCO3- form H2CO3, which CA dissociates into H2O and CO2 which diffuse into cell and start cycle over.
Result: Net Abs of HCO3- but not net secretion of H+. Whenever one bicarbonate is neutralized, one is reabsorbed, not necessarily the same one.
Is this HCO3- reabsorption an active process?
Yes, uses Na gradient to drive H+ secretion and HCO3- reabsorption
How is glucose reabsorbed?
Na+-Glc contransporter (SGLT1 and SGLT2) on the apical membrane are involved, coupled to Na+ gradient
Glucose is completely reabsorbed until it reaches what?
Threshold level
What is the threshold level and what occurs at that level? What about Transport Maximum (Tm)?
a. Threshold (200-220mg/dl)→Reabs Rate<Filtration Rate; Glc first appears in urine, but there is still some increase in Glc reabsorption
b. Tm (370-390 mg/dl)→Na-Glc co-transporters are completely saturated for reabsorption; glucose in urine with no further increase in reabsorption
What is splay?
when glucose concentrations are between threshold and Tm (b/t 250 and 350mg/dl)
What are causes of glucosuria? What does glucosuria cause? Why?
Causes: 1. Pregnancy (lactose and galactose excretion) 2. Diabetes Mellitus 3.Renal Glucosuria: mutation in SGLT1 (int and kidney) and SGLT2 (kidney only)
How are amino acids reabsorbed in the proximal tubule? To what extent are they reabsorbed?
Na-AA Contransporters on the apical membrane reabsorb amino acids, coupled to the Na+ electrochemical potential gradient. AA’s are almost completely reabsorbed (only 0.5-2% excreted)
What are the different types of Na-AA Cotransporters found on the apical membrane?
Neutral, Acidic, and Basic
Reabsorption of organic acids (Krebs cycle intermediates) is coupled to what? To what extent are they reabsorbed?
Na+ electrochemical potential gradient; pretty much completely reabsorbed
Under what condition can organic acid concentration (usually low) exceed reabsorption capacity of the PT?
Diabetic Ketoacidosis
Compare filtration, reabsorption, and excretion of proteins and peptides:
There is low filtration of large proteins. There is greater filtration of peptides, but they are reabsorbed by transporters, so excretion of both is low.
Protein excretion is high in what 3 pathologic states?
Mutiple sclerosis, hemoglobinemia, myoglobinemia
What is phosphate reabsorption coupled to? Why is phosphate partially excreted continuously in urine?
It is couple to Na+ electrochemical potential gradient; because it has a low threshold
At what level is the threshold poised at? What is significant about this?
It is poised at the plasma concentration: change in plasma concentration leads to change in urinary excretion
What regulates the Tm of phosphate? Specific example?
It is regulated by hormones; PTH decreases Tm
Is Chloride actively or passively reabsorbed? Why?
Cl- is passively reabsorbed due 1. concentration gradient created by water reabsorption and 2. electrochemical potential gradient created by Na+ reabsorption.
While 66% of fluid is reabsorbed in PT, what percentage of Cl- is reabsorbed in the PT? Why?
60% of Cl- is reabsorbed in the PT due to active transport of HCO3-.
How is potassium reabsorbed?
Passive transport along the concentration gradient thru the permeant epithelium (thru the junctions)
What is urea? How is it reabsorbed?
Metabolic by-product of protein/AA breakdown. No active transport needed; it is reabsorbed by passive transport but SLOWLY.
How much urea is reabsorbed? What happens if there is an increase in UF?
Only 50% of urea is reabsorbed; increase in UF increase urea clearance
Substances that are freely filtered but not reabsorbed cause what? Some examples of these poorly permeant solutes?
They increase osmolarity and cause diuresis (excessive water excretion); inulin, mannitol
What are clinical significances of poorly permeant solutes that cause diuresis?
Reduction of intracranial and intraocular pressure, promote excretion of toxins, edema.
What are characteristics of mannitol?
Monosaccharide, not produced or metabolized in the body; water soluble and easy to infuse
Why does mannitol cause diuresis?
It is freely filtered and poorly absorbed and there are no transporters for mannitol
What are some examples of things secreted into the PT?
Organic acids and bases, creatinine, PAH, Drugs
How are substances secreted?
Mostly active transport mechanisms; Na co-transporters and other co-transporters
