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31 Cards in this Set

  • Front
  • Back

Proximal tubule


first part?


second part?


where in the kidney?



PCT 60%


Proximal straight tubule 40%


in the cortex

what feature does PCT have for ↑ absorption

microvilli → brush border

Secondary active transport in PT


types of transporters few examples?

ion chanels


exchangers


cotransporters

Primary active transport in PT


types of transporter example?

pumps



Transcellular movement in PT

through cell

paracellular movement in PT

between cells

Water absorption in PT




how much water is absorbed in PCT?

Na+ movement makes osmotic gradient for water to follow water moves transcellularly + paracellularly passively through AQP1




PT is water permeable implying filtrate is almost isotonic with interstitial space i.e. effectively isotonic with plasma


NB not isosomotic which is a different thing




70% of water is absorbed by the end of the PCT

Na+ movement in PT

down electrochemical gradient into epithelial cells




drives movement of other substances e.g. glucose and AAs and water (by making osmotic gradient)




uses Na+/K+ ATPase to move Na+ out at basolateral

why does water flow paracellularly?

because of net outward hydrostatic pressure in tubule and osmotic forces

Water transport SUMMARY

paracellularly through tight junctions of the epithelial cells




AQP1 transporter apical side, exits AQP1 basal side of epithelial cells

Table of molecules along PT

Table of molecules along PT



think of what substances the body really wants to keep


top 3 conc ↑ because 70% water has been reabsorbed

think of what substances the body really wants to keep




top 3 conc ↑ because 70% water has been reabsorbed

Glucose transport Early PT

Apical


SGLT 2: Na+ + Glucose


Basal


GLUT 2: Glucose





Glucose transport Late PT


want to absorb more Na+ than early PT?

Apical


SGLT 1: 2Na+ + Glucose


Basal passively


GLUT 1: Glucose




harder to absorb Glucose distally as [glucose] ↓

SGLT 2

low affinity high apacity


90%

SGLT 1

high affinity low capacity


10%




distal PT

Max tubular load

2.1 mmol/min

this is tubular maximum transport





Tubular maximum transport glucose

maximum rate of absorption of glucose

Describe the graph 

Describe the graph

If GFR is constant amount filtered proportional to [filtered glucose]




once glucose >≈12mM


reabsorption is limited to 400mg/min


and glucose excretion ↑




difference b/w filtered & reabsorbed → excretion of a substance in this case glucose




Maximum Tubular transport = is max b/w reabsorbed and x axis




e.g. glucosuria in DM

Canagliflozin


Dapagliflozin




class of drugs?


indication?


mechanism? paradoxical


Sx?





SGLT 2 inhibitors

-gliflozin?




Rx for DM




mechanism:


inhibit SLGT 2→ glucosuria → ↓ blood sugar levels



Sx:


↑ risk of UTI


cystitis

AA


Tm?


general trend of transport?


movement by charge?

Max tubular transport Tm is limited




many many different transporters (similar to those from DIG)


Gradient of Na+, H+




Neutral AAs move together


Positiv AAs move together

HCO3-


draw a diagram of the absorption?


which drug interacts with this?


what's special about the _N+/_K+ exchanger? (think NAS)

Acetazolamide

-Na+/H+ exchanger is the most important 
-CO2 diffuses through and reabsorbed back into blood 
-3Na+/2K+ exchanger
-Na+/3HCO3- cotransporter on basolateral side
-HCO3- is driving reabsorption of Na+ normally the other way round i...

Acetazolamide




-Na+/H+ exchanger is the most important


-CO2 diffuses through and reabsorbed back into blood


-3Na+/2K+ exchanger


-Na+/3HCO3- cotransporter on basolateral side


-HCO3- is driving reabsorption of Na+ normally the other way round in nephron


-main mechanism is removal by reacting with excess H+


-CA ↑ rate at which eqm is reached



Acetazolamide


what type of drug is it?


indications?


mechanism?


implications of mechanism

weak diuretic NOT REALLY USED AS DIURETIC




indications:


Glaucoma


mountain sickness -




HCO3- Na+ and water stay in the filtrate




mechanism:stops Carbonic anhydrase from working




implications of mechanism:


so get metabolic acidosis


urine is alkaline


-both of these are becauses HCO3- is not reabsorbed

Acetazolamide and Mountain sickness

ascending to altitude, hypoxia, ↑ respiratory rate, [CO2] ↓, get respiratory alkalosis, since gives metabolic acidosis helps to return to normal pH

how much HCO3- is in the filtrate?

25mM



Cl-


methods of reabsorption?


draw the diagram.

Cl-/Anion exchanger
Paracellular bulk flow?
Cl-/HCOO-
-HCOO- reacts
Cl-/K+
Na+/H+ exchanger

active and passive






main active Cl-/Anion exchanger e.g.


- Cl-/HCOO-


- Cl/HCO3-




to avoid running out of anions to pump into filtrate, HCOO- recycling, helps drive the Cl- uptake




Paracellular bulk flow?




-HCOO- reacts


Cl-/K+


Na+/H+ exchanger

HCOO- in terms of Cl- reabsorption

in filtrate reacts with acidic environment → methoanoic acid

why does [Cl-] ↑ along the length of the PT?



given absorption of HCO3- with charge difference balanced by Na+ absorption


less Cl- is moved than Na+ in early PT


given water is reabsorbed with Na+ and HCO3- this means that [CL-]↑ slightly along PT




distal PT is more permeable to Cl- than HCO3- or other anions


so paracellular reabsorption of Cl- happens

Albumin in PT

little albumin enters filtrate




some does and binds plasma membrane of epithelial cells




→ catabolised to AAs for recycling in the body

Organic anion secretion in PT

Organic anion secretion in PT

PAH 9(p-aminohippuric acid) - organic anion


Furosemide


Penicillin




these compete for excretion




OAT (organic anion transporter) Basolateral membranes




MRP Multidrug resistance associated Protein



MINOR Na+ reabsorption in PT

ENaC epithelial Na+ channels




Na+ channels more prominent in later part of PT allowing 2º active transport





MINOR Na+ reabsorption in PT diagram

Apical side 
ENaC

Basolateral side
 3Na+/2K+
K+ channel

Apical side


ENaC




Basolateral side


3Na+/2K+


K+ channel