A. TUBULAR FUNCTION Flashcards
what is unique about each tubular segment of the nephron
they each express different channels/transporters and hence have different properties
what barriers does the filtrate have to cross to be reabsorbed into plasma of peritubular capillaries (tubule to blood)
- apical/luminal membrane
- cytosol of tubular cell
- basolateral membrane
- interstitial fluid
- capillary wall of peritubular capillaries
what tubular cells polarised or non-polarised
polarised
what are different ways molecules can move out of the filtrate
- transcellular (through the cell) by diffusion or actively
- paracellular diffusion (through tight junctions)
what molecules can pass through the membrane by passive diffusion
- lipophilic molecules eg - steroid hormones
- gases
what is diffusion
- passive as no energy involved
- down concentration gradient or electrochemical gradient
how does water diffuse across membranes
osmosis: net movement or diffusion of solvent molecules through a selectively-permeable membrane from a region of high water potential to a region of low water potential
what molecules pass by simple diffusion
- gases
- lipophilic molecules
what molecules pass by facilitated diffusion through channels and carriers
hydrophilic molecules
what is active transport
- against a concentration or electrochemical gradient
- primary: coupled directly to an energy source (eg hydrolysis of ATP)
- secondary: coupled indirectly to an energy source
what is the transport maximum, Tm
- capacity of carrier exceeded ie - fully saturated
- so remaining of solute is stays in filtrate and isn’t transported
- eg: glucose transporter is saturated in diabetes causing glycosuria and osmotic diuresis
role of PCT
primary site of reabsorption for all solutes, dependent on the action of Na+/K+ ATPase
what is reabsorbed from the PCT into the blood
- Na+, Cl-, K+, HCO3
- glucose
- water
- urea
- amino acids
what is secreted from blood into PCT
organic acids/bases
mainly an active process:
- organic anion (OA-) transport (e.g. bile salts, urate/ uric acid)
- organic cation (OA+) transport (e.g. adrenaline, NA, dopamine)
- drugs include diuretics (OA-), penicillins (OA-), opioids (OA+)
what antiporter is on the basolateral membrane in the PCT
- Na+-K+ ATPase pump (carrier)
- 3 Na+ out of the tubular cell
- 2 K+ from interstitial fluid into the tubular cell
- hydrolyses ATP to ADP (primary active transport)
- low to high concentration (against conc grad)
- tubular cell becomes more negative
what antiporter is on the apical membrane in the PCT
- Na+/H+ antiporter
- secretion of H+ (from water) from tubular cell to tubule lumen
- against conc grad
- secondary active transport
what symporter is in the basolateral membrane in the PCT
- HCO3-/Na+
- net effect is reabsorption of HCO3-
what symporter is in the apical membrane in the PCT
- Na+/glucose symporter (SGLT-2)
- also Na+/ amino acid symporter
(secondary active transport)
what transporter is in the basolateral membrane in the PCT
- GLUT-2 transporter
- facilitated diffusion
- down conc grad (high to low)
what channel is in the basolateral membrane in the PCT
- K+ channel
passive reabsorption of water in PCT
- by osmosis
- through ‘leaky’ tight junctions and via water channels, aquaporins (trans cellular)
- high water permeability
- also facilitated by osmotic gradient caused by Na+ reabsorption
passive reabsorption of Ca2+, Cl- and K+ (some Na+) in PCT
- by paracellular transport, as a result of active reabsorption of Na+ at basolateral membrane
passive reabsorption of urea in PCT
- 50% of urea is reabsorbed
- indirectly linked to Na+ reabsorption
- reabsorption of water secondary to Na+ reabsorption creates a concentration gradient that favours passive reabsorption of urea due to conc urea in filtrate
- reabsorbed down conc grad from high to low
role of loop of henle
- NaCl and water reabsorption
- creation of hyperosmotic renal medullary interstitium
which provides osmotic gradient for water reabsorption - controls concentration of urine
what forms the juxtaglomerular apparatus
macula densa cells (tubular) and juxtaglomerular granular cells (vascular)
where is the juxtaglomerular apparatus located
where the DCT passes the fork formed by afferent and efferent arterioles
what is the role of the macula densa cells
(tubular cells)
- detect conc of NaCl in tubular fluid
- involved in the tubuloglomerular feedback mechanism
what is the role of juxtaglomerular granular cells
(modified SM cells)
- secrete renin
- present in the vascular component
- most numerous in theafferent arteriole
- involved in the tubuloglomerular feedback mechanism
how can the kidneys auto regulate rapidly
- they change blood pressure by adjustment of the diameter of the afferent arteriole by:
1. myogenic properties of arterioles: intrinsic, ie will resist stretch of vascular walls if BP too high
2. tubuloglomerular feedback
tubuloglomerular feedback with increased arterial pressure
- increased GFR due to increased glomerular hydrostatic pressure and hence increased net pressure
- increases flow rate in loop of Henle so less time for Na+ and Cl- reabsorption in LoH
- conc of NaCl at macula densa cells is increased
- sensed by macula densa cells at top of ascending limb of LoH
- macula densa cells secrete vasoconstrictive agents:
endothelin
adenosine (more likely)
ATP (more likely) - through paracrine signalling: into IF, transferred in IF to granular cells and SM cells of afferent and efferent arterioles
- causes an increase in resistance to blood flow (decreased) in afferent arterioles (vasoconstriction) returning GFR towards normal
myogenic activity with increased blood pressure
- stretching of blood vessels is resisted by SM cells by narrowing of afferent arteriole (VC)
- decreased blood flow
- decreased hydrostatic pressure
- decreased GFR
TGF activity with increased blood pressure
- adenosine/ATP reaches SM cells of afferent arteriole causing VC etc
tubuloglomerular feedback with decreased arterial pressure
- decreased GFR due to decreased glomerular hydrostatic pressure and hence decreased net pressure
- decreases flow rate in loop of Henle so more time for Na+ and Cl- reabsorption in LoH
- conc of NaCl at macula densa cells is decreased
- sensed by macula densa cells at top of ascending limb of LoH
- macula densa cells secrete vasodilatatory agents:
PGs: PGE1, E2, I2
Bradykinin
NO (most likely) - through paracrine signalling: into IF, transferred in IF to granular cells and SM cells of afferent and efferent arterioles
- causes a decrease in resistance to blood flow (increased) in afferent arterioles (vasodilatation) returning GFR towards normal
myogenic activity with decreased blood pressure
- less stretched so there is relaxation of afferent arteriole to maintain good blood flow
TGF activity with decreased blood pressure
- NO causes vasodilation?
angiotensin II causing vasoconstriction with decreased blood pressure
- macula densa cells communicate to juxtaglomerular cells
- increased renin release from granular cells of afferent and efferent arterioles
- renin stimulates angiotensin II production causing vasoconstriction of efferent arterioles, thus returning GFR towards normal
role of the early DCT
- reabsorbs Na+, K+, Cl-, Ca+ but is virtually impermeable to water and urea
what antiporter is on the basolateral membrane in the early DCT
- Na+-K+ ATPase pump (carrier)
- 3 Na+ out of the tubular cell
- 2 K+ from interstitial fluid into the tubular cell
- hydrolyses ATP to ADP (primary active transport)
- low to high concentration (against conc grad)
- tubular cell becomes more negative
- creates grad for reabsorption of Na+ down its conc grad with Cl-
what symporter is in the apical membrane in the early DCT
- Na+-Cl- symporter
- Na+ and Cl- enter tubular cell
what channels are present in basolateral membrane of early DCT
- Cl- channel
- K- channel
- both enter interstitial fluid
what is the late DCT and CD composed of
- principal (P) and intercalated (I) cells
- P-cells reabsorb Na+, Cl-, water and secrete K+
- I cells reabsorb K+ and HCO3- and secrete H+
what antiporter is present in basolateral membrane of P-cells
- Na+-K+ ATPase pump (carrier)
what channels are present in basolateral membrane of P-cells
- Cl- channel
- K+ channel
- both enter interstitial fluid
what channels are present in apical membrane of I-cells
- Na+ selective channels (ENaC)
- enters tubular cell by passive diffusion as Na+ low (reabsorbed)
- K+ channel
- enters tubular lumen (secreted)
what hormones take action in P-cells
- aldosterone (increase Na+ and water reabsorption and K+ secretion)
- ADH (increase permeability to water so increased reabsorption)
what transporter is in the basolateral membrane of I cells
- HCO3- carrier (transporter)
- K+ channel
- both enter interstitial fluid
what pump is in apical membrane of I-cells
H+-ATPase
- H+ pumped out against its own grad
what antiporter is in apical membrane of I-cells
- K+/H+-ATPase
- K+ into tubular cell and H+ into tubular lumen
what effect does aldosterone have in I cells
stimulates H+ secretion
% of Na+ reabsorbed in different segments of nephron
65% from PCT
25% from LoH
5% from DCT
5% from CT
<1% excreted in urine
% of K+ reabsorbed in different segments of nephron (low intake)
65% from PCT
20% from LoH
5% from DCT
10% from CT
<1% excreted in urine
% of K+ reabsorbed in different segments of nephron (high intake)
65% from PCT
20% from LoH
10-50% kept in DCT
5-30% kept in CD
15-80% excreted in urine
% of glucose reabsorbed in different segments of nephron
98% from PCT
2% beyond PCT
0% excreted as we want to keep glucose to use as energy
% of glucose reabsorbed in different segments of nephron (plasma glucose conc ≥10mmol/L)
Tm for glucose reabsorption is exceeded, glucose appears in urine
ie - Na+/glucose co-transporters saturated in PCT
