introduction to the kidney : regulation of Na and glucose Flashcards
what are functions of the kidney?
- maintenance of extracellular fluid volume (ECFV) — Na and H2O
- acid-base balance
- excretion of metabolic waste — urea, creatinine (+ byproducts of drug metabolism)
- endocrine secretion — RAAS, erythropoietin, vitamin D
what are 3 functions of the nephron?
- filtration
- selective reabsorption
- secretion
what happens at the PCT?
reabsorption of water, ions and all organic nutrients
what happens at the loop of Henle?
further reabsorption of water (descending limb) and both Na and Cl (ascneding limb)
what happens in the DCT?
- secretion of ions, acids, drugs, toxins
- variable reabsorption of water, sodium ions, calcium ions (under hormonal control)
what happens at the collecting duct?
variable reabsorption of water and reabsorption or secretion of sodium, potassium, hydrogen, and bicarbonate ions
blood supply order in kidney
renal artery —> segmental artery —> interlobar —> arcuate —> interlobular —> afferent arteriole
what is the name of the capillary network surrounding the nephrons?
vasa recta
what is cardiac output at rest?
average of 5 litres per min
describe renal blood flow
kidneys receive 20% of CO — 1 litre/min
RBF 10-50 x other organs
RBF exceeds O2 requirements of kidneys
RBF not regulated metabolically
blood enters the glomerulus through what?
afferent arteriole
name the highly specialized cells of the kidney glomerulus that wrap around capillaries and that neighbour cells of the Bowman’s capsule
podocytes = part of filtration barrier — stop larger molecules from leaving blood and entering tubular fluid — cut off point is size of albumin
anything small enough being filtered by the glomerulus must enter what before the PCT?
Bowmann’s space
remaining blood leaves the glomerulus via what?
efferent arteriole
what does the glomerulus provide?
size AND charge barrier
- the podocytes and the ECM they produce, and the basement membrane contain a -ve charge to help repel negatively charged ions and molecules
what cells line the DCT?
macula densa
equation for GFR
GFR = Kf x [Pgc - (Pbc + pi gc)]
Kf = filtration coefficient
Pgc = glomerular capillary hydrostatic pressure
Pbc = Bowman’s capsule hydrostatic pressure
pi gc = glomerular capillary oncotic pressure
in the GFR equation, which parts favour filtration and which oppose filtration?
- glomerular capillary hydrostatic pressure FAVOURS filtration (ie. favours the movement of fluid out of blood/plasma into tubule)
- bowman’s capsule hydrostatic pressure and glomerular capillary oncotic pressure OPPOSE filtration
what is oncotic pressure?
osmotic pressure specifically due to proteins
proteins stay in blood — therefore oncotic pressure increases in the capillary as water is lost — attractive force which opposes filtration as it attracts water back into the capillary
why is there no Bowman’s capsule oncotic pressure component in the GFR equation?
it is 0 as there is no filtration of proteins
how much plasma do we filter a day?
180 L/day
what is autoregulation?
maintenance of RBF and GFR despite changes in systemic pressure
- sleep
- exercise
- chronic disease eg. hypertension, renal artery stenosis
what do these graphs show? (auto regulation)
shows that when BP increases, the vascular resistance of the afferent arteriole increases too — this maintains the RBF and GFR
what are 2 mechanisms of autoregulation?
- myogenic — vascular smooth msucle responds to stretch by vasocontricting
- tubuloglomerular feedback — distal tubular flow regulates vasoconstriction
what is the macula densa?
a collection of densely packed epithelial cells at the junction of the thick ascending limb and DCT
the macula densa uses the composition of the tubular fluid as an indicator of what?
GFR
a large vs low NaCl conc indicates what sort of GFR?
large NaCl conc = elevated GFR
low NaCl conc = depressed GFR
describe the mechanism of tubuloglomerular feedback, starting with an increase in arterial pressure
- increase in arterial pressure causes an increased glomerular pressure and plasma flow
- this increases GFR
- this increases flow from PCT to DCT
- there is increased osmolarity of the tubular fluid (ie. increased NaCl)
- macula densa senses this increased flow in the nephron
- the macula densa release adenosine, which acts via A1 receptors on the afferent arteriole to cause constriction
- this increases the preglomerular resistance, thus decreasing the GFR and keeping it maintained at a steady level
when GFR is raised due to an increase in arterial pressure, what limits the increased GFR?
an increase in plasma colloid osmotic pressure
what provides -ve feedback to the increased flow from the PCT to the DCT due to an increased GFR?
an increase in proximal and loop reabsorption = glomerulotubular balance
what is released instead of adenosine by the macula densa if there is a decrease in arterial pressure?
prostaglandin E2 —> activation of RAS —> constriction of efferent arteriole —> increases pressure in glomerulus —> increases GFR
what is renal clearance?
‘volume of plasma which is cleared of substance x per unit time’
way of determining the amount of a substance in a given volume of plasma that is passed through the kidneys and ends up in the urine
renal clearance equation
(urinary conc of x times urine volume per unit time) / plasma conc of x
the ideal marker of GFR should have what qualities?
- freely filtered
- not reabsorbed
- not secreted
- excreted in urine
what is used clinically as a marker of GFR but is affecte by diet, gender, age, ethnicity?
creatinine - byproduct of muscle metabolism, found in blood at relatively constant concs
what is gold standard marker of GFR?
inulin — not endogenous, polysaccharide, has to be infused into blood
what is under research to be the clinical future of GFR markers?
cystatin C
calculate GFR based on the concentrations of a clearance marker in urine of 0.35mol/L, in plasma of 5mmol/L and a urine prodution rate of 2.6 L/day
answer in mL/min
126 mL/min
how much salt is filtered per day and how much is lost in urine?
- 1.5 kg filtered
- 9g lost in urine
why does Na+ need to be regulated?
- plasma [Na+] determines — ECF volume, arterial blood pressure
- less expensive than active water transport (requires less energy to regulate Na+ and have water following passively via osmosis)
- linked to most other renal transport processes eg. glucose reabsorption
what %s of Na+ are reabsorbed in the PCT, LoH, DCT + collecting duct?
- 67% of Na+ reabsorbed in the PCT
- 25% Na+ reabsorbed in the Loop of Henle
- 8% Na+ reabsorbed in the DCT + CD
what are the 2 types of reabsorption?
bulk and fine tuning
as with all epithelial cells, everything in terms of establishing gradients is set up initially by what?
NaK ATPase pump — uses energy to pump K+ into cell against its conc grad, and Na+ out
reabsorption of Na+ in the PCT apical membrane occurs throguh what?
NaH exchanger = NHE-3 (SLC9A3)
in the PCT, Na+ moves in in exchange for H+, taking it out of the cell into the tubular fluid — what do we get coming in to balance toe movement of Na+ in?
get Cl- coming in throguh an chloride anion exchanger (freq uses HCO3-)
how does water form outside the cell in Na+ reabsorption in the PCT?
the H+ (from NHE-3) and anion (HCO3- - from Cl- anion exchanger) come together to form water and CO2
how is H+ recycled in the reabsorption of Na+ in the PCT?
after CO2 forms outside the cell from H+ + HCO3-, the CO2 diffuses back into the cell and combines with water, forming H+ and HCO3- components — recycling
what is aldosterone?
= steroid hormone produced in adrenal cortex. released as a result of stimulation by angiotensin II. it is also stimulated and sensitive to K+ plasma concentration
what does aldosterone cause?
causes epithelial sodium channels (ENaC) to be produced and inserted in the apical membrane, and stimulates these channels to open
also causes the insertion and opening of K+ channels - part of secretory process that allows K+ to be lost and added to filtrate
why is aldosterone secretion in the late distal/collecting duct not a rapid repsone process?
aldosterone binds to its receptor and causes activation of transcription factors, leading to DNA activation and the production and generation of more Na+ channels = not a rapid response process
has a slow (24-48hrs) genomic effect
throguh what does Na+ get reabsorbed in the late distal/collecting duct?
fine tuning under hormonal control
absorbed throguh ENaC (epithelial sodium channels)
what is secreted in the DCT and CD while Na+ is reabsorbed?
K+
what are the 3 transport protein families involved in glucose transport?
- SLC - solute carrier famly
- SGLT on apical
- GLUT on basolateral
SGLT1 vs 2
2 — transports 1 glucose for every 2 Na
1 — transports 1 glucose for every 1 Na
in the early proximal tubule, what are expressed that have a low-affinity but high-capacity for glucose?
SGLT2 and GLUT2
in the early proximal tubule, via what does glucsoe enter then leave the cell?
enters with Na+ via SGLT2 then leaves via GLUT2 (via facilitated diffusion)
in the late proximal tubule, via what does glucsoe enter then leave the cell?
enters with Na+ via SGLT1 and then leaves via GLUT1
what are expressed in the late proximal tubule that have a high-affinity and low-capacity to glucose?
SGLT1 and GLUT1
what is Tm?
under normal circumstances - no glucose in urine as the transproters in the PCT can reabsorb all of the filtered sodium. however they do have a max capacity - Tm = transport maximum
what are normal fasting glucose and GFR values?
- 5mmol/L
- GFR = 125 mL/min
what is the normal transport maximu?
1.25 mmol/min
what happens if you exceed Tm?
lose glucose in urine
describe this graph and what is meant by splay?
this graph shows that once Tm is reached, no more glucsoe can be reabsorbed. excess glucsoe must be excreted
how can you be well below the Tm yet still have glucsoe in urine (seen in chronic kidney disease as a result of t1d)?
overall GFR has fallen because she has lost functioning nephrons
GFR of each single nephron will have actually gone up
now got low global GFR adn there is a build up of uraemic toxins in blood (because not able to get rid of urea because her GFR is low) - toxins damage remaining nephrons and in particular are affecting Na glucsoe uptake — splay actually increases
Tm is reduced as large number of nephorns lost
the kidney itself is a source of glucose via what?
gluconeogenesis — kidney makes around 20% of all glucose in the body, but it then breaks it back down
glucose in the cortex vs medulla
cortex — gluconeogenesis — 300% increase in diabetes
medulla — glycolysis
in a healthy adult, does the amount of salt excreted in the urine over 24 hours match the dietary salt intake over the same period?
yes
what transproter is responsible for the majority of Na reabsorption?
NHE-3
1.4 kg
