What are the five major stages of urine formation?
Glomerulus: filtration of blood
Proximal tubule: reabsorption of filtrate; secretion into tubule
Loop of Henle: concentration of urine
Distal tubule: modification of urine
Collecting duct: final modification
What are the 3 major functions of the nephron?
Filtration: of blood to produce a filtrate
Reabsorption: of water, ions and organic nutrients from filtrate
Secretion: of waste products into tubular fluid
What are the characteristics of Filtration as a basic renal process?
in glomerulus
force for filtration:
blood pressure
different diameter of afferent and efferent arterioles
Glomerular Filration Rate (GFR): rate at which glomerular filtrate is produced
Can be measured clinically and used as an indicator of renal function
How does glomerular filtration work?
Filtrate passes through:
Pores in glomerular capillary endothelium
Basement membrane of Bowman's capsule
Epithelial cells of Bowman's capsule (podocytes) via filtration slits into capsular space
What are the forces acting on glomerular filtration?
Push fluid out of glomerulus:
PGC: glomerular capillary hydrostatic pressure
πBS: Bowman's space oncotic pressure (almost 0)
Oppose ultrafiltration:
PBS: Bowman's space hydrostatic pressure
πGC: Glomerular capillary oncotic pressure
By the end of the glomerular capillary, Net filtration pressure reduced to almost 0.
GFR generally remains constant even when systemic BP changes.
Why does GFR generally remain constant even when systemic BP changes?
autoregulation of renal blood flow
What is Autoregulation of Renal Blood Flow (RBF)?
local effect (not neuronal/hormonal)
Two hypotheses:
Myogenic: due to response of renal arterioles stretch (Starling's law)
Metabolic: renal metabolites modulate arteriolar contraction, eg adenosine, NO
What does GFR depend on?
diameters of afferent and efferent arterioles
Eg:
Afferent artery dilates, efferent artery constricts: increased GFR
eg via Prostaglandins, ANP, dopamine, NO, kinins
Afferent artery constricts, efferent artery dilates: decreased GFR
eg via Noradrenaline, endothelin, adenosine
How can changes in GFR alter systemic blood pressure?
drop in filtration pressure → drop in GFR → less Na enters proximal tubule → mascula densa senses the change → stimulate juxtaglomerular cells → release RENIN → angiotensin II (vasoconstrictor) → increased BP → increased filtration pressure → normal GFR
What happens in the proximal tubule?
reabsorption
What is the driving force for reabsorption in proximal tubule?
Na / K ATPase
What does the brush border allow?
more surface area for reabsorption
How is the Na concentration of peritubular cells?
low
due to Na/K ATPase pumping Na out
How is the charge of PT cells overall?
negative
due to presence of intracellular proteins
How does reabsorption occur in the PT?
Na/K ATPase → Na pumped into capillary → low Na conc in cell → Na diffuses into PT cell from lumen → Cl follows Na → water follows through aquaporin channels (AQP)
How does the transcellular flow of water occur?
through aquaporins (AQPS) in cell membrane
What are the 4 major renal AQPs?
AQP-1 : proximal tubule
AQP-2 : collecting duct, expression controlled by ADH
AQP-3&4 : basolateral surface of tubular cells
How does glucose reabsorption from PT occur?
co-transported with Na
What does glucose reabsorption in PT occur through?
two systems:
S1 (PCT):
into PCT cells: SGLT2
out of PCT cells (into blood): GLUT2
S3 (proximal straight tubule PST):
into PST cells: SGLT1
out of PST cells into blood: GLUT1
Glucose is co-transported into PT cell with Na very efficiently so very little is excreted.
How can glucose be present in urine in diabetics?
glucose transporters become saturated
so some glucose can't be reabsorbed and escapes into urine
What does Tm mean in the glucose titration curve?
maximum transport capacity of glucose (transport maxima)
urinary excretion of glucose indicates diabetes
How do SGLT2 inhibitors work in diabetes and what are some examples?
inhibit SGLT2 transporters so glucose isn't reabsorbed into blood