Renal physiology Flashcards
filtrate definition
liquid that has passed through a filter
urine in this case
lumen definition
inside space of a tubular structure
urinary space= tubular space
paracellular definition
between the cells
absorption between cells of the tubule
basolateral definition
surface below/to the side
surface of the tubular cell next to the bloodstream
osmolality definition
concentration of a solution
diffusion definition
movement of molecules from high to low concentration
reabsorption definition
movement of substance from tubular lumen into the blood
secretion definition
movement of substance from blood into tubular lumen
concentration of the filtrate
osmolality and movement of molecules along concentration gradient
also movement of molecules by active transport facilitated by transporters
structure of the kidneys
retroperitoneal
T12-L3
blood supply= renal arteries directly from aorta
25% of circulating blood
right lower than the left of to the weight of the liver
cross section of the kidney
functional unit/ nephron
functions of the kidney
filtering
reabsorption
secretion
what is each nephron comprised of
afferent arteriole
glomerulus
efferent arteriole
macula densa
PCT loop
DCT
collecting duct
2 types of nephron
cortical
juxtaglomerular
cortical nephron
glomerulus that sits high in the cortex
loop that enters medullar superficially
juxtaglomerular nephron
low lying glomerulus in cortex
loops that extend deep into the medulla
label the image
purple is glomerulus
gold is arteiroles
tight proximity of glomeruli
3 main functions of the kidney
homeostatic function
hormonal influence
protein catabolism and gluconeogenesis
homeostatic function
blood pressure
urine production, filtering reabsorption of sodium and water
osmolality, salt and water balance
hormonal influence
rennin
angiotensin 2
PG-E
endothelia
bradykinin
EPO
calcitriol
how much filter does the kidney receive daily and then how much urine is produced
180L
but reabsorb 99% filtrate so urine 1-2L per day
summary of actions in the connecting segment and cortical collecting duct
aldosterone mediated potassium secretion by principal cells
hydrogen ion secretion by alpha intercalated cells
potassium reabsorption by alpha intercalated cells
ADH-mediated water reabsorption
summary of actions in the medullary collecting duct
potassium reabsorption or secretion
final NaCl reabsorption
ADH-mediated water ad urea reabsorption
hydrogen ion and Nh3 secretion
summary of actions in the distal tubule
small amount of NaCl reabsorbed
active regulation of calcium excretion
summary of actions in the loop of henle
countercurrent multiplier
reabsorption of 15-25% of filtered NaCl
active regulation of magnesium excretion
summary of actions in the proximal tubule
isosmotic reabsorption of 65-70% filtered water and NaCl
reabsorption of 90% of filtered HCO3
major site of NH3 production
reabsorption of almost all filtered glucose and amino acids
reabsorption of potassium, phosphate, calcium, magnesium, urea and irate
=summary of actions in the glomerulus
filtratio
cells in each part of nephron
specialised tubular cells
designed to optimise function at each stage
afferent and efferent arterioles basic
control flow of blood through glomerulus
afferent= arriving
efferent= exiting
afferent and efferent arterioles functions
able to constrict and relax
repsinsbile for controlling and influencing interglomerular flow, pressure and filtration
what are afferent and efferent arterioles controlled by
starling forces
blood pressure too low, arterioles
constrict efferent arteriole to increase flow and pressure
RAAS
blood pressure too high, arterioles
constriction of afferent to reduce hydraulic pressure in the glomerulus
intrinsic mechanisms for renal auto regulation
Renal autoregulation - the kidney itself can adjust the dilation or constriction of the afferent arterioles, which counteracts changes in blood pressure. Thisintrinsicmechanism works over a large range of blood pressure, but can malfunction if you have kidney disease includes arteriole myogenic mechanism and tubular glomerular feedback (more later)
extrinsic mechanism nervous control
nervous system and hormonal control can override renal auto regulation ad decrease the glomerular filtration rate when necessary
large drop in BP: nervous system stimulate contraction of afferent arteriole sympathetic vasoconstriction due to epinephrine and constriction of afferent reducing urine production
can also activate RAAS
extrinsic mechanism hormonal control
atrial natriuretic peptide is a hormone that can increase glomerular filtration rate
hormone produced heart
secreted when plasma volume increases
increasing urine production
decreased resistance in afferent
increased RBF increased GFr
use CCB or alpha 1 blockade
increased resistance in afferent
decreased RBF and GFR
use NSAIDs via PG inhibition
decreased resistance in efferent
increased RBF and decreased GFR
use ACEi or ARB
increased resistance in efferent
decreased RBF and increased GFR
RAAS activation
RAAS system
effects of AT2
constrict efferent arteriole to maintain glomerular blood flow
stimulation of ADH secretion from pituitary to reabsorb more water in collecting ducts
stimulates aldosterone secretion from adrenals
acts on DCT to reabsorb more water and sodium
net effect is increase in BP
macula densa
area of closely packed specialised cells lining the wall of the distal tubule
cells sense sodium chloride concentration in distal convoluted tubule
tubuloglomerular feedback
decreased sodium to the macula densa
decreased sodium to macula densa tubuloglomerular feedback
relaxes afferent arteriole
increases renin from juxtaglomerular cells
increases renin from juxtaglomerular cells tubuloglomerular feedback
relaxes afferent arteriole tubuloglomerular feedback
Increases glomerular hydrostatic pressure
Helps increase GFR
relaxes afferent arteriole tubuloglomerular feedback
Increases glomerular hydrostatic pressure
Helps increase GFR
increases renin from juxtaglomerular cells tubuloglomerular feedbakc
Activation of RAAS
Vasoconstriction of efferent arteriole
Increased intraglomerular hydrostatic pressure
Sodium and water reabsorption downstream
3 layers to filter from blood to Bowmans space
Endothelium
Basement membrane
Podocytes (epithelium)
endothelium in filter
negatively charged layer with fenestrations
basement membrane in the filter
produced by endothelium and podocytes
negatively charged collagenous and non collagenous matrix with channels
podocytes in the filter
“interdigitating foot processes” that prevent large molecules from entering urinary space; phagocytic function engulf macromoleclues trapped in slits.
mesangium in the filter
not a layer; but filler tissue which anchors the whole structure from the arterioles to the peritubular capillaries.
Bowmans capsule
collects urine
glomerular filtration
water freely filtered
small charged particles freely filtered (Na+, K+, Cl-, glucose, urea)
large particles not filtered, red blood cells
minimal filtration of smallish negatively charged particles e.g. albumin. this barrier repels negatively charged proteins
why is the control of intraglomerular pressure crucial
too much
too little
causes problems
too much hintraglomerular pressure
breakdown of the filter
leaking of larger molecules into Bowman’s space inc. blood and protein
Haematuria and proteinuria
too little intraglomerular pressure
Not enough flow
Fall in filtration and GFR
drugs we use in glomerulus
ACE inhibitors and Angiotensin 2 Receptor Blockers
ACE is the enzyme to convert AT1 to AT2
AT2 causes efferent vasoconstriction to increase pressure and filtration in the glomerulus
ACEi no AT2 no effect on efferent arterioles, and also no knock-on BP
Reduction in intraglomerular pressure -> reduction in GFR
Long term protective effect and preservation of renal function
measuring GFR
Creatinine isproduct of creatine muscle metabolism
Almost constant rate of production
Freely filtered
Minimally reabsorbed and secreted
Allows estimation of GFR when adjusted for muscle mass, age and sex
CKD EPI – eGFR
proximal convoluted tubule, how to think pf it
as heavy lifter of the nephron
receives 180L per day of filtrate that is iso-omotic with plasma
no RBC’s
virtually no protein
iso-osmotic
approx same number of small molecules and ions
proximal convoluted tubule
Bulk of the reabsorption (60%) of the filtrate
90-100% reabsorption of glucose and aminoacids
Transporters (sodium – glucose, sodium – phosphate, sodium –amino acid)
Paracellular reabsorption
Reabsorption AND secretion, e.g. Sodium – hydrogen antiporter
Na/H antiporter aids in bicarbonate reabsorption
glucose handling in the kidney
early proximal tubule
late proximal tubule
early proximal tubule
High capacity-low affinity Na-Glu symporter – SGLT2
Reabsorbs most of filter glucose
Diffusion out of cell across basolateral membrane via GLUT2 transporter
late proximal tubule
Low capacity-high affinity Na-Glu symporter - SGLT21
Reabsorbs remaining glucose
Diffusion out of cell across basolateral membrane via GLUT1 transporter
glycosuria and diabetes
Glucose is freely filtered at glomerulus and reabsorbed in PCT
High plasma glucose levels (10-12 mmol/L) saturates SGLT transporters
Overspill of glucose into urine
Osmotically active particle
Diuresis (increased urine production)
water reabsorption in the PCT
Interstitium now hyperosmotic
Osmotic movement of water across tight junctions and aquaporins
Hydrostatic pressure in interstitium increases
High oncotic pressure within peritubular capillaries (proteins)
Push and drag of water into capillaries
Fluid in PCT is now iso-osmotic with plasma again
polyuria
excessive urination
polydypsia
excessive thirst
loop of henle how to think of it
engine of the nephron
descending into the medulla
hairpin turn back out and into the cortex
loop of henle function
Starts at end of PCT and finishes at the macula densa.
Remaining 40-45% of filtrate not handled by PCT
Reabsorptionof 25-35% of Na⁺ and Cl⁻
First time we’re seeing salt and water reabsorption separated
Water is passive in the descending limb, sodium is active in the ascending limb
loop of henle NKCC
The main channel in the Loop used to reabsorb Na⁺, K⁺ and Cl⁻
1. Na⁺, K⁺, 2Cl⁻ enter
2. K⁺ spat back out
3. Paracellular transport
recycling ROMK channel
that spits potassium back into the tubule creating a negative change within the cell and a positive charge inside the tubule allowing the paracellular reabsorption of positively charged sodium, calcium and magnesium
counter current mechanism in the loop of henle
steep concentration ngradient
maximise Na+ reabsorption
filtrate leaving the loop of henle is hypo-osmotic with plasma
drugs used in loop of henle
Loop diuretics (as the name suggests)
Furosemide
Bumetanide
Act on the NKCC to inhibit reabsorption of Na⁺, K⁺ and Cl⁻
Increases the osmolality of the filtrate
Reduced concentration gradient less water reabsorbed by diffusion
diuresis and natriuresis.
what to think of the distal convoluted tubule as
nephron site of intelligent and qualitative sodium and water reabsorption for what is beneficial to the body
distal convoluted tubule function
Starts from the macula densa and ends at connecting segment
“Fine tuning” of remaining 5% of Na⁺ and Cl⁻
Sodium-chloride co-transporter (NCCT)
Na⁺/H⁺ exchanger and Cl⁻/HCO₃⁻ exchanger
NO water reabsorption here
transport mechanisms in the distal convoluted tubule
NCCT – does exactly what it says on the tin
- Also powered by Na⁺K⁺ATPase
- Blocked by thiazide diuretics e.g. bendroflumethiazide, indapamide
Na⁺/H⁺ exchanger = Na⁺ in, H⁺ out
Cl⁻/HCO₃⁻ exchanger = Cl⁻ in, HCO₃⁻ out
H⁺ + HCO₃⁻ = H₂CO₃ ⇌ H₂O + CO₂
10-15% of calcium reabsorption occurs here under influence of PTH and vitamin D (mostly in Loop)
distal convoluted tubule Na+
Low intracellular Na+
NCCT takes up sodium
Impermeable to water
Filtrate leaving the DCT becomes more dilute -50 mosm/L
brief function of collecting ducts
fine tuning reabsorption and secretion
2 main segments of collecting dust
cortical
medullary
collecting ducts
Potassium excretion and sodium reabsorption (ENaC and Na,K,ATPase) – principle cells
Acid-base handling – intercalated cells
Hormonal influence – aldosterone and ADH
Urea reabsorption via UT-A1 and UT-A3 (urea recycling)
water reabsorption in CD
Tubular side is impermeable to water
BUT Permeabilitycan be increased
Insertion of aquaporins (water channels) into tubular membrane
Under ADH influence
Basolateral surface is permeable
Water moves into the interstitium via osmosis
This osmotic gradient has been set up by the LoH countercurrent multiplier
ENaC function
reabsorb sodium and water inresponse to aldosterone-> potassium secretion
drugs used in collecting ducts
Mineralocorticoid antagonists (MRAs) e.g. spironolactone reduce sodium and water reabsorption in the distal nephron drop in BP
MRAs cause hyperkalaemia
overexpresison of ENaC
Liddle’s syndrome (Autosomal dominant cause of hypertension associated with hypokalaemia)
diabetes insipidus
Non-response of ADH to V2 receptors = Nephrogenic diabetes insipidus
Reduced production of ADH = Cranial diabetes insipidus
