Flashcards in L20– Glomerular Filtration and Tubular Transport Deck (79):
How is water content controlled by urine?
By urine volume (if water in deficit > concentrated urine > smaller loss of water)
What three things are controlled by urine composition?
Electrolyte balance (Na+, K+, Ca2+, Cl-, PO43-
Acid/base balance (pH of body fluids)
Excretion of nitrogenous/metabolic waste
How is blood pressure related to urine production?
Indirectly, by blood volume which is related to urine volume
What is the distribution of nephrons in the kidney's medulla vs cortex?
90% = cortical
10% = juxtamedullary
Each nephron has which 2 capillary beds?
Glomerulus + Peritubular capillary and Vasa Recta (formed from efferent arterioles exiting glomerulus)
In the two types of nephrons, are both renal corpuscles in the cortex?
Yes, one in cortex, other in juxtamedullary cortex
Which type of nephron has a longer Loop of Henle?
Which two tubules lie adjacent to the glomerulus?
PCT and DCT
What are the three basic functions of a nephron?
In which vessels do tubular secretion and tubular reabsorption take place?
Peritubular capillaries and Vasa Recta
What 2 cells are important in the glomerulus capillaries?
What are the modified cells on the visceral layer of the Bowman's capsule?
What is the role of the Mesangial cells in glomerulus?
Specialized smooth muscle cells
Do not collapse, structural role
Contract/ relax to control blood flow to glomerulus (contract = reduce filtration rate)
3 components of renal corpuscle filtration barrier?
Fenestrated endothelium of glomerular capillaries
Fused basal lamina of endothelial cells and podocytes
Filtration slits of podocytes
What forms filtration slits? What is size of slit?
Podocytes' feet interdigitate
Slits only 20-30nm wide
What is ultrafiltration dependent on? (think properties of what goes through)
Molecules ultra-filtrated under HIGH PRESSURE based on SIZE and CHARGE
Glomerular capillaries have fenestrations that does what?
Allow macro-molecules to pass
Prevent cells to pass
What component of the renal corpuscle filtration barrier sort molecules by charge?
2. membrane (GBM): made of collagen
negatively charged = repels negatively charged proteins)
What is the role of glomerular basement membrane?
Prevents filtration of large plasma proteins (radius = 7-10nm)
Slows passage of smaller plasma protein
What is the final glomerular filtration barrier?
Glomerular epithelial cells + slit diaphragm
What are some substances that can pass through the glomerular filtration barrier?
ions e.g. Na+, Cl-, H+, K+
Does filtration barrier have much effect on small charged particles
Are molecules larger than 8nm filtered?
Why is albumin not filtered?
Due to negative charge repelled by GBM and size
What is a sign of chronic kidney disease associated with protein in urine? How does it occur? (think what chronic diseases and how the micro-structure is changed)
Proteinuria/ albuminuria or urine albumin >300mg/24 hours
Result from diabetes, hypertension, kidney inflammation...
Fusion or collapse of podocyte foot process, splitting of GBM, altered exoskeleton of podocyte
How much protein/ time is considered severe nephrotic syndrome?
Pressure favouring filtration?
hydrostatic capillary pressure = 55
Pressures opposing filtration?
Glomerular capillary oncotic pressure (due to suspension in plasma e.g. albumin)
Bowman's capsule hydrostatic pressure ( = 15
What does rate of ultrafiltration depend on?
Balance of forces favouring and opposing filtration
How is high pressure generated in ultrafiltration?
Blood pressure from Afferent arteriole
Efferent arteriole narrower than Afferent arteriole
How is net filtration pressure calculated?
glomerular capillary blood
hydrostatic pressure (GBHP) - Bowman’s capsule hydrostatic pressure (CHP) - Glomerular/blood capillary oncotic pressure (BCOP)
How does the composition of glomerular filtrate compare to plasma?
Composition of water, electrolytes, wastes is almost identical to plasma
Exception: proteins, RBCs are kept out from filtrate
How much glomerular ultrafiltrate is made each day and how much is reabsorbed?
kidney makes ~180 L of glomerular ultrafiltrate per day
~179 L is retained
What is the normal Glomerular Filtration Rate? GFR
Total volume of filtrate formed by BOTH kidneys per minutes
GFR (90-140 mL/min)
How can net filtration pressure (NFP) increase?
Increase by: Vasodilation of AFFERENT arteriole and Vasoconstriction of EFFERENT arteriole
What is the effect of vasodilating afferent arteriole?
Increase blood flow to glomerular > increase capillary blood pressure > Increase net filtration pressure
What is effect of vasocontricting Efferent arteriole?
Increase capillary pressire
How can NFP be decreased?
Vasoconstrict Afferent arteriole or
Vasodilate Efferent arteriole
What is the effect of Vasoconstricting afferent arteriole?
Decrease blood flow to glomerulus
Decrease glomerular capillary blood pressure
What is the effect of Vasodilating Efferent arteriole?
Decrease glomerular capillary blood pressure
What 3 things does GFR depend on?
Net filtration pressure
Permeability of filtration membrane
Surface area available for filtration
What are the stages of GFR?
Stage 1 >90mL/min Structural kidney damage with normal function
Stage 2 60-89mL/min
Kidney damage with mild loss of function
Stage 3 30-59mL/min Mild > Moderate> Severe Kidney damage
Stage 4 15-29mL/min Severe kidney damage
Stage 5 <15mL/min Kidney Failure
How can GFR be determined by a substance?
Renal clearance of a substance NEITHER reabsorbed NOR secreted by kidneys can be used to determine GFR
How is clearance calculated?
Excretion amount of substance (mass per minute)/ Concentration of substance in body (conc.)
What substance is used for good estimating GFR?
Inulin (and sinistrin)
Freely filtered, Not reabsorbed nor secreted
So diuretic drug would have no effect on inulin clearance
Why is creatinine used as a rough measure for eGFR?
Inulin administration is time consuming
Creatinine is slightly secreted so eGFR is slightly higher than actual
How does excretion relate to filtration, reabsorption and secretion?
Filtration - reabsorption + secretion = excretion
What affects GFR?
age, gender, food intake, muscle mass...etc
What is the formula for GFR?
GFR= (urine concentration (of inulin) x urine flow)/ Plasma concentration (of inulin)
What are the two routes for reabsorption pathways in Renal tubule?
Transcellular route and Paracellular route
In which tubule does most reabsorption happen?
70% reabsorption in PCT
Sequence of movement in transcellular route? (think what to cross)
Transport across Apical membrane of tubule cell > Diffuse through cytoplasm > Transport across basolateral membrane > Move through interstitial fluid > Move through capillary endothelium
Sequence of movement through paracellular route?
Directly bypass cell via leaky tight junctions through lateral intercellular space
Transport through apical membrane > move out of cell to lateral intercellular spaces
What is the epithelium of all tubules in kidney except collecting duct (*not collecting tubule)?
Collecting duct has simple columnar
What transport mechansim for paracelullar route movement?
What substances use paracellular?
Diffusion down concentration gradient
e.g. urea, Ca2+, K+...
What transport mechanisms for transcellular route?What substances use transcellular?
Primary active transport, secondary a.t. , facillitated diffusion, osmosis
e.g. glucose, water, glucose... etc
Give examples of symport, antiport on the apical membrane of tubules.
Symport = same direction of transport as Na+
e.g. Glucose and Na+
Antiport: opposite direction to Na+ movement
e.g. Na+/ H+ pump
What causes Na+ deficiency inside tubule cell and allows apical membrane secondary active transport?
Na+/K+ pump on basolateral membrane generates Na+ concentration gradient inside tubule cell
How does glucose move through tubule cell?
Symport at apical membrane
Facillitated diffusion at basolateral membrane
What is the name of channels involved in glucose movement in tubule cells?
Na+/glucose cotransporter/ symport channel = SGLT2
Facil. diffusion channel/ Uniporter at basolateral membrane = GLUT2
What is the anitport channel on apical membrane of tubule cells ?
Na+/H+ exchanger = NHE3
What is the primary active transport carrier name on basolateral membrane in tubule cells?
What is the name of Cl-/Base exchanger on apical membrane in tubule cells?
How does DCT absorb NaCl?
absorbs NaCl mainly via an Na+-Cl- cotransporter
In which tubule is paracellular route observed?
Is the fluid leaving PCT iso-osmotic to plasma?
What follows Na+ movement generated by Na+/K+ ATPase on basolateral membrane?
What is tubular transport maximum (Tm)?
For substances reabsorbed via transporters (mainly secondary active transport), the number of available carriers determines Tm
Relationship between concentration gradient and reabsorption rate for active transport substances?
Completely reabsorbed until all available carriers become
saturated > reach tubular maximum > no further increase in resorption even if concentration gradient increases more
What substances are abosorbed by secondary active transport?
Ca2+, Cl-, H+, organic solutes, phosphate
How does Glycosuria occur?
Amount of glucose in filtrate exceed maximum number of transporters/Transport maximum of PCT
How does filtration rate and conc. grad. relate?
Filtration normally increases in proportion to plasma
concentration (freely filtered)
Talk through processes of movement for Na+
Apical: Facillitated Diffusion/ involved in cotransport
Basolateral: Active transport with K+
Process of mvt. for Water
Osmosis on apical and basolateral
Process of mvt. for Ca2+
Diffusion on apical
Osmosis on basolateral
(Transport of Na+ creates an osmotic gradient > H2O follows (transcellular / paracellular) > leads to
concentration gradient for Ca2+ > resorption of Ca2+ (transcellular)
Process of mvt. for Cl-?
Apical: Diffusion (mostly paracellular)
Basolateral: Electrochemical gradient (with H20 and Na+)
Process of mvt. for K+
Apical: Paracellular diffusion
Basolateral: Facillitated Diffusion
Glucose, amino acid, HPO4_ reabsorption?
Apical: Facillitated co-transport with Na+
Basolateral: Diffusion (Na+/K+ pump)