Kidney Function I: Filtration, Reabsorption, and Secretion

• key equations:

  
  

  equation linking flow, pressure difference, vessel length, radius of vessel lumen, and blood viscosity?

  flow = ( pressure difference x πr^4)/ 8Lη

  
  

  L= vessel length

  r= radius of vessel lumen

  η= blood viscosity
• key equations:

  
  

  equation explaining Resistance to flow (Poiseuille's Law)?

  Resistance = 8Lη/πr^4

  
  

  L= vessel length

  r= radius of vessel lumen

  η= blood viscosity
• key equations:

  
  

  equation linking flow, pressure difference and resistance?

  Flow = Pressure difference / Resistance
• what are the 3 pathways a substance can take in the nephron?

  1) it is filtered and secreted but no reabsorbed

  e.g. para-aminohippuric acid (PAH)

  
  

  2) it is filtered and is reabsorbed, but some escapes in the urine

  e.g. water and most electrolytes

  
  

  3) it is filtered and completely reabsorbed.

  e.g. glucose
• What is the amount excreted in urine equal to?

  Amount filtered + amount secreted - amount reabsorbed
• what is metabolism in the kidney?

  the renal tubule cells can remove substances from the blood/glomerular filtrate and metabolise them

  -> resulting in their disappearance from the body

  
  

  e.g. glutamine
• tubular secretion: ORGNAIC BASES (cations)

  
  

  how are organic bases secreted in the proximal tubule?

  1. Organic cations (OC) enter proximal tubule cell via facilitated diffusion transporters.

  2. OC enter tubule lumen via counter-transporters
• tubular secretion: ORGNAIC BASES (cations)

  
  

  Give examples of endogenous (within body system) and exogenous (outside body system) molecules


  endogenous:

  - creatinine

  
  

  exogenous:

  - drugs, e.g. morphine
• tubular secretion: ORGNAIC ACIDS (anions)

  
  

  how are organic anions secreted in the proximal tubule?

  1. Organic anion (OA-) enters epithelial cell via organic anion counter transporters..

  2. OA- enters tubule lumen via ATP- dependent primary active transporters
• tubular secretion: ORGNAIC ACIDS (anions)

  
  

  Give examples of endogenous (within body system) and exogenous (outside body system) molecules


  endogenous:

  - bile salts

  
  

  exogenous:

  - drugs, e.g. penicillin

  - diagnostic agents, e.g. para-aminohippuric acid (PAH)
• tubular secretion

  
  

  
  

  Tubular secretion is the only means of excretion for some protein bound molecules. True or False?

  TRUE
• tubular secretion

  
  

  How many steps are there in tubular secretion?

  It's a 2-step membrane transport process that includes distinct transport systems at the brush border and basolateral membranes of epithelial cells. These transporters are broadly selective for organic anions or cations
• What is tubular secretion?

  The movement of solutes from the peritubular capillaries into the tubules

  - occurs in proximal tubules and collecting ducts
• tubular reabsorption

  
  

  How are the vast majority of filtered proteins reabsorbed in the PCT?

  By endocytosis, where they are then degraded to amino acids inside the cell, which is important for the inactivation of small polypeptide hormones e.g. insulin & growth hormone
• tubular reabsorption

  
  

  How many amino acid transporters are expressed in the PCT?

  At least 8, 6 of which are Na+ dependent
• tubular reabsorption

  
  

  what happens when reabsorption is above 200mg/dl?


  the threshold is reached.

  so, the sodium-dependent glucose cotransporters are saturated with glucose and the transfer maximum is reached.

  
  

  -> as a result, glucose will appear in the urine
• tubular reabsorption

  
  

  What is filtered load linearly proportional to?

  Plasma concentration, and it matches reabsorption below 200mg/dl
• tubular reabsorption

  
  

  where does the basolateral membrane of tubule cells face?

  The peritubular capillary
• tubular reabsorption

  
  

  where does the luminal membrane of tubule cells face?

  The filtrate
• tubular reabsorption

  
  

  give a summary of how glucose is reabsorbed

  Filtered glucose normally reabsorbed

  
  

  - SGLT-Na+-dependent glucose co-transporter = remove glucose from lumen

  - GLUT facilitated transporter = into interstitium

  - Na+-K+-ATPase pump = maintains low Na+ conc in cell
• tubular reabsorption

  
  

  
  

  How is glucose reabsorbed in the PCT?

  - glucose is pumped against its conc. gradient from the tubular lumen into the tubule epithelial cell across the luminal membrane via Na+/glucose symporter (SGLT-2)

  There is a coupling the movement of glucose to the movement of sodium (which is moving down its conc. gradient)

  -> the sodium conc. gradient (lower conc inside cell) is due to the sodium potassium ATPase pump on the basolateral membrane (energy to do this is provided by the hydrolysis of ATP to ADP by enzyme ATPase)

  
  

  
  

  -glucose is exited across the basolateral membrane of the tubule cell by GLUT.

  (it moves down the conc. gradient inside the cell (interstitial fluid) and then it enters the blood of the peritubular capillaries by diffusion)
• tubular reabsorption

  
  

  What is the filtrate-plasma ratio of glucose?

  1
• tubular reabsorption

  
  

  what is the molecular weight of glucose?

  180 DA
• tubular reabsorption

  
  

  what is reabsorbed into the PCT by passive reabsorption?

  urea

  chloride

  potassium

  calcium
• tubular reabsorption

  
  

  What does the proximal tubule reabsorption of many solutes depend on?

  The presence of a sodium-linked transporter in the luminal membrane which is saturable & has a limited capacity (tubular maximum)
• tubular reabsorption

  
  

  what do Na+-coupled transporters transport?

  glucose

  amino acids

  phosphate
• tubular reabsorption

  
  

  what 3 things help the proximal reabsorption of organic nutrients


  - Na+-coupled co-transporter

  - tubular maximum system

  - specific transporters
• tubular reabsorption

  
  

  what are the walls of the proximal tubule like?


  the walls are a single layer of columnar cells.

  
  

  -> the tubule contains:

  -microvilli which increases the SA for reabsorption on the luminal membrane

  - mitochondria to generate ATP to provide energy for the many transport proteins involved in reabsorption
• what is tubular reabsorption ?

  The movement of materials from the filtrate in the tubules and into the peritubular capillaries

  - can occur throughout the nephron

  (is greatest in the proximal tubule)
• GFR

  
  

  how does surface area affect GFR?

  intraglomerular mesangial cells surround glomerular capillaries and increase in sympathetic activity which causes the cells to contract and reduce surface area for filtration.

  This decreases GFR.
• GFR

  
  

  how do Permeability characteristics affect GFR?

  the glomerular capillaries have a much larger pore diameter than the majority of other capillaries; this makes them highly permeable and leads to a high filtration rate ( high GFR)

  
  

  glomerular capillaries pore: 15nm

  majority of other capillaries pore: 5-12nm
• GFR

  
  

  how does dilation of afferent arteriole increase GFR?


  it increases the radius and increases blood flow.

  - this increases hydrostatic pressure and so increases GFR
• GFR

  
  

  how does constriction of afferent arteriole decrease GFR?

  it reduces the radius and reduces blood flow.

  - this decreases hydrostatic pressure and so decreases GFR
• GFR

  
  

  how does pressure control net glomerular filtration pressure?

  Plasma will flow across a capillary wall:

  - From a high to a low hydrostatic pressure,

  - From a low to a high colloid osmotic pressure.

  
  

  net glomerular filtration pressure causes the fluid to move by bulk flow from the capillary lumen to the bowman space.
• GFR

  
  

  how does GFR depend on filtration pressure?

  - Hydrostatic pressure difference (pressure of fluid against the wall):

  aids filtration

  
  

  - Colloid osmotic pressure difference (pressure exerted by large molecules which are unable to cross the membranes):

  opposes filtration
• GFR

  
  

  what does GFR depend on?

  1) Net filtration pressure (result of opposing starlings forces)

  2) Permeability characteristics

  3) Surface area
• GFR

  
  

  what does a higher GFR mean?

  greater excretion of salt and water
• GFR

  
  

  what is GFR regulated by?

  both neural and hormonal input to the afferent and efferent arterioles
• GFR

  
  

  since urine output is typically 1.5l/day due to reabsorption (and GFR is 180l/day), what percentage of water is filtered and reabsorbed?

  99%
• GFR

  
  

  what is the average GFR in a 70kg person?

  125 ml/min of filtrate formed (180 l/day)