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Substance Concentration
K+ 20-70 mEq/L
Pi 20-40 mEq/L
Urea 200-400 mM
Creatinine 6-20 mM
pH 5.0-7.0
Osmolality 500-800 mOsm/kg H2O
Glucose 0
Amino acids 0
Protein 0
Blood 0
Ketones 0
Leukocytes 0
Bilirubin 0
Tubular Reabsorption
Involves both active and passive
mechanisms
Transcellular route
Paracellular route
Ultrafiltration (bulk flow)
Tubular Reabsorption
Active Transport
Against an electrochemical gradient
Requires ATP
2 types:
1. Primary
2. Secondary
Tubular Reabsorption
Osmosis
Water diffusion from a region of low solute
concentration to a region of high solute
concentration
Primary Active Transport
Can move solutes against an
electrochemical gradient
Energy comes from the hydrolysis of ATP
Includes the following:
1. Na-K ATPase
2. Hydrogen ATPase
3. H-K ATPase
4. Ca ATPase
Primary Active Transport
Na-K ATPase
Transports Na ions into the interstitium
Maintains: 1) low intracellular Na and 2)
high intracellular K
End result: -70mV inside the cell
Primary Active Transport
Na- K ATPase
Involves 3 steps:
1. Na diffuses across the apical membrane
into the cell membrane
2. Na is transported by the Na-K ATPase
pump
3. Na, water and other substances are
reabsorbed to the peritubular capillaries
by ultrafiltration
Na- K pump pix
Secondary Active Transport
2 or more substances interact with a
carrier molecule and are transported
together across the membrane
Does not require energy directly from ATP
and from high energy phosphate sources
Can either be co-transport and counter-
transport
Glucose and amino acid co-
transport
Na-H countertransport
Secondary Active Transport
Pinocytosis
Reabsorbs large molecules eg. Proteins
Requires energy
Secondary Active Transport
Transport maximum
Limit to transport of solute (reabsorption
and/or secretion)
Saturation of specific transport systems
Tubular load exceeds the capacity of the
carrier proteins
Can be increased by hormones, eg.
aldosterone
Secondary Active Transport
Glucose Transport System
Found in the proximal tubule
All filtered glucose is reabsorbed
Transport maximum: 375mg/min – all
nephrons have reached their maximal
capacity to reabsorb glucose
Filtered load of glucose: 125mg/min
Secondary Active Transport
Threshold for glucose
Appearance of glucose in the urine
Occurs before the transport maximum is
reached
Reason: not all nephrons have the same
transport maximum for glucose
Transport Maximum of Substances
Actively Reabsorbed
Substance Transport Maximum
Glucose 375mg/min
Phosphate 0.10 mM/min
Sulfate 0.06 mM/min
Amino acids 1.50 mM/min
Urate 15 mg/min
Lactate 75 mg/min
Plasma protein 30 mg/min
Transport Maximum of Substances
Actively Secreted
Creatinine 16 mg/min
PAH 80mg/min
Actively Transported but No
Transport Maximums
Substances that are passively
reabsorbed do NOT demonstrate a
transport maximum
Gradient-Time Transport
Also seen in some actively transported
substances, eg. Na reabsorption
Determined by:
1. Electrochemical gradient for diffusion
2. Permeability of the membrane for the
substance
Water Reabsorption
Occurs through osmosis
Osmotic flow of water occurs through the
tight junctions
Seen in the proximal tubule – high
permeability for water and most ions
Water Reabsorption
Solvent Drag
Solutes carried when water moves across
the tight junctions by osmosis
Changes in Na reabsorption influence
reabsorption of water and solutes
Water Reabsorption
Proximal Tubule – high
Loop of Henle – low
Last part of the tubules – high or low
Passive Diffusion of Cl, urea and
other solutes
Cl ion diffusion
Caused by electric potentials brought
about by Na
Na goes out leaving the inside negatively
charged compared to the interstitial fluid
Diffuses through the paracellular pathway
Can be reabsorbed by secondary active
transport, eg. Na-Cl co-transport
Na+ reabsorption
H2O reabsorption
Lumen
Luminal Cl- Luminal urea
negative
concentration concentration
potential
2. Intercalated Cells
Reabsorb K ions
Secrete hydrogen ions into the lumen
Late Distal Tubule and Cortical
Collecting tubule
Principal Cells
Depends on the activity of the Na-K
ATPase pump
Na reabsorption and K secretion
Primary sites of K sparing diuretics
1. Aldosterone antagonists: spironolactone,
eplerenone
2. Na channel blockers: amiloride,
triamterene
Late Distal Tubule and Cortical
Collecting tubule
Intercalated Cells
Mediated by a hydrogen ATPase
mechanism
Secrete hydrogen ions and reabsorbs K
Plays a key role in acid base regulation of
body fluids
Late Distal Tubule and Cortical
Collecting tubule
Functional characteristics:
1. Completely impermeable to urea
2. Reabsorb Na ions – controlled by
aldosterone
3. Intercalated cells – acid-base regulation
4. ADH/ vasopressin – controls permeability
to water
Medullary Collecting Duct
Absorbs <10% of filtered Na and water
Final site of processing of urine
Important role in final urine output of water
and solutes
Epithelial cells are cuboidal in shape
Relatively few mitochondria
Medullary Collecting Duct
Special characteristics:
1. Permeability is controlled by ADH
2. Permeable to urea
3. Secretes hydrogen ions – role in acid-
base balance
Medullary Collecting Duct
> 1.0 : more water is reabsorbed than
solute; net secretion of the solute into the
tubular fluid
< 1.0 : more solute has been reabsorbed
than water
1.0 : concentration of the substance in the
tubular fluid is the same as the
concentration in plasma
Measurement of Water
Reabsorption
Inulin
Used to measure GFR
Not secreted or reaborbed
Changes in inulin reflect changes in the
amount of water in the tubular fluid
10 minute break
Regulation of Tubular
Reabsorption
Glomerulotubular Balance
Most basic mechanism for controlling
tubular reabsorption
Intrinsic ability of the tubules to increase
their rate of reabsorption in response
increased tubular load
Occurs independent of hormones
Glomerulotubular Balance
Total rate of reabsorption increases as the
filtered load increases
Helps prevent the overloading of the distal
tubular segments when GFR increases
Second line of defense: buffers
spontaneous changes in GFR on urine
output (first line: autoregulatory
mechanisms~ tubuloglomerular feedback)
review autoregulation
Peritubular Capillary and Renal
Interstitial Fluid Physical Forces
Dopamine
Paracellular
Loop of Henle 25% 1 Na+-1K+-2Cl- Aldosterone
symport
Distal tubule ~4% NaCl symport Aldosterone