Urinary System
L 2, 3 Tubular Reabsorption & secretion
Prof. Madaya Dr Than Kyaw
1, 8 October 2012
Tubular Reabsorption & secretion
Reabsorption
• For reabsorption a substance
- must pass from tubular lumen through tubular epithelial cells
- diffuse through interstitial fluid (ISF)
- enter the capillary
Secretion
• For secretion a substance
- must leave the capillary
- diffuse through ISF
- pass thru tubular epithelial cells into the lumen
Reabsorption and secretion
Reabsorption of Na+, Cl-, glucose and A/A
• Substances important for body functions (e.g. glucose, a/a)
enter tubular fluid by filtration at the glomerulus
• Due to their relatively small molecular size - pass easily thru’
glomerular membrane
• Concentration in the filtrate and plasma the same
• If they are not returned (not reabsorbed) to blood – they are
excreted in the urine and lost from the body
Proximal convoluted tubules
Proximal convoluted tubules
- the longest part; make up most of the renal cortex
- cuboidal cells with a luminal border modified with microvilli (brush border)
providing large surface area
- important substances like glucose and amino acids - 100% reabsorption
Glucose or
A/A in
Tubular lumen
Diffuse into
peritubular capillary
Transport coupled
with transport of Na
Carrier protein
No additional
energy needed
for glucose or A/A
Na+ + glucose
or
Na+ +A/A
Active transport
(energy used Na+ -K + -APTase)
Reabsorption and secretion
• Once inside the tubular cell – A/A or glucose uncoupled from
the carrier
• Diffuse basal or lateral border to ISF → capillaries
• Na+ – actively transported from tubular epithelial cells to ISF
and then to capillaries
• The carrier protein return to its previous conformation to
transport more glucose /amino acids/ Na+
• Unlike other tissues, glucose in the renal tubules and
instestine is actively and continually transported even though
its concentration in the lumen is minute; thereby loss of
glucose from the body is prevented by active transport (uphill)
• Active transport needs both carrier and energy
Reabsorption and secretion
Transport of Na+ from tubular
lumen into the tubular
epithelial cell and
its co-transport with glucose.
Energy requirement is provided
by the Na+ -K + -APTase (sodium
pump)
Protein channel (carrier protein):
Protein channel:
- pores; contain a single or a cluster of proteins;
- specificity for certain substances or restrictive due to the size.
- Water easily diffuses through protein channel.
- Transported molecule enters the carrier protein channel and
bind with the receptor. After binding the carrier protein
undertakes conformational change to open the channel on
the opposite side.
- Then transported molecule is released and carrier protein
returns to original conformation for transport of another
molecules.
Reabsorption and secretion
Some low molecular weight substances
- bound to plasma proteins
- retained in the blood plasma
E.g. - calcium, iron, hormones (e.g. thyroxine)
- only a small fraction of them that are unbound pass
through
Reabsorption of Water and Urea
Removal from lumen
into ISF and capillaries
•
•
•
•
•
Na+, Cl- ,
65% water,
85 – 90% HCO3
100% glucose, amino acids
Other substances
 Concentration of
water in the lumen
Absorption
favoured by
Low HP
Water
reabsorbed by
osmosis into the
ISF and
capillaries
Colloidal
osmotic
Pressure
Tubular secretion
Some substances are removed (secreted)
- from blood through the peritubular capillary network
- into the distal convoluted tubules or collecting ducts.
- These include: H+ ions, K+, NH3 , creatinine, and drugs.
- H+ ions – secreted throughout the length of nephron tubule
(except thin loop of Henle);
- coupled with reabsorption of
- K+ - secreted at DCT and CT and CD;
- coupled with reabsorption of Na+
- NH3 - its secretion rate depends on acid-base equilibrium of
body fluid
- Urine is a collection of substances that have not been
reabsorbed during glomerular filtration or tubular secretion.
Tubular Transport Maximum (TM)
TM = Substances associated with membrane transporters
(carrier or active transport) for reabsorption have a
maximum rate at which they can be removed
– e.g. glucose
Renal threshold = the plasma concentration of a substance
when it first appears in the urine
- TM for the substance is exceeded its limit.
Renal threshold of gucose and diabetes mellitus
Deficient or
lack of insulin
1
Impaired movement of glucose
from plasma into body cells
Above
renal threshold
2
↑plasma concentration of
glucose
Glucose in the
tubules & urine
(Glucosurea)
↑ Plasma and tubular load
exceeds availability of carrier
3
molecules for glucose transport
and reabsorption
Renal threshold of gucose and diabetes mellitus
Glucose contributes
effective osmotic pressure
of the tubules
Osmotic diuresis
Water in the
tubules & hence
in the urine
↑ Volume of water
in the tubules &
hence in the urine
Frequent urination
Drink more water
Glycosuria (glucosuria): presence of glucose in urine
Polyuria: frequent urination
Polydipsia : increased thirst
Polyphagia : increased hunger
Renal counter-current mechanisms
1. Countercurrent multiplier system
2. Countercurrent exchanger system
Countercurrent multiplier system:
It is the process by which a progressively
increasing osmotic gradient is formed as a
result of countercurrent flow.
Parts involved in
countercurrent multiplier
system
1. Descending limb of loop of
Henle
2. Thin segment of ascending limb
3. Thick segment of ascending limb
4. Cortical collecting duct
5. Outer medullary collecting duct
6. Inner medullary collecting duct
Countercurrent multiplier
system
1
• Impermeable to solutes but
permeable to water
• Water diffuses by osmosis to
the higher osmotic pressure of
ISF
• Solute conc. (mainly NaCl)
increasing while approaching
hair-pin turn of loop of Henle
2
• Thin segment of ascending
limb – permeabe for NaCl but
impermeable to water
• Water remains in the tubule
and NaCl difuses (due to
concentration gradient) to ISF
Countercurrent multiplier
system
3
• Thick segment of ascending
limb – active transport of NaCl
to the ISF
• Water continues to be retained
• Osmolality of tubular fluid
entering descending limb is 300
mOsm/kg H2O
• Tubular fluid leaving ascending
limb and entering distal tubule
– diluted (osmolality 185
mOsm/kg H2O
Countercurrent multiplier
system
Vertical osmotic gradient in ISF
Is lower in outer medulla and
higher in inner medulla and
at hair-pin turn; established
and maintained by
a) continued active
transport of NaCl by thick
segment of ascending imb
b) conc of tubular fluid in
the descending limb
c) passive diffusion of NaCl
from the lumen of thin
segment of ascending limb
into the inner medullary ISF
Countercurrent exchanger system
– It is a countercurrent system in which transport between
inflow and outflow is entirely passive.
– Vasa recta
- is a countercurrent exchanger
- Permeable to water and solutes throughout their length
Countercurrent exchange in vasa recta
1. Blood enter with
300 mOsm/kg water
2. Descends through increasingly
hypertonic peritubular fluid
in medulla.
3. Water diffuses out.
Solutes diffuses in until
hair-pin turn is reached.
4. Blood then ascents through
decreasing hypertonicity and
water diffuses in and solute
diffuses out.
5. Blood returns to the cortex.
Milliosmolality is only slightly
higher than when it entered
Vasa recta.
Countercurrent exchanger system
In descending limb – water drawn by osmosis from vasa recta to ISF
(hyperosmotic created by countercurrent multiplier)
– Solutes diffuse from ISF to vasa recta
In ascending limb – solutes diffuse back into ISF
- Water is drawn by osmosis back into vasa recta
- The function of countercurrent exchange
- to retaine solutes in the ISF of medulla
- Increase rate of blood flow in vasa recta – reduce time for
diffusion of solute from ascending limb back to ISF – gradual loss
of solute from medulla – medullary washout
- This is prevented by low blood flow
- 10 to 20% of kidney blood flow
Role of urea
Urea
- Contributes high solute concentration in ISF
- Recirculation of urea assists countercurrent multiplier system
and osmotic gradient
- Urea excretion is maintained almost at the same level
whether the urine is dilute or concentrated.
Concentration of Urine
ADH and Osmoregualtion
- Epithelial cells of CT, CD – variable permeability depending on ADH
amount (Post Pit)
- ADH -  permeability of these cells for water
- ADH secretion - significant in 2% changes in plasma osmolality
- Degree of ECF dehydration – Osmoreceptor cells in hypothalmus
- Hyperosmolality -  secretion of ADH
- ADH acts on cortical and medullary CDs
-  water reabsorption
Thirst center in hypothalamus - also stimulated by hyperosmolality
Relationship among hypothalamus, posterior pituitary and
kidney in the regulation of extracellular dehydration
Control of hyperosmolality
Hypothalamus regulated
Thirst – predominant factor
for correction of
hyperosmolality
Diabetes insipidus
- Water is not reabsorbed in the CTs and CDs – excreted as urine
- Hypotonic tubular condition – absence or severely decreased
amount of ADH
- k/s diabetes insipidus
- Animal with this condition
- polyuria ( excess amount of water in urine)
- polydipsia (excessive thirst and excessive water intake)
- urine formed - dilute, lower than normal specific gravity
What are the differences between diabetes melitus and diabetes
insipidus
Diabetes insipidus and diabetes mellitus
What are the differences and similarities between diabetes
mellitus and diabetes insipidus
Particular
Diabetes insipidus
Diabetes mellitus
cause
Lack or deficient ADH
+ce of glucose in urine
Osmotic diuresis
-ce
+ce
Polyuria
+
+
Polydipsia
+
+
Thirst
+
+
Specificiific gravity
ow
High
Urine content
No glucose
glucose
Urine concentration
Normally • Urine concentration may vary depending on multiple factors
• In extreme cases in domestic animals
– urine-to-plasma osmolal ratio may approach (2400:300);
the urine concentration is 8 times that of plasma
• In desert rodents – urine-to-plasma ratio (16:1)
-- extreme adaption for body water conservation
-- water - not available; mostly gained water – metabolic
-- water loss minimized for survival
Renal failure and reduced urine concentration
Acute renal failure
- Normal : high O2 supply and high O2 use in renal tissue
- Persistently low renal perfusion (low renal blood supply as in
shock or renal damage) = decrease in GFR over hours or days =
causes acute renal failure
Chronic renal failure
- If renal failure (impaired GFR) remains for months
Renal failure and reduced urine concentration
Reduced urine concentration
Concentration failure
Mostly found in chronic renal diseases - ↓ concentrating ability
• More solute remained in functional nephrons
- contribute osmotic diuresis
• Hypertonicity in medullary ISF not maintained due to
- loss of medullary t/s or ↓ blood flow in the vasa recta
- ↓Na and Cl transport from the thick segament of
ascending limb of loop of Henlen
• Damage to cells in CTs and CDs – making less responsive to ADH