L5 - 6 - Renal Reabsorbation and Secretation

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Define tubular reabsorption,

Identify and describe


tubular secretion, Describe tubular secretion
mechanism involved in
transcellular and paracellular with PAH transport and K+
Glucose reabsorption
transport.

Identify and describe Identify and describe the


Study glucose titration curve
mechanisms of tubular characteristic of loop of
in terms of renal threshold,
transport & Henle, distal convoluted
tubular transport maximum,
Describe tubular reabsorption tubule and collecting ducts
splay, excretion and filtration
of sodium and water for reabsorption and secretion

Identify the tubular site and Identify the site and describe
Revise tubule-glomerular
describe how Amino Acids, the influence of aldosterone
feedback and describe its
HCO3-, P04- and Urea are on reabsorption of Na+ in the
physiological importance
reabsorbed late distal tubules.
Mind Map
As the glomerular filtrate enters the renal tubules,
it flows sequentially through the successive parts
of the tubule:
The proximal tubule → the loop of Henle(1) →
the distal tubule(2) → the collecting tubule →
finally ,the collecting duct, before it is excreted as
urine.

A long this course, some substances are


selectively reabsorbed from the tubules back into
the blood, whereas others are secreted from the
blood into the tubular lumen.

The urine represent the sum of three basic renal


processes: glomerular filtration, tubular
reabsorption, and tubular secretion:

Urinary excretion = Glomerular Filtration –


Tubular reabsorption + Tubular secretion
Mechanisms of cellular transport in the nephron are:

Active transport Pinocytosis\


Passive Transport Osmosis
“Active transport can move a solute exocytosis
against an electrochemical gradient and
requires energy derived from
metabolism”
Water is always
reabsorbed by a
Simple diffusion passive (nonactive) (Additional reading)
Primary active Secondary active (without carrier physical mechanism
The proximal tubule, reabsorb
protein) called osmosis ,
transport transport large molecules such as
Cl, HCO3-, urea , which means water proteins by pinocytosis. In this
Transport that is creatinine diffusion from a region process, the protein attaches to
Transport that is of low solute the brush border of the luminal
coupled directly to coupled indirectly to an concentration (high membrane, then invaginates to
an energy source energy source due to the interior of the cell until it is
water concentration)
such as ATP concentration gradient completely pinched off and a
to vesicle is formed containing the
of ion one of high solute protein. Once inside the cell
Facilitated concentration (low the protein is digested into its
Sodium-potassium
pump
diffusion water concentration). constituent amino acids, which
are reabsorbed through the
Na-K-2Cl co-transport (require carrier basolateral membrane into the
protein) interstitial fluid. Because
(found in basolateral pinocytosis requires energy, it is
membrane along renal glucose-sodium co- Glucose and amino considered a form of active
tubules) transport (SGLT) acids at the transport.
basalateral border
(GLUT)
amino acid-sodium co-
transport
(1) Co-transport : movement of two molecules in the same direction
H+-pump but they opposite in concentration gradient
H+/Na counter-
transport
(2) Counter-transport: movement of two molecules in opposite direction
based on their concentration gradient
The ways of transport:
1- From lumen of tubules (Apical membrane”1”) to epithelial cells Second, through the First, Reabsorption of
then from epithelial cells to interstitium (Basolateral membrane): renal interstitium , and filtered water and solutes
A-Transcellular route: (through the cell membrane) back into the blood from the tubular lumen
B-Paracellular route: (between spaces of tight cell junction) through the Peritubular across the tubular
capillary membrane epithelial cells
2- From interstitium (basolateral space) to the Peritubular
capillaries: By ultrafiltration (bulk flow) that is mediated by:
hydrostatic and colloid osmotic forces

(1) Apical membrane = brush border which is numerous to help in reabsorbation


1. :
A. Sodium diffuses across the luminal membrane
(also called the apical membrane) into the cell
down an electrochemical gradient (with other
substances such as glucose, amino acids etc.)
established by the sodium -potassium ATPase
pump on the basolateral side of the membrane.
B. Other molecules like water and Cl , Ca etc. by
osmosis and diffusion

2. :
A. Sodium is transported across the basolateral
membrane against an electrochemical gradient by the
sodium -potassium ATPase pump
B. other substances will across the basolateral
membrane by passive diffusion

3. Sodium , water , and other substances are


reabsorbed from the interstitial fluid into the
Peritubular capillaries by ultrafiltration (bulk flow ”1”),
a passive process driven by the hydrostatic and colloid (1) Bulk flow = movement of water with other substances
While diffusion = movement of substances without water.
osmotic pressure gradients
In Peritubular capillaries the high plasma
oncotic pressure is due to fluid filtration in
glomerulus

increase GFR  increase oncotic pressure &


decrease hydrostatic pressure in efferent &
Peritubular capillaries  increase bulk flow
from lateral space to Peritubular capillaries
 increse reabsorption

decrease GFR  decrease oncotic pressure &


increase hydrostatic pressure  decrease
bulk flow  fluid go back to lumen through
tight junction  decrease reabsorption
1- Responsible for producing a
concentrated urine in the medulla.

2- When ADH (antidiuretic hormone) is


1- Proximal tubules is coarse adjustment
present, water is reabsorbed and urine is
(reabsorption a most of of water and
concentrated.
solutes)
Descending limb: (concentrate urine ”1”)
3-100% of glucose and amino acids 1- water permeable and allow
reabsorbed absorption of 25% of filtered H2O.
2-It is impermeable to Na-CL.
2- Solute reabsorption in the proximal 3-fluid become hyper-osmolar
tubule is isosmotic (equal amount of
Thin ascending limb: (dilute urine ”2”)
solute and water are reabsorbed)
1- impermeable to H2O
2- permeable to NaCl (passive)
3-By the end of ascending limb of loop,
(1) Concentrate urine = remove water from fluid
the tubular fluid becomes hypo-osmolar
(2) Dilute urine = remove solutes from urine Thick ascending limb: (dilute urine)
1- impermeable to H2O
* The main function of tubules is concentrate urine 2- Na-K-2Cl co-transport occur in this
and that has done in loop of henle of Juxtamedullary nephron part. (active)
3-the tubular fluid becomes hypo-
* Sodium-potassium pump that found in
osmolar to plasma in this part
distal convoluted tubules is under control of aldosterone
1- Distal tubule is fine adjustment
(reabsorption a fine amount of water and solutes by
1- Composed of two types of cells:
hormonal control based on body needs)
a. Principal cells: absorb Na+& H2O and secrete K+
b. Intercalated cells: absorb K+ & secrete H+
2- The first portion of DCT forms part of
Juxtaglomerular Apparatus, that provides feedback •Secretion of K+ and reabsorption of Na+ controlled
control of GFR and RBF of the same nephron. by aldosterone.
2- water permeability under ADH control. (works
3-The next early portion has the same characteristics
under body needs)
as ascending limb of Henle that is
1-impermeable to water 3- Impermeable to Urea.
2-absorbs solutes.
So it is called the diluting segment & the osmotic
pressure of the fluid ~ 100 mOsm/L.

1- Under ADH control. (works under body needs)


2- Highly permeable to urea.
3- Final site for processing urine.
4- Secretes H+ helps to:
a- maintain blood pH
b- reabsorb HCO3 and generate new HCO3
Reabsorbation Secretion
- Poorly reabsorbed of creatinine and urea
- 60% - 75% of sodium and water - H+
Proximal convoluted tubules - 90% of HCO3, K+, Ca and Cl- - Urea
- 100% Glucose and amino acids - ammonia

Descending loop of henle -25% of water (H2O) __________________

Thin ascending loop of henle - Sodium chloride (NaCl) __________________

- Sodium
Thick ascending loop of henle - Potassium __________________
- Chloride

- Sodium in response to aldosterone


- Potassium in response of aldosterone
Distal convoluted tubules - Water in response of ADH
- Calcium in response of parathyroid hormone

a. Principal cells: absorb Sodium Na+ & H2O


b. Intercalated cells: absorb Potassium K+ & HCO3 a. Principal cells: secert K+
Late distal tubule & Cortical
-Water in response of ADH b. Intercalated cells: secret H+
Collecting ducts - Sodium in response to aldosterone Potassium in response of aldosterone
- Calcium in response of parathyroid hormone

-Water in response of ADH


Medullary Collecting ducts - Highly permeable to urea ( to maintain osmolarity of - H+
medulla )
Site Between Functions
Primary Active Transport
Sodium-potassium Reabsorbation of sodium and secrete potassium to maintain
pump
All renal tubules Basolateral membrane
the intracellular and extracellular balance of Na and K

Secondary Active Transport


H+/Na counter- Proximal convoluted tubules, Distal Reabsorbation of sodium and secrete hydrogen ion and It is
Apical membrane
transport convoluted tubules and collecting ducts coupled with bicarbonate transport
Proximal convoluted tubules, Late
HCO3/Na co-transport distal convoluted tubules and collecting Basolateral membrane Reabsorbation of sodium and bicarbonate
ducts
Reabsorbation of sodium, potassium and two chloride to
Na-K-2Cl co-transport Thick ascending limb of henle’s loop Apical membrane
dilute water
glucose-sodium co-
transport (SGLT)
Proximal convoluted tubules Apical membrane Reabsorbation of sodium and glucose

Amino acid-sodium co-


transport
Proximal convoluted tubules Apical membrane Reabsorbation of sodium and amino acid

Simple diffusion
Passive NaCl transport Thin ascending limb of henle’s loop Apical membrane Reabsorbation of NaCl to dilute fluid in tubules
Passive channels of K+ , Apical membrane &
All renal tubules Reabsorbation and secretion
Cl , Ca etc. Basolateral membrane
Facilitated diffusion
Glucose transporter
(GLUT)
Proximal convoluted tubules Basolateral membrane Reabsorbation of glucose to interstitial fluid

Osmosis
All renal tubules except:
Apical membrane &
Water 1- thin and thick ascending limp and Reabsorbation of water
Basolateral membrane
2- early portion of distal convoluted tubules
• Essentially all glucose is reabsorbed

• The renal threshold for glucose= 180 mg/dl


• Glucose inter the tubular cells by secondary active transport
“co-transport”, It use SGLT “a specific transport protein
• the tubular transport maximum for glucose
“which needs Na” .
Tmg = 375 mg/min in men and 300 mg/min in
women.
• Then it’s cross the cell membrane into the interstitial spaces
by facilitated transport “passive transport” which use
GLUT’s “do not need Na” .

• Glucose reabsorption occur in proximal tubule . What is the difference between renal threshold
and tubular transport maximum ?

Renal threshold : it’s the rate that glucose begins


What cause the excretion of glucose in urine to appear in the urine .
before reach to its maximum transport? transport maximum for glucose : all nephrons
have reached their maximal capacity to reabsorb
glucose “maximum saturation of transporters”
not all nephrons have the same transport
maximum for glucose, and some of the
nephrons therefore begin to excrete glucose
before others have reached their transport
maximum
• First of all, bicarbonate (HCO3-) attaches itself
with hydrogen (H+) then it becomes H2CO3 in
1 the lumen

• Carbonic Anhydrase will break H2CO3 down to


water (H2O) + carbonic dioxide (CO2) which
2 diffuses into the proximal tubule

• Carbonic Anhydrase will convert the water


3 (H2O) + the carbon dioxide (CO2) to HCO3- + H+

• Hydrogen will transport out and sodium (Na)


4 will come in the proximal tubule

• Lastly, the HCO3- will go into the blood


5
Relations among the filtered load of glucose, the rate of glucose reabsorption by the renal
tubules, and the rate of glucose excretion in the urine
There must be a balance between tubular reabsorption and glomerular filtration.
This is controlled by local , nervous & hormonal mechanisms.

1.Glomerulotubular balance: prevents overloading of 5-Tubuloglomerular feedback: it will observe


distal parts when GFR increases. concentration of sodium chloride by macula dense in
distal tubules and what will lead to:
1- constriction and dilatation of afferent arteriole which
affect on GFR
2. Peritubular capillary reabsorption is regulated by 2- release renin which increase reabsorabtion of sodium
hydrostatic and colloidal pressures through the and play a role in production of angiotensin II
capillaries.

6-Hormonal:
- Angiotensin II : release aldosterone
3. Arterial blood pressure: if increased it reduces - ADH : H2O reabsorbation
tubular reabsorption. (increase in blood pressure will
reduced GFR in response of myogenic mechanism and
- ANP : Sodium excretion and diuresis
the decrease reabsorbation) Parathyroid hormone: Increases Ca
reabsorption & decreases phosphate
reabsorption
4. Nervous Sympathetic:
(1) ADH: Antidiuretic hormone
-Increases Na+ reabsorption.
(2) ANP: atrial nitric peptide
(3) Diuresis: increase urine output
Function
• 1-increases Sodium reabsorption
• 2-stimulates Potassium secretion
When does it secreted?
• (1) Increased extracellular potassium concentration.
• (2) Increased angiotensin II levels, which typically occur in conditions associated with sodium and
volume depletion or low blood pressure (so it will increase blood pressure)
Site of secretion
• Aldosterone, secreted by the zona glomerulosa cells of the adrenal cortex.

Mechanism of action
• by stimulating the sodium-potassium ATPase pump on the basolateral side of the cortical collecting
tubule membrane.
• Aldosterone also increases the sodium permeability of the luminal side of the membrane .
Diseases associated with aldosterone
• Absence of aldosterone, as occurs with adrenal destruction or malfunction (Addison’s disease)
• Excess aldosterone, as occurs in patients with adrenal tumors (Conn’s syndrome) is associated with:
1- sodium retention 2- decreased plasma potassium concentration
• Absorption throw apical
Proximal tubules:
membrane is done 1- has the greatest
passively. effect in all tubules. Distal tubules:
2- the fluid inside it is
• Movement of Na throw isosmotic.
1- Has mucla densa which
is Na sensitive + excretes
basal membrane is done renin.
Na/K ATPase. 2- has principal cell: Na +
H2o absorption & K
• ↑ GFR → ↑ Absorption secretion
3- has intercalated cell:
absorbs K and secretes H+
• Sympathetic → ↑ Na (controls pH)
Loop of Hele:
absorption * Descending: concentrate
urine by reabsorption of water.
* Thin ascending: Absorbed Na
• ADH → ↑ H2O absorption Cl
* Thick ascending: Absorbed
Na 2Cl K
• Aldosterone → ↑ Na
absorption + K excretion

• ANP ↑ Na excretion
Ans: 1-C, 2-B, 3-D, 4-C, 5-A, 6-B, 7-C. 8-A,
Q1: One of these examples is control passively: Q5: Most of filtered water is reabsorbed in:
A/Transport maximum A/ Proximal convoluted tubule (PCT)
B/Transcellular reabsorption B/Distal convoluted tubule (DCT)
C/Paracellular reabsorption C/Ascending loop of henle
D/co-transport D/Descending loop of henle

Q2: where is Sodium-potassium specific pumps? Q6: Glucose reabsorption is the difference between:
A/Basement membrane A/the amount of glucose filtered and the amount Secreted
B/Basolateral membrane B/the amount of glucose filtered and the amount excreted.
C/Interstitial wall C/the amount of glucose reabsorbed and the amount excreted.
D/Cytoplasmic membrane D/the amount of glucose reabsorbed and the amount secreted

Q3: Where can you found sodium-potassium pump? In Q7: When plasma glucose reach which called “glucose renal
between.. threshold” , How much is glucose level in vein that will lead to
A/Tubular lumen & tubular cell. appear in urine ?
B/Iinterstitial fluid & tubular lumen. A/250mg/dl
C/ interstitial fluid, tubular cell & tubular lumen. B/375 mg/dl
D/interstitial fluid & tubular cell C/180mg/dl
D/200mg/dl
Q4: When 3 Na / 2 K pumped in Basolateral
membrane, the net result is: Q8: How much is maximum absorptive capacity for glucose in
A/High intracellular Na concentration men?
B/Low Extracellular Na concentration A/375mg/min
C/ osmolarity in the basolateral space B/200mg/dl
D/osmolarity in the basolateral space. C/250mg/min
D/300mg/min
Ans: 9-B, 10-B, 11-D, 12-D, 13-B, 14-C, 15-D.
Q9: Amino acid is reabsorbed in Basolateral membrane by : Q13: Which of the following is an site of NaCl
A/ATP diffuses passively ?
B/ Diffusion A/Proximal convoluted tubule (PCT).
C/ Co-transport with Na B/ thin ascending loop.
D/Na+/K+ ATPase C/ Distal convoluted tubule (DCT ).
D/ thick ascending limb .
Q10: What is the main important mechanism for Na
exchange on Bicarbonate reabsorption ? Q14: the amount of water, solute reabsorption and
A/Reabsorpetion of HCO3 secretion depends on :
B/Secreted H+ A/Age
C/Diffuses CO2 B/Wight
D/Filtered HCO3 C/ body’s needs
D/secrete H+
Q11: At the end of descending loop of henle the osmolarity
will be : Q15: During Reabsorption/secretion of H2O in Late
A/Decrease Distal Tubules and Collecting Tubules, the H2O is
B/No change more dependent on :
C/Minimal change A/Angiotensin II
D/Increase B/principal cells
C/Aldosterone
Q12: Which site has a high permeability of water: D/Anti-Diuretic hormone
A/Thick ascending loop of henle
B/Thin ascending loop of henle
C/Early portion of Distal convoluted tubule
D/Thin descending loop of henle

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