Term 2 Lecture 9: Reabsorption And Secretion Flashcards
Tubular reabsorption
(see diagram start of notebook 3)
1) lumina cell membrane
↓
2) the cytosol
↓
3) the basolateral cell membrane
↓
4) the interstitial fluid
↓
5) the capillary wall
Selective process
-Tubule wall is 1 cell thick and close to a surrounding peritubular capillary
- 5 barriers
- passive reabsorption- down electrochemical or osmotic gradient
- active reabsorption - against electrochemical gradient (glucose and Na+)
An active Na+ - K+ ATPase pump in the basolateral membrane is essential for Na+ reabsorption
(See diagram notebook 3)
80% of energy used in the kidneys is spent on Na+ transport
Na+ is reabsorbed along the length of the nephron tubule (but not in the descending limb of the l of H)
67% of it is from proximal tubule and is linked to reabsorption of glucose, amino acids, water, Cl- and urea
25% of it is from the ascending loop of Henle and is linked to production of concentrated urine
8% is in the distal and collecting tubules under hormone control and linked to long-term control of BP and connected to K+ secretion
Steps to transport Na+ back to the bloodstream and K+ into the kidney tubule for excretion
-intracellular Na+ concentration is low so passive movement of Na+ from the tubular lumen (where it’s high conc.) Into the tubular cell occurs
- basolateral pump then transports Na+ out of the tubular cell and into the lateral space
- Na+ symporter in the proximal tubule
-Na+ leak channels in the collective duct (inserted when more Na+ needs to be absorbed)
High concentration in lateral space (between tubular cells on interstitial side) so Na+ diffuses down concentration gradient into the interstitial fluid and into the peritubular capillary blood.
Cl- also flows down the concentration gradient created by active transportation of Na+. Where it passes between tubular cells (leaky right junctions)
Aldosterone stimulates Na+ reabsorption in the distal and collecting tubules
See diagram notebook 3
-a constant percentage of filtered Na+ is reabsorbed from the proximal tubule and loope of Henle regardless of Na+ load
- distal and collecting tubules Na+ reabsorption requires hormonal control
- discretionary reabsorption is related to Na+ load - if theres too much Na+ a smaller fraction is reabsorbed and excess Na+ is excreted
Aldosterone promoted Na+ reabsorption in response to circulating Aldosterone ll acting on the adrenal cortex
Renin angiosterone-aldosterone systems
= RAAS
If you drink only water and eat no food for a long period of time
You’d have a low Na+ level in your body. The hormone aldosterone will be produced and mechanisms within the tubule will allow insertion of leaky channels into the distal region to reabsorb more Na+
Production of aldosterone is under the control of RAAS (which is also linked to BP regulation)
RAAS precisely regulates Na+ by inserting leaky channels into the luminal side of the distal and collecting tubule cells
Distal collecting tubules contain 2 different kinds of tubule cell
1) intercalated - linked to acid-base balance
2) principal- where channels are inserted by aldosterone for Na+/K+ transport
& by vasopressin for water transport
Vasopressin aka anti-diuretic hormone
Function of RAAS (renin angiotensin-aldosterone systems)
Angiotensinogen is an inactive precursor produced by the liver and always in blood circulation.
If your Na+ level is low this is sensed by the macula densa cells and they release renin.
This cleaves angiotensinogen converting it to angiotensin l
Angiotensin 1 is converted to the active angiotensin 2 by angiotensin converter enzyme (ACE) produced by the lungs.
Angiotensin ll acts on the adrenal cortex
Stimulating production of aldosterone.
Aldosterone then stimulates the principal cells to insert Na+ leaky channels into their luminal membranes.
Leaky channels cause more Na+ reabsorption from distal filtrate back into the blood stream
So if Na+ levels are low RAAS is active.
If your Na+ load is high the RAAS mechanism is less active, less aldosterone is secreted and excess Na+ is excreted
Angiotensin ll is also involved in BP regulation
It acts on the sympathetic nerves in the arteries causing them to constrict, raising BP and also causing central activation of neurones in the brain to induce thirst to make you drink and also to make you produce vasopressin.
All of these mechanisms feedback to raise BP and change blood volume
Individuals with high BP
Caused by hypertension or heart failure following a heart attack.
They have disregulated angiotensin ll - it is upregulated causing angiotensin ll to be produced when it is not needed.
This stimulates aldosterone production and leaky channel insertion causing more Na+ reabsorption when it is not required.
Hypertension can be treated by diuretics such as furosemide which block reabsorption of Na+ in the loop of Henle. Within 15 mins of taking this diuretic the individual will produce lots of urine lowering blood volume and therefore decreasing BP
It can also be treated by ACE inhibitors such as captopril- these stop the conversion of angiotensin l to the active form angiotensin ll.
Or with aldosterone antagonists such as spironolactone that can be used to prevent aldosterone secretion.
All of these drugs prevent the kidney from doing its job of reabsorbing Na+ which has a huge impact on cardiovascular regulation
These medicines also work on other mammals such as cats and dogs.
Natriuretic peptides inhibit Na+ reabsorption
RAAS renal handling of Na+ causes Na+ retention and raises BP
Natriuretic peptide hormones cause Na+ loss and lower BP
(See diagram notebook 3)
ANP - atrial natriuretic peptide is present in the atrial cardiac muscle cells
BNP- brain natriuretic peptide is present in the ventricular cardiac muscle cells
Both these peptides are stored in granular form and released by mechanical stretching of the heart.
Expansion of circulatory volume occurs when ECF (extracellular fluid) is increased
Na+ and H2O retention increase BP
NPs promote natriuresis and accompanying diuresis, decreasing the plasma volume and directly influencing the CVS to lower BP
How NPs function
They directly inhibit Na+ reabsorption in the distal parts of the nephron.
Inhibit renin secretion from the macula densa (in the kidneys)
Inhibit aldosterone secretion from the adrenal cortex
Inhibit secretion and action of vasopressin
Also they cause the afferent arteriole to vasodilate and efferent arteriole to constrict - increasing GFR causing increased excretion
How NPs increase excretion
They relax the glomerular mesengial cells to increase Kf (widening membrane holes)
ANP is more effective than BNP
they cause increased Na+ and accompanying osmotic H2O excretion in urine.
Indirectly lowering BP
Reduced Na+ and fluid load
Reduced CO
They also reduce peripheral vascular resistance by inhibiting SNS activity to the heart and blood vessels.
The effects of ANP and BNP in cardiovascular disease is a subject of much research.
Could long-term hypertension be related to ANP-BNP mechanism?
The research may lead to development of new drugs for hypertension
Glucose and aas are reabsorbed by Na+ dependent secondary active transport
1) Na+ moves down the electrochemical gradient into the proximal tubule cells via secondary active transporter SGLT. The SGLT cotransporter pulls glucose in against the concentration gradient.
2) Glucose diffuses out of the basolateral side of the cell via facilitated diffusion carrier channel protein GLUT
3) Na+ is pumped out of the proximal tubule cells via Na+-K+ ATPase
SGLT= sodium glucose cotransporter
GLUT= carrier glucose transporter
Proximal tubule: secondary active transport symport carries sodium and glucose cotransporter (SGLT) which allows passive Na+ transfer across luminal membrane and basolateral pump pumps Na+ through into the lateral space
The SGLT pulls glucose through the symport against the concentration gradient. Glucose then passively diffuses down the concentration gradient across the basolateral membrane into the plasma facilitating GLUT
Some urea is also reabsorbed
Urea in the bloodstream helps to maintain osmolarity of the blood plasma
