Wk 27 Flashcards
Where is Na+ and Cl- reabsorbed the most?
Proximal tubule
Tubule reabsorption takes place by both transcellular and paracellular pathways.
What is transcellular? =
What is paracellular?=
Trans is through the cell via sodium channels and coupled cotransporters and exchangers
Paracellular is between epithelial cells via tight junctions
What does Na+ reabsorption involve? (The different channels and transporters)
Apical transporters
Epithelial sodium channels
Basolateral Na-K pump
Na-H exchanger
Electrogenic Na/HCO3 cotransporter
Balance between paracellular and transcellular absorption along the tubular system depends on what?
The electrochemical gradient at that level
How does regulation of Na+ absorption happen? (Glomerulotubular balance)
If the glomerulus lets too much Na through, the tubules increase their reabsorption rate to stablize the filtered amount
How does Angiotensin II work in the nephron?
related to Na
Binds to AT1 receptors at the apical and basolateral membranes of proximal tubule cells= PROMOTE Na+ REBSORPTION INTO BLOOD (so water will follow and you pee out less water)
How does aldosterone work in the kidney?
related to Na
Stimulates Na+ reabsorption by the Collecting Duct (Initial collecting tubule, cortical collecting tubule and medullary collecting ducts)
How does sympathetic nerve stimulation act on the nephron?
related to Na
Decreases renal blood flow and GFR which means less Na+ excretion into urine
ALSO, alpha adrenoceptors on proximal tubules increase Na+ reabsorption
(you want to keep Na so your BP stays high in fight or flight)
How does arginine vasopressin (antidiuretic hormone) affect water excretion from kidneys?
It stimulates the retention of water and very concentrated urine (with hardly any water in it)
How does atrial natriuretic peptide affect sodium levels in the nephron?
It promotes natriuresis (sodium secretion in urine) due to increasing blood flow to nephrons and also direct effects on collecting duct
If GFR increases, what happens to reabsorption?
Increases proportionally (this is Glomerulotubular [GT} balance)
What is the major substance the kidneys filter and then totally reabsorb?
What is the major substance the kidneys filter, reabsorb and secrete?
Glucose
Urea
Where is glucose reabsobed in the nephron and by what 2 mechanisms?
Proximal convoluted tubule
Apical, electrogenic Na/Glucose cotransporter and a basolateral facilitated diffusion mechanism
Where is phosphate reabsobed in the nephron and by what mechanism?
Proximal convoluted tubule reabsorbs most
Via Na/ Phosphate cotransporter
Where is calcium reabsorbed in the nephron and how much of the filtered amount is reabsorbed?
Proximal convoluted tubule
99% is absorbed back into blood
Where does most magnesium absorbed in nephron?
Thick ascending limb of Henle’s loop
Where are amino acids absorbed?
Proximal tubule (using many transporters on apical and basolateral membranes of epithelial cells)
Where is potassium reabsorbed and secreted in the nephron?
Proximal tubule reabsorbs most of the filtered K and the distal tubule may reabsorb or secrete K depending on level in body
(When someone has high K, the collecting duct secretes K into lumen for excretion = called the distal K + secretory system)
What does the renal excretion rate (EX) depend on? (3 factors)
- rate of filtration of X (FX)
- rate of reabsorption of X (RX) by tubules
- rate of secretion of X (SX) by tubules
How do you estimate the net amount reabsorbed or secreted by the renal tubules and why is this important?
By measuring the difference between the amount of X filtered with the amount of X excreted into urine
Important so you can understand how glomerular filtration, tubule reabsorption and tubular secretion is working
(can’t provide info on specific sites though)
What are the limitations with using clearance methods to estimate overall nephron function?
They can’t provide any information on exact sites and mechanisms of transport
The only route of entry to the kidney is the _____
The only 2 routes of exit are the _____ and the ______
Renal artery
Renal vein and ureter
(therefore input of X equals output of X because solutes come in and either stay in blood [renal vein] or are excreted in the urine [ureter])
The clearance equation describes?
The volume of plasma that would be totally cleared of solute X in a given time
What 3 things do we need to know to work out the clearance of solute X?
- The conc of X in the blood plasma (Px)
- The volume of urine formed in a given time (V)
- The concentration of X in the urine (Ux)
What special solute’s clearance is a good estimation of RPF (renal plasma flow)?
(and why?)
p-aminohippurate (PAH)
because it is cleared completely from the plasma by the nephron
What solute is used to estimate GFR?
And why?
Inulin
Because it is freely filtered through the glomerulus and not reabsorbed into the blood or secreted from the blood in the tubules at all- the amount of inulin in the urine is the same amount that gets filtered by the glomerulus)
What is an endogenous compound that is used to assess GFR?
Why?
Creatinine
Because it is produced at a constant rate by the muscles and is almost completely filtered at the glomerulus and is not reabsorbed or really secreted
When there is a low circulating blood vol, what 4 pathways are triggered?
What do they all lead to?
- Increase in Renin
- The barroreceptors in the kidney notice a decreased GFR so the juxtaglomerular apparatus secretes renin= angiotensin= aldosterone) - Increase in Sympathetic NS
- The brain gets signals from everywhere (heart, liver, lungs, etc) so symp activity is increased - Posterior pituitary stimulation
- Again, the brain gets lots of signals and tells posterior pituitary to secrete ADH so less water is excreted - Decreased release of Atrial natriuretic peptide (ANP)
- The heart atriums notice drop in blood vol and so the atrial myocytes stop producing ANP
The end result is less sodium (and therefore water) excreted in the urine and more retained in the blood
What substances are important determinants of osmolarity? (3)
Urea and sodium chloride
We usually consume way more protein than we need so the rest is broken down by the liver, resulting in large amounts of urea
Urea is freely filtered by the kidney, usually solutes excreted in such large amounts would draw large amounts of water into the urine (causing osmotic diuresis) but urea doesn’t, why is this? (2 reasons)
Because there are specialised urea transporters that allow large amounts of urea to be excreted without water following it
Also Anti Diuretic Hormone somehow allows urea to be excreted without water excretion
Where are the primary sites for urea reabsorption?
Where are the primary sites for secretion?
Proximal tubule and the medullary collecting duct
Thin limbs of the loop of Henle
Out of creatinine and urea, what is the more accurate assessment of renal function, but what is increased earlier (in the serum) in renal disease?
What ratio is often used to assess renal function?
Creatinine is more accurate because urea can increase and drop depending on diet, how the liver is working etc while creatinine stays stable
Serum urea is increased earlier in renal disease
Creatinine to urea ratio
Does drinking a whole heap of water mean more solutes are excreted too with the excess water?
No, there are mechanisms that keep solute secretion constant no matter the water intake
How does the kidney generate dilute urine?
It pumps salts out of the lumen of the tubule, back into the blood so the fluid that is left is hypo-osmotic (dilute)
How does the kidney produce concentrated urine?
Uses osmosis to drive water out of the tubules by making the interstitial fluid very hypertonic so water is dragged out of the lumen
Does osmolality increase or decrease as you go from the cortex of the kidney to the outer and then inner medulla?
Increases
How does ADH work to make either dilute or concentrated urine (v simple explanation)
Dehydration= ADH is released if there is increased osmolality in extraceular fluid and it acts on the collecting tubules to reabsorb more water so there is concentrated urine
Too much water= The release of ADH is stopped if there is a decreased osmolality in the extracellular fluid so the collecting tubules don’t reabsorb water and it is excreted in urine to make dilute urine
What is the effect of Aldosterone on NaCl reabsorption?
Increases NaCl reabsorption (so increases water reabsorption too)
What is the effect of Angiotensin II on NaCl reabsorption?
Increases NaCl reabsorption and also increases water reabsorption
What is the effect of Atrial Natriuretic Peptide on NaCl reabsorption?
It is released when the heart atria are stretched (hypertention) so it decreases NaCl reabsorption and therefore decreases water reabsorption (decreasing BP)
Where are the sensors that sense blood pressure?
Aortic arch
Carotid sinus
Renal afferent arteriole
Atria
What are the 4 efferent pathways that regulate BP?
RAAS
Symp NS (vasoconstriction of afferent arterioles)
Atrial Natriuretic Peptide
Anti Diuretic Hormone
What is the effector and what is affected in the regulation of BP….
Short term?
Long term?
Short term= Heart, blood vessels (blood pressure)
Long term= kidneys (Na+ retention and excretion)
An increased arterial pressure increases urine output by ______ ______
Pressure diuresis
only a slight increase in BP is enough to raise urinary excretion by a lot
A slight change in blood vol causes a big change in _____ ____
A slight change in that causes a big change in ___ _____
A slight change in that causes a big change in ____ ______
These factors work together to provide effective feedback control of blood vol
Cardiac output
Blood pressure
Urine output
___receptors in the hypothalamus release ___ ________ (also known as ____ ____ ____) from the pituitary and promote thirst (to increase water intake and increase BP)
Osmoreceptors
Arginine Vasopressin (Anti diuretic hormone)
What are the 2 classes of humoral controls that influence the circulation?
Vasoactive substances (act on blood vessels)
Nonvasoactive substances (act on targets other than the cardiovascular system)
What are the 5 main humoural vasoconstrictors?
Adrenalin (on alpha 1 receptors)
Serotonin (5HT)
Angiotensin II
Anti-diuretic hormone (AVP)
Endothelin
What are the 6 main humoral vasodilators?
Adrenalin (B2 receptors)
Histamine
Atrial natriuretic peptide
Bradykinins
Prostaglandins
Nitric Oxide
What tubule runs adjacent to the afferent and efferent arterioles in the nephron?
The thick ascending limb of the loop of Henle (as it transitions into the distal convoluted tubule)
Where the thick ascending limb of loop of henle and the afferent/ efferent arterioles meet, they form the monitoring structure called the _______ ______ ________ (_ _ _) which is composed of _____ ____ cells and _______ _________ cells
Juxtaglomerular apparatus (JGA)
Macula densa cells and JG cells
When blood pressure drops, what cells sense the BP drop and what cells release renin?
Macula densa cells sense the drop in blood pressure and tell the juxtaglomerular cells (granular cells) to release renin
What does angiotensin II do?
Constricts arterial smooth muscle and promotes sodium and water retention (also converts to aldosterone which also increases sodium and water retention)
