Renal physiology Flashcards
What does urinary excretion allows us to remove?
Excess:
- water
- electrolytes
- metabolic waste products
- How does the kidney form urine?
> Why does the kidney receive a large % of cardiac output?
- Filtering the blood > in Renal cortex
> The Kidney receives a disproportionately large blood flow 0.5-1% of body mass 20-25% of cardiac output > earliest supplied organ as it is directly supplied by the descending abdominal aorta.
Blood in the kidney is directed to the renal cortex what happens to the vessels?
The renal cortex is the site of what process..
- Vessels subdivides into a network of capillary loops….Glomerulus
> site of blood ultrafiltration
What surrounds the Glomerulus?
What is the significance of the Glomerulus having a complex structure?
- Enveloped by a layer of epithelial cells called the Bowman’s Capsule
> The filtrate is collected into the tubular epithelium of the nephron - Complex structure makes it harder for blood to flow through→ slower flow → Gives more time for filtration to occur.
What kind of circulation does the Glomerulus have?
- Dual circulatory system - Has two capillary beds (glomerula and peritubular capillary beds) and two arterioles (afferent and efferent)
Define Glomerular filtration rate?
What is the equation?
- The rate of fluid filtration from the renal capillaries into the Bowman’s space
> GFR = Kf * [(PGC – PBS) - σ(πGC – πBS)]
Kf = Filtration Coefficient
(the permeability of the capillary to water)
σ = Reflection Coefficient
(how impermeable the capillary is to proteins)
What is the typical Glomerular filtration rate?
What does this allow?
- 125mL/min
> High filtration rate allows toxic metabolic waste products to be swiftly excreted, and prevents them accumulating within the extracellular fluid
The rate of formation of interstitial fluid in the rest of the systemic circulation is about 20 L/day, whilst receiving 75% of the cardiac output.
Whilst the Kidney filters 180 L/day into the nephron whilst receiving only 25% of the cardiac output
Why is the filtration rate so much greater from the glomerular capillaries than from systemic capillaries?
- A higher glomerular capillary pressure is present due to its knotted structure which creates more resistance and thus creates a higher blood pressure within the glomerular capillary partly due to it getting a higher blood flow than it requires (25% of cardiac output despite being 1% of body mass).
- Filtration coefficient is much higher as the glomerular capillaries are more permeable to water than the capillaries in systemic circulation
What are the 2 autoregulatory mechanisms they kidney has to ensure that GFR stays constant
1- Myogenic response of the afferent arteriole - Changes in arterial blood pressure directly triggers afferent arteriolar constriction/dilatation
2- Tubuloglomerular feedback - Nephron sends paracrine messenger to elicit arteriolar constriction/dilatation in response to a fall in GFR
> Autoregulation of renal blood flow enhances PGC (glomerular capillary hydrostatic pressure) stays constant in face of alterations in arterial blood pressure
Describe the different capillary structure in the kidney compared to the systemic circulation.
What is the primary cause of high filtration rate?
- The kidney has fenestrated capillaries compared to the continuous capillaries found in the vast majority of the systemic circulation
- Increased Filtration coefficient (Kf) is the primary cause of this high filtration rate.
> double arteriolar system also helps keep blood pressure higher in glomerular capillaries than system capillaries
- What is the problem with having fenestrated capillaries in the kidney?
- What solves this problem and prevents proteins from moving through the fenestra?
- There are spaces large enough to allow proteins and cells to crossing into the nephron
- Podocytes: Podocytes wrap around the glomerular capillaries to create a barrier which prevents filtration of cells and proteins.
- Basement membrane: Helps select what can cross the filtration barrier based upon molecular weight and electrical charge…. Negatively charged proteins are repelled by the highly negatively-charged basement membrane.. >70 kilodaltons cannot cross
1- What is the molecular weight of albumin? What stops it from crossing Basement membrane?
2- What is Minimal change disease?
1- 69 kilodaltons
> Glycocalyx formed by the basement membrane and the podocytes means that the basement membrane is heavily negatively charged which repels proteins.
2- Kidney disease characterised by proteins getting into the urea where the basement membrane has lost its negative charge.
1- We have 1million nephrons, What is the function of a nephron?
2- On average what volume of filtrate will a nephron handle? - Why does the nephron deal with such a small volume of filtrate?
3- Describe the flow of blood through nephron.
1- Tubular epithelium of each segment of the nephron is specialised to facilitate uptake of specific components of the filtrate - SELECTIVE REABSORBTION
2- 90 µL of filtrate a day - easier to selectively reabsorb substances as its easier to change concentration in small volumes, a lot of control over the final urinary output.
3- Proximal convoluted tubule → Thin descending limb of Henle’s loop →Thin ascending limb of Henle’s loop →Thick ascending limb →Distal convoluted tubule → cortical collecting ducts → Outer medullary collecting duct → Inner medullary collecting duct → Duct of bellini → ureter → bladder
What are the 2 types of nephron?
1- Cortical (superficial) nephrons supplies blood to the peritubular capillaries in the renal cortex
2- Juxtamedullary nephrons supplies blood to the Vascular Bundles and Vasa Recta in the renal medulla
- Renal cortex – 90% of blood flow (facilitates rapid reabsorption back into blood)
- Renal Medulla – 10% of blood flow (allows solutes to accumulate in medulla)
What separates the outer and inner medulla?
- The junction between the thick ascending limb and the thin ascending limb.
Histological slide demonstrating the reality of what Nephron looks like.
What will reabsorption from any one segment of the nephron do?
- It will alter the osmotic gradient for all other nephron segments
Reabsorbtion:
1- What are the 2 different pathways of reabsorption? What is reabsorption usually dependent on?
2- What is paracellular reabsorption dependent on? Where is only paracellular reabsorption possible?
3- What is transcellular reabsorption dependent on?
4- What does transcellular reabsorption utilise?
1- Paracellular + Transcellular > concentration, osmotic or electrical gradients between the tubular and the interstitial fluids.
2- Depends on the tightness of the junction between the cells > Proximal convoluted tubule as its the only part of the kidney which has these leaky junctions.
3- Requires both the luminal and basolateral membrane to be permeable to water or the solute of interest
4- Primary or secondary active transport can power transcellular transport against a concentration gradient
What is the role of reabsorption in Proximal convoluted tubule?
- 66% of all ions and water are also absorbed by a process called isosmotic fluid reabsorption.
(Almost 100% removal of HCO3- , amino acids and glucose - preventing lost of important nutrients, as well as keeping plasma pH constant)
> This significantly reduces the volume of fluid flowing through the tubules and slows its flow – allowing more time for exchange in remaining segments… increases time for reabsorption by diffusion/osmosis
Fluid entering the loop of Henle is isosmotic with plasma
Describe the process of Isosmotic reabsorption in PCT.
- What transporters are involved?
- Sodium glucose transport and sodium amino acid transport, helps us start to move sodium transcellularly through the cell in the proximal tubule.
- Glucose and Na+ are then transported through other transporters to get into the other side and be reabsorbed.
- Na+ reabsorption drives the creation of electrochemical gradient so the sodium uptake creates a positive electrochemical gradient across the lumen and the interstitium.
- This will then allow chloride reabsorption paracellularly as we’ve got a leaky junction in this particular region of the nephron so it moves down the electrochemical gradient.
- As it does this we absorb sodium chloride which creates an osmotic gradient to draw water also paracellularly through the cells- equal amounts so osmotic balance across the membrane stays the same hence why this process is called isosmotic reabsorption.
How do we move the filtrate from the interstitum into the blood stream?
How does the filtrate moves from the interstitium to the blood stream?
- Needs to move through the peritubular capillary bed.
- Low blood pressure and high colloid osmotic pressure favours a Net reabsorption of interstitial fluid into Peritubular capillaries ( look at image)
The Kidney responds to endocrine signals to regulate the reabsorption of the remaining ions and waters from the nephron.
- What plasma components do the following chemical messengers work on.. What is their effect on reabsorption?
In the absence of other signals urine is dilute, How?
- NaCl reabsorption is greater than water reabsorption, hence a highly diluted urine output
In order for the body to change its osmolarity, what must exist?
- A negative feedback loops with receptors/ sensors to identify an osmolarity change
Steps 2,3,4 of negative feedback loop:
1- What are osmoreceptors? Where are they found?
2- How do osmoreceptors work?
3- Where are neuronal signals sent to? What do they cause?
1- CNS neurons that change their neural firing rate/ action potential based upon the plasma osmolarity ( Found: OVLT/SFO)
2- Upon changes in the plasma osmolarity these neurons will change volume
> Stretch-inhibited ion channels open when the cell shrinks (plasma is hypertonic) - depolarising the cell and increasing the frequency of action potential firing in these sensor neurons.
3- Hypothalamus >
Increased thirst ↑ Drinking
Increased ADH secretion from posterior
pituitary Excrete less water in urine
What is the alternative name for ADH?
Increased ADH secretion from posterior pituitary =
- Vasopressin
= Excrete less water in urine.
What are the 2 things water reabsorption require?
1- Tubules to be permeable to water:
2- Osmotic gradient to drive water movement
Name the process where the loop of henle increases NaCl concentration of the interstitial/peritubular fluid? Explain how this results in concentrated urine.
- Countercurrent multiplication
What does Countercurrent multiplication do?
1- Tubular fluid from PCT to loop of Henly is….
2- Thin decending limb is ……….. due to the expression of aquaporin…
3- Interstitial fluid is …. to plasma
4- Where is the thick ascending limb (TAL) found in the kidney? What does the TAL actively pump and what is its maximum gradient through ATPase transport??
Increase the maximum osmolarity of the medullary interstitial fluids.
1- Isosmotic to plasma
2- Permeable to water …. 1
3- Isosmotic
4- Outer medulla > NaCl But only to a maximum gradient of 200 mOsm/L
How does counter current multiplication work to ensure more NaCl be reabsorbed after multiple fluid rotations? (5 key steps)
Anti diuretic hormone:
Without ADH we get dilute urine, explain how.
What does ADH do?
> Released by posterior pituitary, ADH makes all of the collecting duct permeable to water
1- ADH attaches to basal membrane of collecting duct on ADH/V2 receptor
2- G-protein activation > Activates adenyl cyclase > ATP into cAMP > Protein kinase A activation > Phosphorylation of aquaporin 2 within internal vesicles found within collecting ducts > Exocytosis of vesicles leading to insertion of aquaporin 2 into the tubular luminal membrane, therefore making it permeable to water.
> Water can now be reabsorbed down its osmotic gradient into the concentrated medullary interstitial fluid that was created by the loop of Henle.
Helps blood osmolarity to be lowered back toward its set value.
With ADH do we get concentrated urine or dilute urine? Explain your answer.
The problem with Urea:
1- What is the problem with Urea when water is reabsorbed by the release of ADH?
2- How is this problem dealt with?
Q1
- Urea concentration increases (same amount of urea dissolved in a smaller volume of water)
> Almost no urea is reabsorbed into the interstitial fluids.
» Thus water reabsorption creates a large urea concentration gradient across the collecting ducts
- This concentration gradient creates an opposing osmotic pressure gradient to that created by the NaCl from the loop of Henle, limiting water reabsorption from the collecting ducts
[Urea]TF > [Urea]IF
[NaCl]TF < [NaCl]IF
Q2
- ADH makes the inner medullary collecting duct permeable to urea, which allows urea to equilibrate with the urea in the interstitial fluid so that it cannot exert an osmotic pressure across the collecting duct
- NaCl continues to drive water absorption. And hence concentrates the urine
Equilbriation of Urea in the interstitial fluid and tubular fluid solves 1 problem however we need to excrete urea! By absorbing Urea we increase this toxic nitrogenous waste in blood….
- How do we prevent significant reabsorption of Urea back into the bloodstream? Describe the process.
-
Urea recycling
> build up a high [urea] in the tubular fluid – helping to maximise urea loss in the urine
> Builds up high [urea] in the medullary interstitial fluids
How does Urea enhance Counter current multiplication?
- Increase in the [urea] of the interstitial fluids also helps enhance the reabsorption of NaCl from the loop of Henle - which will allow greater water reasorption from the collecting ducts
→ Increase the maxmimum concentration of the urine to 1200 mOsm/L
Describe the process of how Urea enhances counter current multiplication.
7 steps
