Physiology 2 Flashcards
Are WBC, RBCs and platelets filtered?
No
How come when in clinic one does a dipstick looking for WBC or RBCs it sometimes comes back positive?
It should not be there
Is albumin filtered?
In very small amounts
What happens to albumin filtration in a disease state?
It goes up
Why does albumin go up in blood filtrate in a disease state?
The nephrons lose their negative charge, thus they do not repel albumin and it enters the filtrate
Are small peptides filtered?
Yes in small amounts - larger in disease states
Are small ions filtered?
Yes, this may decrease in disease states
Are organic solutes (free) filtered?
Yes, this may decrease in disease states
Are organic solutes (protein bound) filtered?
No, can be variable in disease states
Are drugs (free) filtered?
Yes, this may decrease in disease states
Are drugs (protein bound) filtered?
No, can be variable in disease states
What actually forms the sites of filtration?
It is the podocytes and their foot processes which surround the endothelial and form the 2nm negatively charged slits
When are the negative charges of the podocytes lost?
Diabetic nephropathy (and a number of other nephropathies)
What is a detected if glomeruli are diseased?
Albumin (called microalbuminurea)
Where are mesangial cells located?
Mesangial cells are specialized cells around blood vessels in the kidneys
What is the role of mesangial cells?
They are specialized smooth muscle cells that function to regulate blood flow through the capillarie
What hormone do mesangial cells respond to?
Angiotensin II (they have ANGII receptors)
What is the renal blood flow per minute?
1L/Min (very large)
What is the plasma blood flow to the kidney per minute?
600ml/Min (hematocrit of 400ml/min)
What is a standard filtration fraction?
20%
What determines the filtration fraction?
The permeability is fixed by the structure of the podocytes.
The length of the glomerular network
(These do not vary a great deal)
The pressures (These change substantially)
What are the pressures which affect GFR?
- Hydrostatic pressure in the glomerular
- Hydrostatic pressure in Bowman’s capsule
- Oncotic pressure in the glomerular capillary
- Oncotic pressure in Bowman’s capsule
What is the Hydrostatic pressure in the glomerular capillary?
50mmHg
There is a pressure drop of about 40 down the afferent arteriole
What is the Hydrostatic pressure in Bowman’s capsule?
10mmHg
What is the Oncotic pressure in the glomerular capillary?
25 (arterial end) → 40 (distal end) mmHg
This is due to the fact that the plasma proteins cannot readily diffuse across into Bowman’s space.
What is the Oncotic pressure in Bowman’s capsule?
≈0 mmHg
What is the pressure forcing fluid out at the beginning of the glomerulus?
50mmHg (hydrostatic from blood) - 10mmHg (pushing from capsule back towards the blood) = 40mmHg
Oncotic pressure at the start = 25mmHg
40-25 = 15mmHg
What is the pressure forcing fluid out at the end of the glomerulus?
50mmHg (hydrostatic from blood) - 10mmHg (pushing from capsule back towards the blood) = 40mmHg
Oncotic pressure at the end = 40mmHg
40-40 ≈ 0 mmHg
It is thought that this occur well before the end of the capillary leading to a zone in which no transfer is taking place
What is autoregulation?
It is the process by which the kidney can maintain its normal function (i.e. filtration rate) against a range of systemic blood pressures
What is the range in which autoregulation is effective?
Maintained at a MAP of between 80-180mmHg
Why are glomerular capillaries vulnerable to damage?
Blood is flowing through at a high pressure (50mmHg - as opposed to 10mmHg in normal capillaries)
Why is the pressure so high in the glomerular capillaries?
There is another resistance vessel after the capillaries (the efferent arterioles) which together with the afferent arteriole equally reduces the pressure
What is the peritubualr capillary pressure
5-10mmHg
What happens to glomerular pressure if the afferent arteriole is constricted?
It will decrease
What happens to GFR when the afferent arteriole constricts?
It will decrease
What happens to glomerular pressure if the efferent arteriole is constricted?
It will increase
What happens to GFR when the efferent arteriole constricts?
It will increase
What happens to GFR when MAP increases from 90-110mmHg?
GFR doesn’t change
How does autoregulation work?
It maintains a constant hydrostatic pressure within the glomerular capillary DESPITE changes in MAP
How is autoregulation maintained?
The afferent arteriole is dilated or constricted in order to maintain the pressure in the glomerulus
What are the autoregulation mechanisms?
Myogenic response of the renal arteries
Tubuloglomerular feedback (TGF)
What is the myogenic response?
Inherent property of the afferent artery whereby it opposes distension.
If it starts to be distended it reacts by trying to contract.
So in the case of high blood pressure which would dilate it it opposes this by constricting
What is tubuloglomerular feedback?
The cells of the macula densa are intimately related to the extra-glomerular mesangial cells which in turn abut against granular cells which surround the afferent arteriole (which are not normally found in an afferent arteriole).
In this way it is possible to inform the glomerulus of how much tubular flow is going on.
If there is too much tubular flow the glomerular filters less
How does the macula densa communicate tubular flow to the afferent arteriole?
The macula densa cells respond to increased chloride concentration (which is the result of high nephron flow rates).
Increases in chloride concentrations cause calcium channels to open and allow calcium to enter the macula densa cells.
A paracrine signal is then sent through the extra-glomerular mesangial cells causing them to release paracrine factors (the most important of which is adenosine)
Adenosine acts on the granular cells which have adenosone type 1 receptors causing them to constrict causing a general vasoconstriction
This will normalise GFR
What is another function of granular cells of the afferent arterioles?
They make and store renin
Why is it important to have such a high GFR?
It is the only way to get rid of toxic substances which are present at low concentrations
How do we calculate the excretion of a substance?
Urine concentration of W x Urine volume
= UV
How do we determine the renal clearance?
Rate of urinary excretion of W, relative to its plasma concentration
= excretion of substance W/plasma concentration of W
= UV/P
How is the clearance of substance X defined?
It is the volume of plasma cleared of X per time
What gives us the best indication of GFR?
A substance which is:
Freely filtered
Not reabsorbed
Not secreted
How is GFR measured?
Set up an infusion of Inulin to establish a steady plasma concentration
Collect urine and measure the amount of inulin
Concentration is exactly equal to the amount which is filtered because there is no reabsorbtion and no secretion
Whilst this is in theory a good measure in practise it is not often done rather the amount of creatinine is measured
What is used generally to measure GFR?
Creatinine
Not perfect but a good approximation
Why is creatinine used to measure GFR?
It is broken down fairly constantly from muscle tissue by the breakdown of creatine phosphate
The creatinine concentration is fairly constant during the day
Creatinine is not reabsobed
However creatinine is secreted into the lumen (though not large)
Is glucose reabsorbed?
Unless the concentration is very high all of the glucose is reabsorbed
Why would glucose be in the urine?
Concentration could be so high that the reabsorption mechanisms are being overloaded
What is the rate of penicillin clearance?
It is 150ml/min = higher than the GFR
It is both freely filtered and also secreted
What are the transporters that move pencillin into the lumen?
There are non specific transporters that move acidic organic substances into the lumen
