Physiology: Glomerular Filtration & Renal Blood Flow Flashcards
What is glomerular filtration? Briefly describe it
GF is the first step in the formation of tubular fluid
A portion of the plasma flowing through the glomerulus (~20%) is filtered across into the lumen of the Bowman’s capsule to become tubular fluid
What are the 3 barriers to filtration?
- Glomerular capillary endothelium
- Basement membrane (between the endothelium of the glomerular capillaries and the podocytes of the inner layer of Bowman’s capsule)
- Slit processes of the podocytes (of the inner layer of the Bowman’s capsule)
What particular component of plasma are the 3 filtration barriers barriers to?
- Glomerular capillary endothelium: barrier to rbc’s
- Basement membrane: barrier to plasma proteins
- Slit processes of the podocytes: barrier to plasma proteins
So fluid filtered from the glomerulus into the Bowman’s capsule must pass through the 3 layers that make up the glomerular membrane.
Describe how the capillary endothelium cells act as a barrier to rbc’s
Pores between the single endothelial cell layer are not large enough to permit the passage of rbc’s through to the Bowman’s capsule
How does the permeability of glomerular capillary endothelium compare to that of a normal capillary?
Even though they are not large enough for rbc’s to pass through, the pores between the endothelial cells are larger than normal, making glomerular endothelium ~100x more permeable than normal endothelium
So fluid filtered from the glomerulus into the Bowman’s capsule must pass through the 3 layers that make up the glomerular membrane.
Describe how the basement membrane (aka basal lamina) acts as a barrier to plasma proteins
It is an acellular layer made up of collagen and glycoproteins
These give it a net -ve charge which acts as a barrier to large plasma proteins ~ large plasma proteins cannot enter the Bowman’s capsule
So fluid filtered from the glomerulus into the Bowman’s capsule must pass through the 3 layers that make up the glomerular membrane.
Describe how the podocytes act as a barrier to plasma proteins
Filtration slits between podocytes allow only small substances to pass into the Bowman’s capsule to form the initial tubular fluid
Glomerular filtration is a passive process. What are the 4 forces that drive filtration?
Glomerular capillary blood pressure (hydrostatic)
Capillary oncotic pressure
Bowman’s capsule hydrostatic pressure
Bowman’s capsule oncotic pressure
Does glomerular capillary blood pressure favour or oppose filtration?
Give its approximate value
Glomerular capillary blood pressure is the most important hydrostatic pressure
It favours filtration
Approximate value: 55mmHg
What is glomerular capillary oncotic pressure?
A plasma protein concentration gradient that exits because plasma proteins are retained in the capillaries and excluded from the Bowman’s capsule
Does glomerular capillary oncotic pressure favour or oppose filtration?
Give its approximate value
Opposes filtration
(because the high protein content in the capillaries wants to pull the filtrate back in)
Approximate value: 30mmHg
Does Bowman’s capsule hydrostatic pressure favour or oppose filtration?
Give its approximate value
Opposes filtration
(because tubular fluid formed by the filtration process opposes further filtration)
Approximate value: 15mmHg
Does Bowman’s capsule oncotic pressure favour or oppose filtration?
Give its approximate value
Favours filtration
Approximate value: 0mmHg
as no plasma proteins enter the Bowman’s capsule
How is net filtration pressure calculated?
Forces favouring filtration - forces opposing filtration
Calculate net filtration pressure using the approximate values for the 4 forces that drive glomerular filtration
Net filtration pressure
= forces favouring filtration - forces opposing filtration
= (glomerular capillary BP + BC oncotic pressure) - (glomerular capillary oncotic pressure + BC hydrostatic pressure)
= (55 + 0) - (30 + 15)
= 10 mmHg
What is meant by the term ‘Starling Forces’?
The balance of hydrostatic and osmotic pressures
What is glomerular filtration rate (GFR)?
The rate at which protein-free plasma is filtered from the glomeruli into the Bowman’s capsule per unit time
How is GFR calculated from net filtration pressure?
GFR = Kf x net filtration pressure
What is Kf?
Filtration coefficient
This means how permeable the glomerular membrane is
Name 2 factors that can alter the filtration coefficient (Kf). What happens to GFR if it is altered?
Kf can be altered by disease or drugs
Reduced Kf will reduce GFR, increased Kf will increase GFR
What is the normal value for GFR?
~125 ml/min
What force is the major determinant of GFR?
Glomerular capillary blood pressure (hydrostatic)
Name a pathology which increases the Bowman’s capsule hydrostatic pressure
How does this affect GFR?
Kidney stone causes obstruction and so fluid build up in the nephron -> decreased GFR
(as this force opposes GFR)
Name a pathology which increases the capillary oncotic pressure
How does this affect GFR?
Diarrhoea causes dehydration which concentrates the plasma proteins in the capillaries -> decreased GFR
(as this force opposes filtration)
Name a pathology which decreases the glomerular capillary oncotic pressure
How does this affect GFR?
Severe burns cause plasma proteins to be lost from the site of injury -> increased GFR
(as this force opposes filtration)
What extrinsic mechanism functions to regulate GFR and renal blood flow?
Sympathetic control (e.g., via the Baroreceptor reflex)
Describe the effect of increased arterial blood pressure on GFR and renal blood flow
- Increased arterial blood pressure
- Causes vasodilation of the afferent arteriole
- This increases blood flow into the glomerulus
- This increases glomerular capillary blood pressure
- So net filtration pressure increases
- Increasing GFR
Describe the effect of decreased arterial blood pressure on GFR and renal blood flow
- Decreased arterial blood pressure
- Causes vasoconstriction of the afferent arteriole
- This decreases blood flow into the glomerulus
- This decreased glomerular capillary blood pressure
- So net filtration pressure decreases
- Decreasing GFR
Describe how the Baroreceptor reflex regulates GFR when arterial blood pressure decreases
- Decrease in arterial blood pressure e.g., haemorrhage
- Detected by aortic body and carotid sinus baroreceptors
- Resultant increase in sympathetic activity
- Generalised arteriolar vasoconstriction
- Constriction of afferent arterioles
- Reduced renal blood flow and glomerular capillary blood pressure
- Reduced GFR
- Decreased urine output
How does decreased urine output help with drop in blood volume e.g., due to haemorrhage?
It helps compensate for blood volume loss by preventing further loss of ECF volume
Name 2 intrinsic mechanisms that autoregulate GFR and renal blood flow
The myogenic mechanism
The tubuloglomerular feedback mechanism
What is the role of intrinsic autoregulation of GFR?
To prevent short-term changes in systemic arterial pressure from affecting GFR and renal blood flow
e.g., preventing increased BP during exercise from increasing GFR to increase urine output and lower BP
Describe the intrinsic myogenic mechanism involved in GFR autoregulation
When vascular smooth muscle is stretched by increased arterial blood pressure, it contracts to constrict the arteriole and reduce blood flow to the glomerulus
Describe the intrinsic tubuloglomerular feedback mechanism involved in GFR autoregulation
- Macula densa cells in the juxtaglomerular apparatus sense the NaCl content of the tubular fluid
- Increased GFR increases tubular fluid flow which increases NaCl
- In response, macula densa cells release vasoactive chemicals which cause the smooth muscle in the afferent arteriole wall to vasoconstrict
- Vasoconstriction reduces blood flow to the glomerulus, decreasing GFR in a negative feedback loop
What is plasma clearance?
The volume of plasma completely cleared of a particular substance per minute
How is plasma clearance of a substance calculated?
Clearance
= rate of excretion / plasma conc.
= (urine conc. x rate of urine production) / plasma conc.
(ml/min)
Name a substance for which clearance = GFR
Inulin (a polysaccharide found in plants (onions and garlic)
Why does inulin clearance = GFR?
Inulin is freely filtered at the glomerulus i.e., it can bypass all of the barriers to filtration
It is then neither reabsorbed nor secreted within the tubules
Suggest how to calculate GFR using inulin clearance
Inulin clearance
= rate of excretion / plasma conc.
= (urine conc. x rate of urine excretion) / plasma conc.
= GFR
Why is creatinine clearance used to determine GFR instead of inulin?
Because inulin is an exogenous substance so must be administered into the patient via IV infusion
This is impractical
Why does creatinine clearance not give an exact measurement of GFR?
A small amount (~5-10%) is undergoes renal secretion
List the properties a substance should have to make it a suitable indicator for GFR measurement
- Endogenous
- Easy to measure
- Appears at a constant rate
- Freely filtered at the glomerulus
- Not reabsorbed from the renal tubule
- Not secreted into the renal tubule
- Doesn’t undergo extra-renal elimination
What is the clearance for substances which are…
- Filtered, completely reabsorbed + not secreted
- Not filtered, not reabsorbed + not secreted
…?
Clearance = 0 ml/min
as all of the substance is reabsorbed back into the bloodstream and not excreted
What is the clearance for substances which are filtered, partly reabsorbed + not secreted?
Clearance < GFR (i.e., <125 ml/min)
as only a portion of the filtrate is excreted
What is the clearance for substances which are filtered, not reabsorbed + are secreted?
Clearance > GFR (i.e., >125 ml/min)
as all of the filtrate is cleared as it is not reabsorbed, then the additional secreted substance is also cleared
Suggest clearance values for…
- Inulin
- H+
- Urea
- Glucose
- Creatinine
Inulin: 125 ml/min (filtered, not reabsorbed, not secreted)
H+: >125 ml/min (filtered, not reabsorbed, secreted)
Urea: <125 ml/min (filtered, partly reabsorbed, not secreted)
Glucose: 0 ml/min (filtered, totally reabsorbed, not secreted)
Creatinine: ~125 ml/ml (filtered, not reabsorbed, slightly secreted)
Define…
- Renal plasma flow (RPF)
- Renal blood flow (RBF)
- Renal plasma flow (RPF): the volume of plasma (55% of the blood composition) delivered to the kidneys per unit time
- Renal blood flow (RBF): the volume of blood delivered to the kidneys per unit time
List the properties a substance should have to make it a suitable indicator for renal plasma flow measurement
- Non-toxic
- Inert (not metabolised)
- Easy to measure
- Filtered by the glomerulus
- Completely secreted by the tubules
What is the best substance for measuring renal plasma flow and why?
Para-amino hippuric acid (PAH - an exogenous organic anion)
It is freely filtered at the glomerulus, not reabsorbed, and the plasma that escapes filtration is completely secreted from the tubule
This means that all of the PAH is excreted/cleared
What is the approximate value of renal plasma flow (RPF) in a health adult?
PAH clearance = RPF = ~650 ml/min
What is filtration fraction?
The fraction of plasma that flows through the glomeruli which undergoes glomerular filtration
What is the filtration fraction in a normal healthy adult?
~20%
The remaining 80% moves onto the peritubular capillaries/vasa recta
How is filtration fraction calculated?
FF = GFR / RPF = 125/650 = 0.19 = ~20%
How is renal blood flow (RBF) calculated from renal plasma flow (RPF)?
RBF
= RPF x (1 / (1-Hct)
What is Hct?
A measurement of blood haematocrit
or packed cell volume - PCV
What is the average renal blood flow in a healthy adult?
RBF
= RPF x (1/ 1-Hct)
= 650 x 1.85
= ~1200 ml/min
For a subject at rest, the kidneys receive ~X% of cardiac output
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