Glomerular Filtration and Assessment of Renal Function Flashcards
What percentage of cardiac output do the kidneys receive?
20%
What is the difference in composition between plasma and interstitial fluid?
Proteins in plasma but not in interstitial fluid
What substances are usually excluded from filtrate?
Most plasma proteins
Blood cells
What is the role of the fenestrations in the endothelium of the filtration barrier?
What is the role of the negatively charged basement membrane?
Filters out large molecules
Negative charge repels smaller particles (e.g. albumin) which may otherwise fit through the barrier
What factors determine glomerular filtration rate? (GFR)
GFR= Kf x NFP
- Kf= glomerular capillary filtration coefficient
- NFP= net filtration pressure
What is the GFR?
Glomerular filtration rate: volume of filtrate formed by all the nephrons in both kidneys per unit time
What is the glomerular capillary filtration coefficient? (Kf)
Determined by:
- Surface area available for filtration
- Hydraulic conductivity (permeability) of the filtration barrier
What is the NFP?
What is it determined by?
The net pressure acting against the filtration barrier. Sum of:
- Glomerular hydrostatic pressure
- Glomerular colloid oncotic pressure
- Bowman’s capsule hydrostatic pressure
NFP = PG - PB - πG + πB
What is the glomerular colloid osmotic pressure?
Why is this same pressure not present in the Bowman’s capsule?
Osmotic pressure exerted by the proteins in the plasma pulling water back into the glomerular capillaries and opposing the glomerular hydrostatic pressure.
Not present in the Bowman’s capsule as proteins are not present in the filtrate.
What is the effect of afferent arteriolar constriction and/or efferent arteriolar dilation on glomerular hydrostatic pressure?
Reduced glomerular capillary pressure (PGC) therefore reduced GFR
What is the effect of afferent arteriolar dilation and/or efferent arteriolar constriction on glomerular hydrostatic pressure (PG)?
Increased glomerular hydrostatic pressure (PG) therefore raised GFR
Which 2 factors can alter glomerular hydrostatic pressure (PG) independently of arterial blood pressure?
Afferent arteriolar resistance
Efferent arteriolar resistance
What are the factors affecting glomerular hydrostatic pressure?
Renal artery pressure
Afferent arteriolar resistance
Efferent arteriolar resistance
What substances raise glomerular hydrostatic pressure (and therefore GFR)?
What do they act on?
Vasoconstriction of efferent arterioles:
- Angiotensin II
Vasodilation of afferent arterioles:
- Prostaglandins
- Atrial natriuretic peptide
- Nitric oxide
- Kinins
- Dopamine (low dose)
What substances reduce glomerular hydrostatic pressure (therefore GFR)?
Constriction of afferent arterioles:
- Endothelin
- Noradrenaline (sympathetic nervous system)
- Adenosine
- Vasopressin
- Angiotensin II (high dose)
- PG blockade
Dilation of efferent arterioles:
- Angiotensin II blockade
Why is reabsorption favoured over filtration in the peritubular capillaries?
- Reduction in capillary hydrostatic pressure
- Increase in colloid osmotic pressure due to concentrating of plasma proteins in blood leaving the glomerulus.
What are the mechanisms of autoregulation of GFR?
- Myogenic response
- Tubuloglomerular feedback
What is the myogenic response?
Negative feedback loop
Smooth muscle in afferent arterioles respond to changes in vessel circumference by contracting or relaxing:
- Increase arterial BP
- Increased renal blood flow and GFR
- Increased stretch of afferent arteriole smooth muscle cells
- Ca2+ channels open
- Vasoconstriction of afferent arterioles
- Increases resistance to flow
- Prevents changes in renal blood flow to glomerulus therefore GFR.
How does tubuloglomerular feedback maintain renal blood flow and GFR if arterial pressure is raised?
- Increase in arterial BP
- Increased renal blood flow and GFR
- Increased [NaCl] delivered to macula densa
- Release of paracrine factors (e.g. adenosine)
- Constriction of AA smooth muscle
- Vasoconstriction of AA
- Increased resistance to flow
- Restores normal blood flow and GFR
How does tubuloglomerular feedback maintain renal blood flow and GFR if arterial blood pressure falls?
- Arterial BP falls
- Decreased glomerular hydrostatic pressure
- Decreased GFR
- Less [NaCl] delivered to macula densa (more proximal absorption)
- Increased renin from granular cells→Increases angiotensin II→Increased efferent arteriole resistance (RAAS system)
- Decreased adenosine→ decreased afferent arteriole resistance
What does proteinuria/haematuria/albuminuria indicate?
Damage to filtration barrier
Strong association between proteinuria and rate of disease progression in chronic kidney disease
What do eGFR/creatinine/urea indicate?
Functional status of the kidney
What other tests aside from eGFR can be used to indicate kidney function?
- Calcium/phosphate homeostasis
- U&Es / pH
- Urine volume/ fluid balance
- Haemoglobin
How is GFR measured?
Using renal clearance: the volume of plasma from which a substance is completely cleared by the kidneys per unit time.
How is renal clearance calculated?
Clearance (ml/min) = V (ml/min) x U (ml/min)
P (mg/ml)
V= volume of urine produced per minute
U= substance concentration in urine
P= Substance concentration in plasma
What is the ideal test of GFR?
Renal clearance of inulin = GFR
What non-routine test can be used to approximate GFR?
Creatinine
- Breakdown product of creatine, a skeletal muscle component.
- Completely filtered by the kidney and no absorption
- However small amount of secretion means it over-estimates GFR slightly.
Requires 24 hour urine collection: issues with time, compliance, reliability.
How can serum urea be used to approximate GFR?
What else should be considered when interpreting a serum urea result?
What should it be compared with when considering renal disease?
- Completely filtered by the kidney but partially reabsorbed.
- Levels rise in kidney disease as GFR falls
However, rise in serum urea can be caused by other factors:
- Dehydration/hypotension
- High protein diet
- GI bleed (digestion and absorption of blood products)
- Increased catabolism
- Drugs: corticosteroids, tetracyclines
Should be compared with serum creatinine: if both raised a fall in GFR is likely. If disproportionately higher than creatinine, consider the above.
How is GFR measured routinely?
- Serum creatinine
- Serum urea
- eGFR
How can serum creatinine be used to estimate GFR?
What are its limitations?
Completely filtered by kidneys but some secretion also; always slightly higher than true GFR.
Limitations:
- Levels of production varied between individuals
- Relates to muscle mass which varies with:
- Age
- Sex
- Malnutrition
- Amputations/ muscle wasting (less creatinine, can appear normal even if diseased kidneys
- Ethnicity
- Varies according to diet
- Not useful for early kidney disease (can lose 50% of kidney function and still have normal serum creatinine)
How is eGFR calculated?
CKD-EPI equation using serum creatinine, age, sex and ethnicity.
(recommended by NICE)