Glomerular Filtration and Assessment of Renal Function Flashcards by Rosie Ellis

What percentage of cardiac output do the kidneys receive?

20%

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What is the difference in composition between plasma and interstitial fluid?

Proteins in plasma but not in interstitial fluid

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What substances are usually excluded from filtrate?

Most plasma proteins

Blood cells

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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

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What factors determine glomerular filtration rate? (GFR)

GFR= Kf x NFP

Kf= glomerular capillary filtration coefficient
NFP= net filtration pressure

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What is the GFR?

Glomerular filtration rate: volume of filtrate formed by all the nephrons in both kidneys per unit time

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What is the glomerular capillary filtration coefficient? (Kf)

Determined by:

Surface area available for filtration
Hydraulic conductivity (permeability) of the filtration barrier

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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 = P_G - P_B - π_G + π_B

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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.

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What is the effect of afferent arteriolar constriction and/or efferent arteriolar dilation on glomerular hydrostatic pressure?

Reduced glomerular capillary pressure (P_GC) therefore reduced GFR

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What is the effect of afferent arteriolar dilation and/or efferent arteriolar constriction on glomerular hydrostatic pressure (P_G)?

Increased glomerular hydrostatic pressure (P_G) therefore raised GFR

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Which 2 factors can alter glomerular hydrostatic pressure (P_G) independently of arterial blood pressure?

Afferent arteriolar resistance

Efferent arteriolar resistance

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What are the factors affecting glomerular hydrostatic pressure?

Renal artery pressure

Afferent arteriolar resistance

Efferent arteriolar resistance

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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)

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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

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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)
1. Increased renin from granular cells→Increases angiotensin II→Increased efferent arteriole resistance (RAAS system)
2. 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)