Renal Blood flow and Glomerular Filtration Flashcards
What are the main functions of the kidney?
- Control volume and composition of body fluids
- Get rid of waste material from body
- Acid-Base balance
- As an endocrine organ – Renin, Erythropoietin, Vit. D
What are the membranes that the molecules have to pass to get into the Bowman’s capsule?
- Fenestrated Capillaries
- Basement membrane
- Filtration slits - formed of Podocytes, which coat outer surface of capillaries
*All these membrane are sieve-like, and they get finer as they reach the capsule.
How is the glomerular filtrate formed?
By Ultrafiltration - driven by the ↓BP across the glomerular membrane
• For small solutes: Filtrate concentration = Plasma concentration
• For plasma proteins: Filtrate concentration = 0 - presence in urine shows dysfunction in filtration
What is the role of Starling’s Principle in glomerular filtration?
Hydrostatic Pressure»_space; Plasma osmotic pressure + Pressure in Bowman’s space together = Net movement OUT of blood
Filtration Fraction = GFR/RPF (around 20%)
Eventhough BP drops along glomerulus, the net filtration force always stays > net absorptive force - GFR stays high
What is GFR?
What are the intrinsic and external controls of GFR?
- the amount of filtrate that’s removed from the blood each minute.
- Intrinsic: Autoregulation - keeps GFR relatively constant e.g. during ↑arterial BP
Extrinsic: Neurohormonal control
Explain the 2 mechanisms in GFR Autoregulation
- Bayliss Myogenic (BM) Response: direct vasoconstriction of AFFERENT arteriole in response to ↑perfusion pressure - ↑Perfusion = ↑Distention = BM Response activation
- Tubuloglomerular Feedback (TGF): flow-dependant signal detected in the Macula Densa, which affects vascular tone of afferent arteriole - ↑GFR = ↑ NaCl delivery to Macula Densa = ↑Release of Paracine and vasoconstrictive agents = ↑vascular tone
What is the mechanism in GFR Neurohormonal control?
- Renal sympathetic vasoconstrictor nerves can reset autoregulation at a lower level = ↓GFR
- Occurs in Standing up (Orthostasis), Haemorrhage/shock, Heavy exercise to ↑blood volume.
*Actions are aided by circulating vasoconstrictor hormones e.g. Adr, Ang, ADH
What are the 2 main clinical disorders of GFR?
- Nephrotic syndrome - Glomerulus is too leaky (filtration slits damaged by Nephrin deficiency) - leads to Proteinuria, Oedema
- Chronic Glomerulonephritis - GFR too low - due to non-functioning Glomerulus fibrosis - GFR < 30 = Chronic Renal Failure
What is the importance of GFR in monitoring renal functioning?
What the different substance types that can be used to measure GFR?
- GFR removes most of the waste material quickly, and is determined by the pressures and permeability of the glomerular membranes - these can be changed, therefore GFR is a good clinical indicator of renal/nephron function.
- Substance A e.g. creatinine: only filtration occurs - excretion rate = filtration rate
Substance B e.g. ions: filtration, partial reabsorption - excretion rate < filtration rate
Substance C e.g. glucose/AA: filtered, complete reabsorption - should be none in urine
Substance D e.g. organic acids: filtered, no reabsorption, some secretion - excretion rate > filtration rate
Explain the Inulin Method to measure GFR
What is the formula used?
Inulin is an unreactive polysaccharide that is filtered without any reabsorption, secretion, or metabolism (Sub. A) - filtration rate = rate of urine bladder entry
GFR = (Urine [Inulin] x Urine flow rate) / Plasma [Inulin]
*the rates in ml/min, the conc. in mg/ml
What is Renal clearance?
What is the formula used?
Renal clearance of a substance is the VOLUME of plasma that is completely cleared of that substance by the kidney per unit of time (ml/min)
Clearance rate = (Urine conc. x Urine flow rate) / Plasma conc.
*all in seconds
Why is the Creatinine method preffered clinically for measuring GFR, instead of Inulin?
How is Creatinine made in the body?
- Inulin isn’t made in the body so requires prolonged infusion and many blood samples. Creatinine is much better as it’s made in the body, is unreactive, released from skeletal muscle, and requires no infusion.
However, after filtration, there’s no reabsorption, but there’s some secretion, therefore the amount excreted > amount filtered.
- In skeletal muscle:
Creatine + Phosphocreatine → Creatinine
What is eGFR and how is it calculated?
How is GFR/eGR used to stage CKD?
- Estimated GFR and it takes into account age and gender etc. It’s calculated using the MDRD equation (x0.742 - female, x1.21 - black). Is very easy as it only requires one blood test.
Will be very inaccurate in extreme body types e.g. malnourishment, pregnant.
- Chronic Kidney Disease (CKD) assessment is based on GFR - has 5 stages. Stage 1 is normal and GFR is >90, and GFR decreases as stages go up.
What does the clearance rates of substances compared to inulin suggest about how it’s handled by the kidney?
- Clearance > Inulin: freely filtered with some secretion
- Clearance = Inulin: handled the same way as Inulin
- Clearance < Inulin: either poor filtration or there is reabsorption
Explain the Renal threshold and Transport maximum (Tm) using the graph of filtration/reabsorption/excretion against plasma [glucose]
LOOK AT GRAPH IN NOTES!
- Glucose freely filtered and is completely reabsorbed in the PCT - via SGLT-2
- The Tm of SGLT-2 is about 20mM - Glucose starts being excreted in the urine when plasma [glucose] exceeds the Renal Threshold
*Normal urine will have no glucose due to no excretion (plasma [glucose] < renal threshold), but a diabetic’s urine will have glucose due to some excretion (plasma [glucose] > renal threshold)
