RENAL - Glomerular Filtration and Renal Blood Flow Flashcards
Label the diagram of the nephron on SLIDE 8.
COMPLETE
What is the usual GFR per day?
180 litres per day
How are the glomerular capillaries specialised for filtration?
- Endothelial cells have fenestrations - free movement of molecules out of blood
- Underneath is basement membrane - collagenous barrier to large molecules
- Podocytes - final layers - specialised cells with foot like processes encapsulating capillary.
- Small gaps between processes prevent escape of larger molecules
Describe the charges of the layers of the glomerular capillaries and what they can and cannot filter.
- NEGATIVELY CHARGED - repel substances in blood - small enough to pass through filter but are negatively charged themselves
- RBCs not filtered - smaller substances dissolved in plasma (such as water, salts and glucose) are freely filtered
Describe the pressures at work in the glomerulus that facilitate blood filtration.
- HYDROSTATIC - pressure exerted by blood on walls of capillaries.
- COUNTERING PRESSURE from filtered fluid within Bowman’s capsule
- ONCOTIC - osmotic pressure exerted by plasma proteins that drive fluid back - high pressures in capillaries drive fluid back across glomerulus into blood
- ONCOTIC PRESSURE OF CAPSULE negligible - because so few proteins dissolved in filtrate
How can net filtration pressure be calculated?
Net Filtration Pressure = HPGC – HPCS - πGC
- Normally 10 mmHg of driving pressure from capillaries into nephron
(a) What does net filtration pressure only take into account?
(b) What is the effect of the capillaries being fenestrated?
(a) Driving pressure of individual nephrons
(b) Surface area larger than normal capillaries
What is GFR and what is a formula for it?
- Volume of fluid filtered at all glomeruli in a given timeframe
- GFR = Vascular permeability coefficient x net filtration pressure
- Permeability coefficient - accounts for permeability and surface area of capillaries
(a) What makes arterioles special?
(b) What happens when afferent arteriole is constricted?
(a) Constrict due to smooth muscle
(b) Reduced volume of blood flowing into glomerulus - reduced hydrostatic pressure within glomerulus - reduced GFR
What happens when efferent arteriole is constricted?
- Reduced volume of blood leaving glomerulus - blood backs up in glomerulus
- Raised hydrostatic pressure
- GFR increases
Describe changes to hydrostatic pressure in the Bowman’s capsule.
- Don’t normally occur
- In pathological states - such as urinary tract obstructions - raised pressure.
- GFR decreases
Describe renal plasma clearance and how is rate of excretion calculated.
- Rate of removal and excretion of substances from plasma
- RATE OF EXCRETION = (FILTRATION RATE + SECRETION RATE) - REABSORPTION RATE
- Account for secretion - because some substances secreted into nephron by peri-tubular vessels
What is the formula for rate of clearance of a substance?
(Concentration of substance in urine multiplied by volume of urine) divided by concentration of substance in plasma
What happens if a substance is freely filtered but not secreted or reabsorbed?
Clearance = GFR
Describe inulin.
- Dietary fibre
- Freely filtered at glomerulus
- Not reabsorbed or secreted
- Not toxic
- Clearance = GFR
- Infusions used to clinically determine GFR (not entirely convenient - infusions have to be constant over given timeframe to maintain constant plasma level)
What happens if a substance is freely filtered but reabsorbed?
Clearance < GFR
- Example is glucose - clearance from plasma = 0ml/min
What happens if a substance is not reabsorbed but is freely filtered and secreted?
Clearance > GFR
Describe PAH (para-amino hippuric acid)
- Freely filtered at glomerulus
- Secreted into tubule and not reabsorbed
- Completely cleared from plasma
- Rate of clearance = renal plasma flow
Give examples of clearance values for inulin, creatinine and PAH.
- 125 ml/min for both inulin and creatinine.
- CREATININE - product of muscle breakdown. Produced at constant rate - freely filtered at glomerulus but slightly secreted. GFR overestimated by about 10% - can be used clinically
- PAH - 600 ml/min
What is the formula for eGFR and how can it be determined?
eGFR = 175 × [creatinine× 0.011312]-1.154× [age]-0.203× [1.212if afro Caribbean race] × [0.742if female]
- Determined from serum creatinine
- An eGFR >90ml/min/1.73m2 is considered normal, with kidney disease categorised by decreasing levels of eGFR
Describe autoregulation in the kidneys
- Volume of blood delivered to kidneys exceeds metabolic demand
- Maintains constant GFR between systemic arterial BP of 70-180 mmHg
- If blood pressure were to increase by 25% (from 100mmHg to 125mmHg), GFR would increase similarly (from 180L/day to 225 L/day).
- If reabsorption stayed the same, then urine output would increase to around 46L/day.
- Given that plasma volume is around 3L, this would rapidly lead to hypovolaemia
(a) How much blood do the kidneys receive?
(b) What is the formula for renal blood flow?
(c) Describe total renal vascular resistance.
(a) 1litre per minute (20% of cardiac output)
(b) (RENAL ARTERY PRESSURE - RENAL VEIN PRESSURE) divided by total renal vascular resistance
(c) Determined by resistance in interlobar arteries, afferent/efferent arterioles. Kidneys - strong control over blood flow. Changes in arterial pressure don’t result in large changes to RBF
Describe tubuloglomerular feedback. PART 1
- Reduced blood pressure - reduced renal perfusion - decrease in GFR
- Decrease in flow through Loop of Henle - increase in amount of NaCl that can be reabsorbed (in contact with nephron for longer)
- Decreased sodium reaches distal tubule
- Reduced sodium detected by macula densa cells in JGA
Describe tubuloglomerular feedback. PART 2
- Macula densa cells send signal to afferent arteriole which dilates
- Signal sent to juxtaglomerular cells - RAAS activated - increased AngII concentration - constriction of efferent arteriole
- Increased hydrostatic pressure in glomerular capillaries - increase and normalisation of GFR
Describe myogenic control in intrinsic control of RBF.
- Pulse pressure exerted on walls of arteries
- Calcium enters smooth muscle cells - reflex contraction
- VASOCONSTRICTION - reduced blood flow, maintains GFR and protects glomerulus from hypertensive damage
- Prevents kidney damage during hypertension
Describe control of RBF. PART 1
- Decreased BP (via decrease in sodium delivery to distal tubule) activates baroreflex - stimulates renal sympathetic nerve activity
- Nerves stimulate juxtaglomerular cells - increase renin releases and AngII circulation
- Decreased BP (via decrease in sodium delivery to distal tubule) activates baroreflex - stimulates renal sympathetic nerve activity
Describe control of RBF. PART 2
- AngII constricts renal vessels e.g afferent arteriole - can be counteracted by locally produced vasodilatory factors e.g NO
- Causes preferential vasoconstriction of efferent arteriole - increased GFR through increase in glomerular hydrostatic pressure
- AngII constricts renal artery - decrease in RBF.
- Decreased RBF and increased hydrostatic pressure - normal GFR maintained
Describe the role of renal sympathetic nerves.
- Innervates almost all blood vessels in kidneys
- SEVERE DROP IN BLOOD VOLUME/PRESSURE - activation of nerves. Constriction of blood vessels and decreased GFR
- Mild/moderate sympathetic stimulation - little effect on RBF - activates RAAS to increase sodium and water reabsorption
- Constriction of blood vessels via the renal sympathetic nerves appears to be most important during severe acute disturbances, such as haemorrhage or brain ischaemia
How can vascular permeability coefficient be measured?
Rearranging the GFR formula
Normally around 12.5 ml/min/mmHg
Describe the juxtaglomerular apparatus.
- Consists of the macula densa, which are a group of specialised cells on the wall of the distal tubule, and the juxtaglomerular cells, that line the wall of the afferent and efferent arterioles
