Q1 LONG ANSWER 10M ★ High-yield

Define glomerular filtration rate. Describe the filtration barrier, the forces governing filtration, and the factors affecting GFR. Add a note on autoregulation.

Physiology · 1st Professional — Pre-Clinical

The Nephron

Nephron = the structural and functional unit of the kidney.About 1–1.3 million per kidney.

Type	Proportion	Site of glomerulus	Loop of Henle	Function
Cortical	85%	Outer cortex	Short	Excretion and reabsorption
Juxtamedullary	15%	Near the corticomedullary junction	Long, reaching the papilla	Concentration of urine — provide the counter-current system

Definition of GFR

Glomerular filtration rate (GFR) = the volume of plasma filtered by all the glomeruli of both kidneys per minute.Normal = 125 mL/min = 180 L/day

Of 180 L filtered daily, only 1–1.5 L is excreted — over 99% is reabsorbed
Filtration fraction = GFR / Renal plasma flow = 125/625 = 20%
Renal blood flow 1200 mL/min = 20–25% of cardiac output

The Glomerular Filtration Barrier

Layer	Feature	Barrier to
1. Fenestrated endothelium	Pores 70–100 nm	Blood cells
2. Basement membrane	Type IV collagen + negatively charged heparan sulphate	Chief barrier — size and charge
3. Podocyte foot processes	Filtration slits 25 nm, bridged by nephrin	Proteins

Freely filtered — water, electrolytes, glucose, amino acids, urea, creatinine
Not filtered — cells, and proteins above 69,000 Da (albumin)
Negatively charged molecules are filtered less readily than neutral ones of the same size

Forces Governing Filtration (starling Forces)

Force	Value	Direction
Glomerular capillary hydrostatic pressure	60 mmHg	Favours filtration
Bowman's capsule hydrostatic pressure	18 mmHg	Opposes
Glomerular capillary oncotic pressure	32 mmHg	Opposes
Bowman's capsule oncotic pressure	0 (protein free)	—
Net filtration pressure	60 − (18 + 32) = 10 mmHg	Filtration

GFR = Kf × Net filtration pressurewhere Kf = filtration coefficient (permeability × surface area) = 12.5 mL/min/mmHg

Factors Affecting GFR

Factor	Effect on GFR
↑ Renal blood flow	↑
Afferent arteriolar constriction	↓
Efferent arteriolar constriction	↑ (mild) → ↓ if severe
↑ Plasma oncotic pressure (dehydration)	↓
↓ Plasma protein (nephrotic syndrome)	↑
Ureteric obstruction (↑ capsular pressure)	↓
↓ Kf (glomerulonephritis, diabetes)	↓
Sympathetic stimulation	↓

Autoregulation of GFR and Renal Blood Flow

GFR and renal blood flow are kept almost constant between mean arterial pressures of 80 and 180 mmHg

A. Myogenic mechanism

↑ BP → Afferent arteriole stretched → Smooth muscle contracts (myogenic response) → ↑ Resistance → Flow kept constant

B. Tubuloglomerular feedback

↑ GFR → ↑ NaCl delivery to distal tubule → Sensed by macula densa → Adenosine released → Afferent arteriolar constriction → GFR falls back to normal

Peculiarities of Renal Circulation

Two capillary beds in series — glomerular (high pressure, filtration) and peritubular (low pressure, reabsorption), joined by the efferent arteriole
Glomerular capillary pressure is 60 mmHg, far higher than the 17 mmHg of ordinary capillaries
Peritubular capillary pressure is 13 mmHg with a high oncotic pressure — strongly favouring reabsorption
Renal blood flow is autoregulated and is far in excess of metabolic need
Cortex receives 90% of renal blood flow; the medulla only 10%, which preserves the osmotic gradient but makes it vulnerable to ischaemia

Measurement of GFR

Inulin clearance — the gold standard; inulin is freely filtered, and neither reabsorbed nor secreted
Creatinine clearance — used clinically; slightly overestimates GFR because a little creatinine is secreted
Serum creatinine alone is insensitive — it rises only after GFR has fallen by about 50%

Applied Aspects

Acute glomerulonephritis → ↓ Kf → ↓ GFR → oliguria, oedema, hypertension
Nephrotic syndrome → loss of the negative charge barrier → selective albuminuria > 3.5 g/day
NSAIDs block prostaglandin-mediated afferent dilatation → may precipitate renal failure in hypovolaemia
ACE inhibitors dilate the efferent arteriole → ↓ intraglomerular pressure → renoprotective in diabetic nephropathy, but dangerous in bilateral renal artery stenosis

All questions in Renal System

Every Physiology chapter →