Renal Physiology

The primary role of the kidneys is to filter the blood, allowing for the excretion of toxic substances in the urine.

– This is achieved through a functional unit called the nephron

– They kidneys produce 0.5-2 mL/kg/h urine –> 800-2000ml/day with a normal fluid intake of 2L per day.

One of the most important processes that occurs in the kidney is ultrafiltration

This is the movement of water and solute through a filter due to high pressure gradient, which occurs in the glomerulus, which is made of:

i) Fenestrated capillary membrane:

This has large pores which prevent passage of cells

 

ii) Basement membrane:

This is negatively charged and restricts the passage of large solutes

 

iii) Podocytes:

These have foot processes separated by filtration slits. This is the most restrictive layer that is negatively charged 

Together this filter usually restricts the passage of molecules >4nm in diameter (i.e. all cells and proteins)

– Only very small molecules like glucose and amino acids can pass through, but they are usually absorbed back.

Glomerular Filtration Rate (GFR)

The rate of filtration in the kidney is measured by the glomerular filtration rate

– If GFR falls too low –> leads to excessive reabsorption of solutes, low volume urine and hypertension

– If GFR is too high –> excessive loss of solutes and potential hypovolemia.

GFR = Kf [(Pc-PB) – σ(πcπB)]

The GFR is controlled by the difference in hydrostatic and oncotic pressure

Kf = filtration coefficient

This is the product of capillary permeability x membrane area.

– This can decrease if the filtration pores become blocked e.g. severe rhabdomyolysis releases myoglobin which blocks pores.

Pc = capillary hydrostatic pressure

This is the outward pressure of water in the capillary. It is primarily controlled in the kidney by the constriction of the afferent and efferent arteriole.

PB = tissue hydrostatic pressure

This is the inward forcing pressure of the interstitium

σ = colloid reflection coefficient 

At 1, this means there is total impermeability to protein. At 0, there is complete permeability, so proteins cannot exert their osmotic effect

πcB = oncotic pressure gradient

Only solutes that cannot cross the membrane easily are able to exert an osmotic force.

– This pressure helps pull water back into the capillary, opposing the hydrostatic pressure gradient.

Fluid balance

Fluid balance into tissues is determined by the Starling equation:  

Flow = Kf [(Pc-PB) – σ (πcπB)].

– The net filtration pressure changes along the capillary. This results in water movement out in early parts, and reabsorption in the later parts.

– The movement of water in and out of the blood is essential to maintain balance between different compartments:

The kidneys also have an active role in maintaining the blood pressure of the body, as they control water reabsorption and excretion.

– The kidneys receive 25% of the resting cardiac output, even though they only weigh 2%.

– Blood flows to the renal arteries –> interlobar arteries –> arcuate arteries –> interlobular arteries.

The Nephron

The functional unit of the kidney is the nephron.

This consists of the glomerulus, PCT, loop of Henle, DCT and Collecting Duct.

 

The amount of plasma filtered at the glomerulus is measured by the glomerular filtration rate (GFR)

–> Low GFR –> excessive reabsorption of solutes and low volume of urine

–> High GFR –> inadequate reabsorption of solutes.

Clearance

This is the theoretical volume of plasma which must be presented to the kidneys per unit time to provide the amount of substance found in the urine.

Clearance = rate of excretion/plasma concentration

 

If a substance is freely filtered, rate of filtration = GFR x plasma concentration

– If not reabsorbed or secreted then rate excretion = rate filtration –> hence clearance = GFR

 

Therefore, GFR can be measured by measuring the clearance of inulin (it is freely filtered, not reabsorbed)

a) But, a less accurate method is to measure creatinine, which is a breakdown product of creatine phosphate in skeletal muscle –> filtered, not reabsorbed and slowly secreted (gives 15% overestimate)

b) Therefore, GFR = rate of creatine excretion/plasma creatinine concentration.

c) As creatinine is proportional to muscle mass, requires correction for age, sex and weight to give the effective GFR (eGFR)

Reabsorption

The PCT reabsorbs 70% of the filtrate – it is water permeable, so water follows solute meaning reabsorption is isotonic.

– Glucose and amino acids are completely reabsorbed, so their concentrations in the filtrate are zero at the end of PCT.

 

Reabsorption is driven by the Na/K-ATPase which produces a Na+ gradient from the tubule to the cell.

– This allows uptake of glucose, amino acids and lactate against concentration gradient using a co-transporter.

– The movement of ions creates an osmotic gradient for water reabsorption.

 

Anion Cl- reabsorption is greater in the late PCT due to anion cycling.

– 2 Na+ ions are needed to reabsorb every molecule of glucose, using the SGLT-1 transporter and the GLUT-1 transporter in the basolateral membrane.

Secretion

Some organic anions and cations are actively secreted into the tubules. However different ions may compete for the same transporter, affecting rates of excretion.

Anions:

Prostaglandins, cAMP, Bile, Penicillin

Cations:

Creatinine, adrenaline, dopamine, morphine

Common Drugs:

Digoxin, Lithium, Methotrexate, Antibiotics (e.g. tetracyclines)