17 - Glomerular Filtration and Tubular Function

Renal blood flow

20–25% of cardiac output goes to kidneys despite being ~0.5% body weight

Filtrate and urine production

~180 L, 1-2 litres of urine a day

Urine composition

Normally contains no protein, glucose, or bicarbonate

Renal corpuscle

Site of filtration in the nephron; includes glomerulus and glomerular capsule

Glomerulus

Capillary network that filters blood

Glomerular capsule

Surrounds glomerulus and captures filtrate

Renal tubule

Where renal filtrate is absorbed and secreted by tubular cells

Filtrate pathway

Afferent arteriole → renal corpuscle → efferent arteriole or renal tubule → collecting duct

renal corpuslce layers

glomerular capsule is lined by a partietal layer while the glomerulus is covered by a visceral layer

Juxtaglomerular apparatus

Regulates GFR using macula densa, granular cells, mesangial cells

Macula densa

Detects NaCl and releases adenosine to constrict afferent arteriole

Granular cells

Secrete renin

Mesangial cells

Have contractile properties and regulate filtration

what is filtration membrane made up of

• fenestrated endothelial cells

• basal lamina

• pedicels of podocytes that form filtration slits

Fenestrated capillaries

Has little holes to only allow water, ions, amino acids, etc. to come in

Basal lamina

Collagen fibers with negative charge to repel proteins to keep them in the blood and not in filtrate

Podocytes

Cells with pedicels forming filtration slits

how can filtration rate be altered

changing the blood pressure in the glomerulus or the leakiness of the capillaries/size of filtration slits

Changes in the glomerular blood pressure (and hence GFR) can be regulated by two intrinsic mechanisms:

• myogenic mechanism

• tubuloglomerular feedback

Myogenic mechanism

1. The smooth muscle of the afferent arteriole is stretched by the increase in blood pressure

2. Blood flow increases

3. Smooth muscle of afferent arteriole responds by contracting thus increasing resistance

4. Blood flow returns to normal

Tubuloglomerular feedback

Macula densa detects high flow → constricts afferent arteriole

Main hormones that regulate GFR

• angiotensin II

• ANP

Angiotensin II function steps

• Decrease in BP and SNS stimulation will signal juxtaglomerular apparatus to release renin

• Renin converts angiotensinogen to angiotensin I

• ACE converts angiotensin I to angiotensin II which causes the constriction of systemic and glomerular afferent arterioles

• Increase in blood pressure, bringing system back to homeostasis

ANP

• Released distension of the heart

• Increases GFR by relaxing mesangial cells

• Glomerular capillaries are more spread out so blood volume goes down

Completely reabsorbed substances in filtrate

Glucose, amino acids, bicarbonate

Partially reabsorbed substances in filtrate

Water, Na+, K+, Cl−

Excreted substances in filtrate

Urea, creatinine, drugs

Obligatory water reabsorption

90%, follows solute movement

Facultative water reabsorption

• Means it can increase or decrease depending on the amount required by the body, that is controlled by hormones

• 10%, regulated by ADH

by the end of the PCT, how much solute and water has been reabsorbed?

• 100% of the organic solutes have been rebasorbed

• 65% of the water has been reabsorbed

Paracellular transport in the tubules

Solutes slip between cells via tight junctions

Transcellular transport in the tubules

In and out of cells of the tubules following their electrochemical gradient

Secondary active transport

Uses energy of movement of ions down their concentration gradients to transport other solutes

Symporter

When the transport protein moves solutes in the same direction as the ions

Antiporter

When the transport protein moves solutes in the opposite direction

Co- transporters

• transport protein moves solutes in same and opposite directions

how does passive sodium reabsorption occur

through paracellular and transcellular route

how does active sodium reabsorption

Na/K ATPase

location of glucose reabsorption from filtrate

PCT

Glucose reabsorption how does it occur

• crosses apical membrane/brush border through a Na+/glucose symporter

• 2 Na+, 1 glucose

• Concentration of sodium must be high on the otuside and low on the inside for this to work

how does glucose cross the basolateral membrane to peritubular capillary

a facilitated diffusion transporter to cross from high to low concentration

how do kidneys regulate blood pH

• they use a Na+/H+ antiporter in the PCT

• H+ reacts with HCO3 to form carbonic acid and then carbonic anhydrase breaks it down into CO2 and H2O

Bicarbonate reabsorption

facilitated diffusion transport (basolateral membrane)

Na+/K+/2 Cl- Symporter location

• in the thick, ascending limb of the nephron loop which is a water impermeable area

• Cl and Na+ move from high to low concentration into the thick ascending limb cell to allow for water to follow and be reabsorbed