Control and regulation of GFR and renal blood flow

• Sympathetic nervous system activation _decreases_ GFR.– Strong activation of renal sympathetic nerves

can constrict the renal arterioles and decrease renal blood flow and GFR.

• Only strong activation due to brain ischemia or hemorrhage.

– Mild activation has insignificant effect.

Control and regulation of GFR and renal blood flow

• Hormonal and autacoid control of renal circulation.• Norepinephrine, epinephrine, and endothelin constrict renal

blood vessels and decrease GFR.• Angiotensin II constricts efferent arterioles which helps to

prevent a decrease in glomerular hydrostatic pressure and GFR.– Decreased arterial pressure or low blood volume induce

angiotensin II production.» These effects normally decrease GFR

• Endothelial-derived NO decreases renal vascular resistance (induces dilation) and increases GFR.

• Prostaglandins increase renal blood flow and increase GFR.

Autoregulation of GFR and renal blood flow

• Mechanisms which maintains renal blood flow and GFR relatively constant despite changes in arterial blood pressure.

• Myogenic Mechanism

• Tubuloglomerular Feedback Mechanism.

Sherwood’s Human Physiology 14-12 5th Ed. & 14-11 6th Ed.

Autoregulation of GFR and renal blood flow

Sherwood’s Human Physiology 14-12 5th Ed. & 14-11 6th Ed.

Autoregulation of GFR and renal blood flow

• Myogenic Mechanism of GFR– Smooth muscle cells in the afferent arteriole

respond to changes in vascular pressure

– Increase in arterial pressure leads to _constriction

– Decrease in arterial pressure leads to _relaxation_

Sherwood’s Human Physiology 14-12 5th Ed. & 14-11 6th Ed.

Autoregulation of GFR and renal blood flow

• Tubuloglomerular Feedback Mechanism.

– Involves the Juxtaglomerular complex which is made up of juxta- glomerular cells from the afferent & efferent arterioles and specialized epithelial cells in the distal tubule called the macula densa .

Sherwood’s Human Physiology 14-12 5th Ed. & 14-11 6th Ed.

Autoregulation of GFR and renal blood flow

• Tubuloglomerular Feedback Mechanism.

– Juxtaglomerular cells (JG cells)• Mechanoreceptors• Modified smooth muscle cells that secrete

renin• Leads to efferent arteriole constriction

Sherwood’s Human Physiology 14-12 5th Ed. & 14-11 6th Ed.

Autoregulation of GFR and renal blood flow

• Tubuloglomerular Feedback Mechanism.– The macula densa senses changes in the Na+ &

Cl- content in the distal tubule which can be related to the flow rate through the tubule.

• Chemoreceptors

– A decreased flow rate results in less Na+ & Cl- in the proximal tubules and therefore less would be present in the distal tubule.

Sherwood’s Human Physiology 14-12 5th Ed. & 14-11 6th Ed.

Tubuloglomerular Feedback Mechanism.

Guyton’s Textbook of Medical Physiology 26-15

• Decreased Arterial Pressure or Decreased concentration of NaCl at the macula densa results in dilation of the afferent arterioles and increased renin release to increase the GFR back to normal.

↓ Arterial pressure

↓ Glomerular Hydrostatic pressure

↓ GFR

↓ Macula densa NaCl

Renin

Angiotensin II

efferentarteriole resistance

afferentarteriole resistance

Tubuloglomerular Feedback Mechanism.

Sherwood’s Human Physiology 14-13 5th Ed. & 14-12 6th Ed.

• Increased Arterial Pressure or Increased concentration of NaCl at the macula densa results in constriction of the afferent arterioles decrease the GFR back to normal.

↑ Arterial pressure

↑ Glomerular Hydrostatic pressure

↑ GFR

↑ Macula densa NaCl

Afferent arteriole constriction

↓ GFR hydrostatic pressure

↓ GFR to Normal

Tubular Reabsorption

Sherwood’s Human Physiology 14-17 5th Ed. & 14-14 6th Ed.

• For a substance to be reabsorbed it must first be transported across the tubular epithelial membrane into interstitial space and then through the peritubular capillary membrane into the blood.

Guyton’s Textbook of Medical Physiology 27-1

Tubular Reabsorption

• Water and solutes are transported via:– Transcellular route

– Paracellular route

– Bulk flow into the bloodstream

Sherwood’s Human Physiology 14-17 5th Ed. & 14-14 6th Ed.

Tubular Reabsorption

– Transcellular route• Substance needs to traverse 5 distinct barriers

– Paracellular route• Substance needs to traverse 3 distinct barriers

Guyton’s Textbook of Medical Physiology 27-1 & Sherwood’s Human Physiology 14-18 5th Ed & 14-15 6th Ed

Tubular Reabsorption

• Passive transport – Due to electrical and chemical gradient (Urea

and Cl-)

• Osmosis• Active transport

– Primary active transport Na+- K+-ATPase.

• Pinocytosis – Especially for reabsorption of proteins.