02.2 Physiological control of GFR and RBF

Physiological Control of Glomerular Filtration Rate and Renal Blood Flow

• This lecture discusses the mechanisms controlling glomerular filtration rate (GFR) and renal blood flow (RBF).
• It covers intrinsic control mechanisms (myogenic regulation and tubuloglomerular feedback) and extrinsic mechanisms involving the sympathetic nervous system and hormones.
• The goal is to maintain stable GFR and RBF despite variations in systemic blood pressure.

Learning Objectives

• Describe myogenic and tubuloglomerular feedback mechanisms, and their effect on urine volume and composition.
• Describe extrinsic mechanisms for controlling GFR.

Key Concepts and Definitions

• Autoregulation: The kidney's intrinsic ability to maintain stable GFR and RBF (80-180 mmHg) despite blood pressure changes.
• Myogenic Mechanism: An intrinsic property of vascular smooth muscle where stretching causes contraction and relaxation regulates afferent arteriole constriction/dilation to maintain GFR and RBF; crucial in protecting the kidneys from hypertension.
• Tubuloglomerular Feedback (TGF): A feedback loop between the macula densa of the juxtaglomerular apparatus (JGA) and the afferent arteriole that senses sodium chloride (NaCl) levels in the distal tubule to adjust afferent arteriole resistance and thus regulate GFR.

Clinical Applications

• Case Study Example: Hypertension patients benefit from understanding autoregulation, as the myogenic mechanism and TGF prevent excessive GFR increases, protecting kidney function.
• Diagnostic Approach: Renal function tests (GFR and urine NaCl concentration) assess autoregulatory function.
• Treatment Options: Managing blood pressure (e.g., ACE inhibitors) helps maintain autoregulation if hypertension or fluid overload is present.
• Complications/Management: Prolonged high blood pressure can damage kidneys, if autoregulation mechanisms fail. Treatment prioritizes controlling systemic blood pressure.

Pathophysiology

• Myogenic Mechanism: Increased blood pressure causes afferent arteriole constriction to prevent excessive increases in RBF and GFR; reduced pressure triggers vasodilation to maintain GFR.
• Tubuloglomerular Feedback: Increased NaCl in distal tubule triggers ATP and adenosine release; this causes afferent arteriole vasoconstriction and reduces GFR. Conversely, decreased NaCl results in vasodilation, and increased GFR. Nitric oxide (NO) reduces TGF, while angiotensin II enhances it.

Pharmacology

• ACE Inhibitors and ARBs: These drugs reduce afferent and efferent arteriole resistance, protecting against hypertension-induced damage by lowering GFR.
• Sympathetic Nervous System (SNS): The SNS influences GFR by vasoconstricting afferent arterioles, particularly during stress or emergencies, to maintain systemic blood pressure.

Differential Diagnosis

• Hypertension: High blood pressure can damage autoregulatory mechanisms; leading to impaired kidney function.
• Chronic Kidney Disease (CKD): Long-term autoregulation dysfunction contributes to progressive kidney disease.
• Acute Kidney Injury (AKI): In cases of shock or ischemia, the SNS can cause a reduction in GFR.

Investigations

• Renal Function Tests: Assess GFR and urine NaCl concentration to evaluate efficiency of autoregulation and rule out any damage.
• Blood Pressure Monitoring: Detects changes in autoregulation and risks for renal damage.

Summary and Key Takeaways

• Autoregulation maintains stable GFR and RBF between 80 and 180 mmHg via myogenic and tubuloglomerular feedback mechanisms.