Renal – Blood Flow

Master answer

Kidney

• Lie in the posterior wall of the abdomen – outside peritoneum (retroperitoneal)
• Each kidney approx 150g
• Medial side of each kidney = hilum
  • Renal artery and vein
  • Lymphatic supply
  • Nerves
  • Ureter
• Kidney surrounded by tough fibrous capsule
• Kidney organized into outer cortex and inner medulla
• Medulla
  • Organised into mutliple pyramids with the base at the corticomedullary junction and apices – the papilla – at the hilum draining into the ureters
• Nephrons = functional unit of the kidney (1 million / kidney)

Nephron

The functional unit of the kidney (1 million / kidney)

Parts:

• Afferent Arteriole: Brings blood to glomerulus. Regulate BP and supply blood to kidneys. Diameter bigger than Efferent Arterioles
• Efferent arteriole: Carries blood away. Regulates GFR
• Glomerulus: Provides driving force for solutes and water
• Bowman’s Capsule: Inner visceral layer, outer parietal layer. Filters bloods
• Renal Tubule: Filled with tubular fluid: aids in excretion and reabsorption
  • Proximal convoluted tubule
  • Loop of Henle:
    • Descending Limb
    • Lower thin Ascending limb
    • Thick Ascending Limb
  • Distal convoluted tubule
  • Connecting tubule

Types by length:

• Cortical nephrons
  • High in cortex, short loops of Henle.
• Juxtamedullary nephrons
  • Low in cortex near medulla, long loops of Henle which penetrate medulla
  • Only nephrons with vasa recta

Renal Blood Supply

• Renal blood flow ~1.25L/min (24% of cardiac output or 500ml/100g tissue/min) via renal artery
• 95% blood flow to cortex, ~5% to Medulla

• Renal artery enters through hilum it divides
  • → interlobar arteries
  • → arcuate arteries
  • → interlobular arteries
  • → afferent arterioles
  • → glomerular capillaries
  • → efferent arterioles
  • → peritubular capillaries
    • Peritubular capillaries supply blood to the renal tubules
    • Juxtaglomerular capillaries have specialized vasa recta which supply the LoH and is important in renal concentration of urine
• → venous system → interlobular veins → arcuate veins → interlobar veins → renal vein

Juxtaglomerular Apparatus

Formed where the TAL of LoH and DCT passes between the afferent and efferent
arterioles at the vascular pole of the glomerulus.
Comprises of:

• Macula Densa
  • Modified tubular epithelial wall of the DCT (located at the angle between
    afferent and efferent arterioles)
  • Contains specialised cells that sense changes in the filtrate NaCl levels →
    involved in intrinsic regulation of GFR and RBF by “Tubuloglomerular
    feedback” and control of renin secretion
• Juxtaglomerular (Granular) cells
  • Specialised smooth muscle cells found in the afferent arteriolar wall (esp
    “media”) that possess:
    • Renin-containing granules → secreted to invoke RAAS
    • Intrarenal-baroreceptors → involved in intrinsic autoregulation of RBF/GFR by a myogenic mechanism
• Extraglomerular mesangial (Lacis) cells
  • Participate in a signalling pathway of the Tubuloglomerular feedback
  • Possess contractile elements (actin and myosin) → contract in response to SNS stimulation → thereby ↓ glomerular surface area and GFR

JC / Sakurai 2019

Regulation of Renal Blood Flow

• Renal blood flow Autoregulated between 80~170mmHg
  • Blood flow maintained by modulating resistance based on pressure
• Renal vascular resistance maintained by interlobular arteries, afferent arterioles and efferent arterioles, amenable to external regulation
• GFR approx 180l/day – Autoregulated by tubuloglomerular feedback – relatively constant in response to fluctuating renal blood flow
  

INTRINSIC Regulation (Autoregulation) of GFR and RBF:

• Renal blood flow (and consequently GFR) Autoregulated between MAP range of 75~170mmHg
• Blood flow maintained by modulating resistance of AFFERENT based on pressure
• Efferent arteriole is NOT involved in autoregulation!
• Autoregulation of GFR and RBF can be overridden by external influences (Eg. hormones and SNS neurons), even when renal perfusion pressure is between MAP 75-170 mmHg!

Mechanisms of Autoregulation:

1. Myogenic autoregulation (Myogenic stretch response):­
   • In response to vascular wall stretch (due to increased intraluminal pressures), stretch dependent Ca influx occurs causing vasoconstricion of arterioles → increased resistance according to Poisuille-Hagen Equation → Decreased flow
   • In response to shear stress (due to increased flow), Endothelial derived relaxation factors released (such as NO) → NO acts on guanylyl cyclase → increased cGMP → smooth muscle relaxation → arteriolar vasodilation
2. Tubuloglomerular feedback (TGF)
   • Negative feedback – Links the rate of GFR to concentration of salt in tubular fluid at macula densa
   • Macula densa in wall of Ascending limb of loop of Henle Detects change in tubular flow (by the changing salt concentrations)
   • As a consequence of decreased blood flow → GFR decreases → Tubular flow rate decreases → Increased uptake of [Na] in Ascending LoH → Reduced [Na+] and [Cl-] reaching the DCT and macula densa → Juxtaglomerular apparatus releases prostaglandins (PGE2) → vasodilation of afferent arteriole → increased resistance to glomerular blood flow
   • With increased GFR → Increased tubular flow rate → Decreased [Na] uptake by the LoH → Increased [Na+] in macula densa → Juxtaglomerular apparatus secretes adenosine → Vasoconstriction of the afferent arteriole → Decreased blood flow

Note: Flow to Juxtamedullary nephrons is not autoregulated. High blood pressure increases juxtamedullary flow, increasing GFR and impairing renal concentration, resulting in a pressure diuresis.

Extrinsic Control of GFR and RBF:

1. Hormonal regulation of blood flow
   • Afferent arterioles:
     • Dilation → PGE-2, PGI-2, DA, ANP, NO, kinins
     • Constriction → High dose AII, NAd, ET-1, Adenosine, ADH, Thirst
   • Efferent arterioles:
     • Dilation → Inhibition of AT-II
     • Constriction → Low dose AT-II
   • Mesangial cell → Contracts due to AT-II, ADH and NAd (contraction response inhibited by ANP, DA, PGE2, PGI2)
   • Note: Angiotensin II:
     • At physiological (low) doses → it maintains GFR by efferent arteriolar vasoconstriction (at expense of RBF)
     • With ↑ AT-II levels → causes:
       • BOTH afferent and efferent arterioles constriction→ ↓ GFR
         and RBF
       • Mesangial cell contraction in renal corpuscle → ↓ KF → ↓
         GFR
2. Neural regulation of renal blood flow (SNS, noradrenergic)
   • All renal vescles richly innervated by sympathetic nerves
   • 2 Mechanisms:
     • Constricts BOTH afferent and efferent arterioles → ↓ RBF >>> GFR
     • Stimulates renin secretion (via β1 receptors on JG cells) → ↑ Angiotensin II production → afferent and efferent arteriolar vasoconstriction → ↓ RBF and GFR
3. Starling resistors
   • Increased intra-abdominal pressure will decrease blood flow in starling resistor model
   • Increased intra-capsular pressure will decrease renal blood flow
4. High blood amino acid/ glucose level
   • High filtered AA/ glucose load → reabsorption in PT with Na → ↓NaCl reaches distal tubules → macula densa → ↓adenosine → vasodilation → ↑RBF

JC / Mooney / Sakurai 2019

Answer by JC, Mooney, Sakurai