Juxtaglomerular (JG) Apparatus

Anatomy and Location

Three Components

1. Macula Densa

• A plaque of specialized epithelial cells in the wall of the thick ascending limb of Henle at the point of contact with the glomerular vascular pole.
• Cells are narrower, taller, and more tightly packed than other distal tubule cells, with crowded, prominent nuclei ("macula densa" = dense spot).
• Anchored to a basement membrane that blends with the extraglomerular mesangial matrix.
• Cells are joined by tight junctions with low permeability and have prominent lateral intercellular spaces (width varies with functional state).
• Contain high levels of neuronal nitric oxide synthase (nNOS) and cyclooxygenase-2 (COX-2) - key enzymes in signaling.
• Function: Sense luminal Na+ and Cl- concentration to trigger tubuloglomerular feedback.

2. Juxtaglomerular (Granular) Cells

• Modified smooth muscle cells in the tunica media of the afferent arteriole (and sometimes the efferent arteriole), just as it enters the glomerulus.
• Replaced the typical elongated smooth muscle cells; have rounded nuclei, rough ER, Golgi complexes, and cytoplasmic secretory granules containing renin.
• Connected to extraglomerular mesangial cells, adjacent smooth muscle, and endothelial cells by gap junctions.
• Densely innervated by sympathetic nerve terminals.
• Under conditions demanding more renin (volume depletion, renal artery stenosis), upstream smooth muscle cells in the afferent arteriole can transform into additional granular cells ("recruitment").
• Function: Synthesize, store, and release renin into the interstitium by exocytosis.

3. Extraglomerular Mesangial Cells (Lacis Cells)

• Located at the junction between the afferent and efferent arterioles, adjacent to the macula densa.
• Heavily branched cells with processes interconnected by gap junctions and containing microfilament bundles.
• No blood vessels or lymphatics penetrate this solid cell-matrix complex.
• Share structural and functional similarities with intraglomerular mesangial cells (supportive, contractile, and phagocytic roles).
• Also contain renin in some species, though its significance there is unclear.

Functions

A. Tubuloglomerular Feedback (TGF) - GFR Autoregulation

B. Renin-Angiotensin-Aldosterone System (RAAS) Activation

• ↓ renal perfusion pressure (sensed by afferent arteriole baroreceptors - likely the JG cells themselves)
• ↓ NaCl at macula densa (signals low tubular flow/volume depletion)
• Sympathetic stimulation (β1 adrenoceptors on JG cells)
• Low circulating angiotensin II (loss of negative feedback)

JG cells → Renin (aspartyl protease)
         ↓
Angiotensinogen (plasma α2-globulin) → Angiotensin I (decapeptide)
         ↓ (ACE, in lung capillaries)
Angiotensin II (octapeptide - potent vasoconstrictor)
         ↓                              ↓
Systemic vasoconstriction         Adrenal cortex → Aldosterone
(↑ BP directly)                   → ↑ Na+ & H2O reabsorption in DCT/collecting tubules
                                   → ↑ blood volume → ↑ BP

Histological Features

Clinical Relevance

• Renovascular hypertension (e.g., renal artery stenosis): Reduced perfusion activates JG cells → ↑ renin → ↑ angiotensin II → hypertension. Treated with ACE inhibitors or angiotensin receptor blockers (ARBs).
• ACE inhibitors / ARBs: Block RAAS downstream of JG cells; used in hypertension, heart failure, diabetic nephropathy.
• Renin-secreting tumors (juxtaglomerular cell tumors / reninomas): Rare benign tumors causing severe hypertension and hypokalemia (via hyperaldosteronism).
• Bartter syndrome: Defective NaCl transport in the thick ascending limb mimics a state of chronic volume depletion → JGA is perpetually stimulated → excess renin/aldosterone.

• Comprehensive Clinical Nephrology, 7th Ed., pp. 31-32
• Junqueira's Basic Histology, 17e, pp. 974-976
• Histology: A Text and Atlas (Pawlina), 9th Ed., pp. 1886-1887
• Ganong's Review of Medical Physiology, 26th Ed., pp. 703-704