JG cells

**Location and structure** - JG cells are modified vascular smooth muscle cells, mainly in the tunica media of the afferent arteriole. A few are in the efferent arteriole. - They contain renin-filled secretory granules. - Together with the macula densa and extraglomerular mesangial (lacis/Goormaghtigh) cells, they form the juxtaglomerular apparatus (JGA).

**Function: renin secretion** Three main stimuli trigger renin release: 1. **Decreased renal perfusion pressure.** JG cells act as an intrarenal baroreceptor and sense decreased afferent arteriolar stretch. Causes include hypovolemia, hemorrhage, and renal artery stenosis. 2. **Sympathetic stimulation.** Norepinephrine acts on β1 receptors, which raise cAMP. This is why β-blockers lower renin. 3. **Decreased NaCl delivery to the macula densa.** The macula densa senses low NaCl in the distal tubule (via the Na-K-2Cl cotransporter, NKCC2). It signals the JG cells to release renin through prostaglandins (PGE2/PGI2) and nitric oxide (COX-2 and nNOS dependent).

Renin release is inhibited by: - Angiotensin II (negative feedback) - ANP - Increased afferent arteriolar pressure - Adenosine, acting on A1 receptors - High NaCl delivery to the macula densa

**RAAS cascade** - Renin is an enzyme (aspartyl protease). It cleaves angiotensinogen (made in the liver) to angiotensin I. - ACE (mainly in the lung endothelium) converts angiotensin I to angiotensin II. - Angiotensin II causes efferent arteriole constriction (which preserves GFR), systemic vasoconstriction via AT1, aldosterone release, ADH release, and increased proximal tubule Na⁺/H⁺ exchange. It also increases thirst. - Aldosterone acts on principal cells and increases Na⁺ reabsorption and K⁺ secretion. It increases H⁺ secretion by α-intercalated cells.

**Clinical correlations** - **Renal artery stenosis:** Decreased perfusion causes secondary hyperaldosteronism and renovascular hypertension. Findings include hypokalemia and metabolic alkalosis. ACE inhibitors or ARBs can precipitate acute kidney injury in bilateral stenosis, or in unilateral stenosis of a solitary kidney, because the efferent tone that maintains GFR is lost. - **Reninoma (JG cell tumor):** This is a rare renin-secreting tumor, seen in young adults. It causes severe hypertension, hypokalemia, and metabolic alkalosis, with high renin and high aldosterone (secondary hyperaldosteronism). - **Primary hyperaldosteronism (Conn syndrome):** Renin is low because of negative feedback. This contrasts with the high renin of renovascular disease and reninoma. - **Drugs:** β-blockers, direct renin inhibitors (aliskiren), and NSAIDs decrease renin release. NSAIDs act by blocking prostaglandins. Loop diuretics increase renin release because they block NKCC2 in the macula densa. - **Hyporeninemic hypoaldosteronism:** This is the cause of type 4 RTA in diabetic nephropathy. It presents with hyperkalemia and a non-anion gap metabolic acidosis.

**High-yield distinctions** - JG cells (renin) are different from macula densa cells (sensors of NaCl) and from extraglomerular mesangial cells. - Podocytes and mesangial cells are not the same as JG cells. - NSAIDs constrict the afferent arteriole by blocking vasodilatory prostaglandins, whereas ACE inhibitors and ARBs dilate the efferent arteriole.