QBank notes: a profound realization about renal physiology

MSFP (mean system filling pressure) is controlled mainly by constriction of veins and venules. Although constriction of arterioles will increase blood pressure, there isn't enough volume in the arteriole system to significantly affect MSFP.

Patent foramen ovale versus Atrial septal defect. ASDs are much larger and can cause increased oxygen saturation on right side. A patent foramen ovale is of no hemodynamic significance.

----------

The granular cells (juxtaglomerular cells, modified pericytes of renal arteriole) secrete renin in response to:

• Beta1 adrenergic stimulation
• Decrease in renal perfusion pressure (detected directly by the granular cells)
• Decrease in NaCl absorption in the Macula Densa (often due to a decrease in glomerular filtration rate, or GFR).

Macula Densa Cells

Macula densa cells are columnar epithelium thickening of the distal tubule. The macula densa senses sodium chloride concentration in the distal tubule of the kidney and secretes a locally active (paracrine) vasopressor which acts on the adjacent afferent arteriole to decrease glomerular filtration rate (GFR), as part of the tubuloglomerular feedback loop.

A decrease in GFR means less solute in the tubular lumen. As the filtrate reaches the macula densa, less NaCl is re-absorbed. The macula densa cells detect lower concentrations in Na and Cl and upregulate Nitric Oxide Synthetase (NOS). NOS creates NO which catalyses the formation of prostaglandins. These prostaglandins diffuse to the granular cells and activate a prostaglandin specific Gs receptor. This receptor activates adenylate cyclase which increases levels of cAMP. cAMP augments renin release.

Note that the macula densa interprets higher NaCl concentration as a sign of wasteful loss of salt and as a signal to CONSERVE SALT by constricting the afferent arteriole and lowering GFR. However, the macula densa interprets a lower NaCl concentration as a sign of volume depletion due to salt wasting and a signal to CONSERVE SALT and WATER. This reflects an evolutionary past in which salt was not plentiful. The kidney is biased toward retaining salt! Unfortunately salt IS plentiful in the modern world; this predisposes to hypertension.