Chapter 6 Renal Physiology
(From Feehally J, Floege J, Johnson RJ: Comprehensive Clinical Nephrology, 3rd ed. Philadelphia, Mosby, 2007, Fig. 1-2.)
(From Bargmann W: Histologie und Mikronscopische Anatomie des Menschen. Stuttgart, Germany, Georg Thieme, 1977, p 86.)
(From Mount DB, Pollak MR: Molecular and Genetic Basis of Renal Disease. Philadelphia, Saunders, 2008, Fig. 21-2B.)
Pathology note: In a condition known as minimal change disease (lipoid nephrosis), the negative charges on the glomerular filtration barrier are lost for unknown reasons. Certain proteins are then able to pass through the basement membrane, resulting in proteinuria. This disease is the most common cause of the nephrotic syndrome (loss of >3.5 g of protein per day into the urine) in children and is usually responsive to treatment with corticosteroids. Of note, the positively charged immunoglobulin light chains, which are overproduced in multiple myeloma, are small enough to pass through the glomerular filtration barrier (and therefore into the urine) without any pathologic changes in the glomerulus. Therefore, if one suspects a paraproteinemia or multiple myeloma, a negative urine dipstick (which detects negatively charged proteins) does not rule out such a diagnosis. In these cases, precipitation of all proteins in the urine can be performed with sulfosalicylic acid (SSA); this will detect the presence of globulins and Bence-Jones proteins.
(From Koeppen BM, Stanton BA: Berne and Levy Physiology, 6th ed. Updated ed. Philadelphia, Mosby, 2010, Fig. 32-17.)
Clinical note: In the presence of a damaged basement membrane (e.g., membranous nephropathy), where protein can be filtered across the glomerular membrane, the resulting increase in oncotic pressure in Bowman space can result in an elevated NFP and increased filtrate production. Review of systems in such patients with nephrotic syndrome may be significant for the presence of foamy or frothy urine due to the lowering of surface tension by the severe proteinuria.
(From Oh W, Guignard J-P, Baumgart S: Nephrology and Fluid/Electrolyte Physiology: Neonatology Questions and Controversies. Philadelphia, Saunders, 2008, Fig. 5-3.)
(Modified from Rose BD, Rennke KG: Renal Pathophysiology: The Essentials. Baltimore, Williams & Wilkins, 1994.)
Clinical note: Narrowing of the renal arteries (renal artery stenosis) most commonly occurs as a result of atherosclerosis or fibromuscular hyperplasia. In unilateral renal artery stenosis, hypertension may occur because decreased perfusion of the affected kidney is incorrectly “interpreted” as intravascular volume depletion, which triggers a neurohormonal cascade response (the renin-angiotensin-aldosterone system and antidiuretic hormone [ADH]; see Chapter 3), causing fluid retention and vasoconstriction resulting in hypertension. When both renal arteries are affected (bilateral renal artery stenosis), renal blood flow may become so compromised that the kidneys are unable to perform their normal recycling functions, resulting in the toxic accumulation of metabolic byproducts.
6-9 Tubuloglomerular feedback. Because of the hairpin loop structure of each nephron, the macula densa is located adjacent to its originating glomerulus and is positioned adjacent to the afferent and efferent arterioles that supply that glomerulus. GFR, Glomerular filtration rate; JGA, juxtaglomerular apparatus.
(From Koeppen BM, Stanton BA: Berne and Levy Physiology, 6th ed. Updated ed. Philadelphia, Mosby, 2010, Fig. 32-19.)
Pharmacology note: The juxtaglomerular apparatus is informed of NaCl in the tubular lumen by virtue of its transport into the cells of the macula densa by the same Na+-K+-2Cl− cotransporter that is inhibited by loop diuretics. One reason for the potency of loop diuretics is their ability to blunt tubuloglomerular feedback and thereby maintain GFR (and urine production) despite increased NaCl traffic past the macula densa.
Clinical note: Acute tubular necrosis (ATN) is a common cause of acute renal failure, which results when hypotension (ischemia, hypoxemia) or tubular toxins damage renal tubular epithelial cells. In ATN, owing to dysfunction of these cells, sodium and water reabsorption in the proximal tubule, where most of the NaCl and fluid reabsorption normally occurs, is impaired. Large amounts of NaCl and water are therefore presented to the macula densa. Through tubuloglomerular feedback, this decreases renal blood flow and GFR by stimulating vasoconstriction of the afferent arteriole. The subsequent decrease in GFR, despite causing acute renal failure, may play a role in limiting potentially life-threatening losses of sodium and water that might otherwise occur in ATN.
(From Koeppen BM, Stanton BA: Berne and Levy Physiology, 6th ed. Updated ed. Philadelphia, Mosby, 2010, Fig. 32-13.)
Clinical note: Because measuring renal clearance involves collecting urine and is a nuisance for patients, plasma creatinine concentration is usually measured as a surrogate marker of renal function. However, because the plasma creatinine concentration is dependent on both muscle mass and renal function, this method may significantly overestimate renal function in patients with reduced muscle mass and, hence, lower creatinine production. Similarly, renal function may be underestimated in very muscular individuals and in situations, such as crush injury, in which extensive muscle damage leads to increased creatinine release into the circulation.
(From Boron W, Boulpaep E: Medical Physiology, 2nd ed. Philadelphia, Saunders, 2009, Fig. 33-8.)
6-12 Because of the reabsorption of water, the tubular fluid concentration of inulin increases roughly threefold compared with plasma concentration along the proximal convoluted tubule (PCT). Because inulin is neither secreted nor reabsorbed, substances that become concentrated more than inulin (e.g., PAH) must therefore be secreted, and substances that becomes less concentrated than inulin (e.g., urea) must be reabsorbed. PAH, Para-aminohippuric acid; [P], plasma concentration; [TF], tubular fluid concentration.
|Substance||Approximate Clearance Rate (as % of GFR)|
GFR, Glomerular filtration rate.