книги студ / color atlas of physiology 5th ed[1]. (a. despopoulos et al, thieme 2003)

Kidney Structure and Function

Three fundamental mechanisms characterize kidney function: (1) large quantities of water and solutes are filtered from the blood. (2) This primary urine enters the tubule, where most of it is reabsorbed, i.e., it exits the tubule and passes back into the blood. (3) Certain substances (e.g., toxins) are not only not reabsorbed but actively secreted into the tubule lumen. The non-reabsorbed residual filtrate is excreted together with the secreted substances in the final urine.

Functions: The kidneys (1) adjust salt and water excretion to maintain a constant extracellular fluid volume and osmolality; (2) they help to maintain acid-base homeostasis; (3) they eliminate end-products of metabolism and foreign substances while (4) preserving useful compounds (e.g., glucose) by reabsorption; (5) the produce hormones (e.g., erythropoietin) and hormone activators (renin), and (6) have metabolic functions (protein and peptide catabolism, gluconeogenesis, etc.).

Nephron Structure

Each kidney contains about 106 nephrons, each consisting of the malpighian body and the tubule. The malpighian body is located in the renal cortex (!A) and consists of a tuft of capillaries (glomerulus) surrounded by a double-walled capsule (Bowman’s capsule). The primary urine accumulates in the capsular space between its two layers (!B). Blood enters the glomerulus by an afferent arteriole (vas afferens) and exits via an efferent arteriole (vas efferens) from which the peritubular capillary network arises (!p. 150). The glomerular filter (!B) separates the blood side from the Bowman’s capsular space.

The glomerular filter comprises the fenestrated endothelium of the glomerular capillaries (50–100 nm pore size) followed by the basal membrane as the second layer and the visceral membrane of Bowman’s capsule on the urine side. The latter is formed by podocytes with numerous interdigitating footlike processes (pedicels). The slit-like spaces between them are covered by the slit membrane, the pores of which are about 5 nm in diameter. They are shaped

148by the protein nephrine, which is anchored to the cytoskeleton of the podocytes.

The proximal tubule (!A, dark green) is the longest part of a nephron (ca. 10 mm). Its twisted initial segment (proximal convoluted tubule, PCT; !A3) merges into a straight part, PST (pars recta; !A4).

The loop of Henle consists of a thick descending limb that extends into the renal medulla (!A4 = PST), a thin descending limb (!A5), a thin ascending limb (only in juxtamedullary nephrons which have long loops), and a thick ascending limb, TAL (!A6). It contains the macula densa (!p. 184), a group of specialized cells that closely communicate with the glomerulus of the respective nephron. Only about 20% of all Henle’s loops (those of the deep juxtamedullary nephrons) are long enough to penetrate into the inner medulla. Cortical nephrons have shorter loops (!A and p. 150).

The distal tubule (!A, grayish green) has an

initially straight part (= TAL of Henle’s loop;

!A6) that merges with a convoluted part (distal convoluted tubule, DCT; !A7).

The DCT merges with a connecting tubule (!A8). Many of them lead into a collecting duct, CD (!A9) which extends through the renal cortex (cortical CD) and medulla (medullary CD). At the renal papilla the collecting ducts opens in the renal pelvis. From there, the urine (propelled by peristaltic contractions) passes via the ureter into the urinary bladder and, finally, into the urethra, through which the urine exits the body.

Micturition. Voiding of the bladder is controlled by reflexes. Filling of the bladder activates the smooth detrusor muscle of the bladder wall via stretch sensors and parasympa-

thetic neurons (S2–S4, !p. 78ff.). At low filling volumes, the wall relaxes via sympathetic neu-

rons (L1–L2) controlled by supraspinal centers (pons). At higher filling volumes (!0.3 L), the threshold pressure (about 1 kPa) that triggers the micturition reflex via a positive feedback loop is reached: The detrusor muscle contracts

!pressure"!contraction""and so on until the internal (smooth m.) and external sphincter

(striated m.) open so the urine can exit the body.

Renal Circulation

Around 90% of the renal blood supply goes to the cortex. Per gram of tissue, approximately 5, 1.75 and 0.5 mL/min of blood pass through the cortex, external medulla, and internal medulla, respectively. The latter value is still higher than in most organs (!p. 213 A).

The kidney contains two types of nephrons that differ with respect to the features of their second network of capillaries (!A).

Cortical nephrons are supplied by peritubular capillaries (see above) and have short loops of Henle.

Juxtamedullary nephrons are located near the cortex-medulla junction. Their efferent arterioles give rise to relatively long (!40 mm), straight arterioles (vasa recta) that descend into the renal medulla. The vasa recta supply the renal medulla and can accompany long loops of Henle of juxtamedullary nephrons as far as the tip of the renal papilla (!p. 148). Their hairpin shape is important for the concentration of urine (!p. 164ff.).

Any change in blood distribution to these two

150types of nephrons affects NaCl excretion. Antidiuretic hormone (ADH) increases the GFR of the jux-

tamedullary nephrons.

Due to autoregulation of renal blood flow, only slight changes in renal plasma flow (RPF) and glomerular filtration rate (GFR) occur (even in a denervated kidney) when the systemic blood pressure fluctuates between 80 and about 180 mmHg (!C). Resistance in the interlobular arteries and afferent arterioles located upstream to the cortical glomeruli is automatically adjusted when the mean blood pressure changes (!B, C). If the blood pressure falls below about 80 mmHg, however, renal circulation and filtration will ultimately fail (!C). RBF and GFR can also be regulated independently by making isolated changes in the (serial) resistances of the afferent and efferent arterioles (!p. 152).

Non-invasive determination of RBF is possible if the renal plasma flow (RPF) is known (normally about 0.6 L/min). RPF is obtained by measuring the amount balance (Fick’s principle) of an intravenously injected test substance (e.g., p-aminohippurate, PAH) that is almost completely eliminated in the urine during one renal pass (PAH is filtered and highly secreted, !p. 156ff.). The eliminated amount of PAH is calculated as the arterial inflow of PAH into the kidney minus the venous flow of PAH out of the kidney per unit time.

where PaPAH is the arterial PAH conc., PrvPAH is the renal venous PAH. conc., UPAH is the urinary PAH conc., and VU is the urine output/time.

PrvPAH makes up only about 10% of the PaPAH and normally is not measured directly, but

This equation is only valid when the PaPAH is not too high. Otherwise, PAH secretion will be saturated and PAH clearance will be much smaller than RPF (!p. 161 A).

RBF is derived by inserting the known hematocrit (HCT) value (!p. 88) into the follow-

A.

Cortex

Medulla

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Plate 7.3 Glomerular Filtration and Clearance

Transport Processes at the Nephron

the proximal to the distal segments of the tubules.

Whereas permeability of the two membranes in series is decisive for transcellular transport (reabsorption, secretion), the tightness of tight junctions (!p. 18) determines the paracellular permeability of the epithelium for water and solutes that cross the epithelium by paracellular transport. The tight junctions in the proximal tubule are relatively permeable to water and small ions which, together with the large surface area of the cell membranes, makes the epithelium well equipped for paraand transcellular mass transport (!D, column 2). The thin limbs of Henle’s loop are relatively “leaky”, while the thick ascending limb and the rest of the tubule and collecting duct are “moderately tight” epithelia. The tighter epithelia can develop much higher transepithelial chemical and electrical gradients than “leaky” epithelia.

Measurement of reabsorption, secretion and excretion. Whether and to which degree a substance filtered by the glomerulus is reabsorbed or secreted at the tubule and collecting duct cannot be determined based on its urinary concentration alone as concentrations

creatinine) concentration ratio, Uin/Pin is a measure of the degree of water reabsorption. These substances can be used as indicators because they are neither reabsorbed nor secreted (!p. 152). Thus, changes in indicator concentration along the length of the tubule occur due to the H2O reabsorption alone (!A). If Uin/Pin = 200, the inulin concentration in the final urine is 200 times higher than in the original filtrate. This implies that fractional excretion of H2O (FEH2O) is 1/200 or 0.005 or 0.5% of the GFR. Determination of the concentration of a (freely filterable and perhaps additionally secreted) substance X in the same plasma and urine samples for which Uin/Pin was measured will yield Ux/Px. Considering Uin/Pin, the fractional excretion of X, FEX can be calculated as follows (!A and D, in % in column 5):

(!p. 152) when simplified for VU. The fractional reabsorption of X (FRX) is calculated as

7 Kidneys, Salt, and Water Balance

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D. Reabsorption, secretion and fractional excretion

Plate 7.5 Transport Processes at the Nephron II

157