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Chapter 17

659

 

 

Basic science of relevance to urological practice

Physiology of bladder and urethra 660

Renal anatomy: renal blood flow and renal function 661 Renal physiology: regulation of water balance 664 Renal physiology: regulation of sodium and potassium

excretion 665

Renal physiology: acid–base balance 666

660 CHAPTER 17 Basic science in urological practice

Physiology of bladder and urethra

Bladder

The bladder consists of an endothelial lining (urothelium) on a connective tissue base (lamina propria), surrounded by smooth muscle (the detrusor), with an outer connective tissue, adventitia.

The urothelium consists of a multilayered transitional epithelium. It has numerous tight junctions that render it impermeable to water and solutes. The detrusor muscle is a homogeneous mass of smooth muscle bundles.

The bladder base is known as the trigone—a triangular area with the two ureteric orifices and the internal urinary meatus forming the corners. Intravesical pressure during filling is low. The main excitatory input to the bladder is via parasympathetic innervation (S2–4; cholinergic postganglionic fibers that when activated cause contraction; see p. 500).

Urethra

The bladder neck is normally closed during filling. It is composed of a circular smooth muscle (sympathetic innervation). High pressure is generated at the midpoint of the urethra in women, and at the level of the membranous urethra in men, where the urethral wall is composed of a longitudinal and circular smooth muscle coat, surrounded by striated muscle (external sphincter).

The striated part of the sphincter receives motor innervation from the somatic pudendal nerve (S3,4) and has voluntary control (ACh, or acetylcholinesterase mediates contraction).

The smooth muscle component of the sphincter has myogenic tone and receives excitatory and inhibitory innervation from the autonomic nervous system. Contraction is enhanced by sympathetic input (noradrenaline) and ACh. Inhibitory innervation is nitrergic (nitric oxide).

Micturition

Voiding is mediated by the pontine micturition center in the brain. During urine storage, bladder neck and sphincter smooth muscle are constricted, and ganglia in the bladder wall are inhibited by sympathetic input, while somatic innervation causes contraction of the striated sphincter muscle. As the bladder fills, sensory nerves respond to stretch and send information about bladder filling to the CNS.

At a socially acceptable time, the voiding reflex is activated. Stimulation of detrusor smooth muscle by parasympathetic anticholinergic nerves causes the bladder to contract. Simultaneous activation of nitrergic nerves reduces the intraurethral pressure, inhibition of somatic input relaxes the striated sphincter muscle, and sympathetic inhibition causes coordinated bladder neck and sphincter smooth muscle relaxation, resulting in bladder emptying.

RENAL ANATOMY: RENAL BLOOD FLOW AND RENAL FUNCTION 661

Renal anatomy: renal blood flow and renal function

The kidneys and ureters lie within the retroperitoneum (literally behind the peritoneal cavity). The hila of the kidneys lie on the transpyloric plane (vertebral level—L1).

Each kidney is composed of a cortex, surrounding the medulla, which forms projections—papillae, which drain into cup-shaped epithelial-lined pouches called calyces (the calyx draining each papilla is known as a minor calyx, and several minor calyces coalesce to form a major calyx, several of which drain into the central renal pelvis).

The renal artery, which arises from the aorta at vertebral level L1/2, branches to form interlobar arteries, which in turn form arcuate arteries, and then cortical radial arteries from which the afferent arterioles are derived. Venous drainage occurs into the renal vein.

There are two capillary networks in each kidney—a glomerular capillary network (lying within Bowman’s capsule) that drains into a peritubular capillary network, surrounding the tubules (proximal tubule, loop of Henle, distal tubule, and collecting ducts).

The anterior relations of the right kidney are, from top to bottom, the suprarenal gland, the liver, and the hepatic flexure of the colon. Medially, anterior to the right renal pelvis is the second part of the duodenum.

The anterior relations of the left kidney are, from top to bottom, the suprarenal gland, the stomach, the spleen, and the splenic flexure of the colon. Medially lies the tail of the pancreas.

The posterior relations of both kidneys are, superiorly, the diaphragm and lower ribs and, inferiorly (from lateral to medial), transversus abdominis, quadratus lumborum, and psoas major.

Renal blood flow (RBF)

The kidneys represent <0.5% of body weight, but they receive 25% of cardiac output (~1300 mL/min through both kidneys; 650 mL/min per kidney). Combined blood flow in the two renal veins is about 1299 mL/min, and the difference in flow rates represents the urine production rate (i.e., ~1 mL/min).

Autoregulation of RBF

RBF is defined as the pressure difference between the renal artery and renal vein divided by the renal vascular resistance. The glomerular arterioles are the major determinants of vascular resistance.

RBF remains essentially constant over a range of perfusion pressures (~80–180 mmHg) (i.e., RBF is autoregulated).

Autoregulation requires no innervation and probably occurs via the following:

A myogenic mechanism (increased pressure in the afferent arterioles causes them to contract, thereby preventing a change in RBF)

Tubuloglomerular feedback—the flow rate of tubular fluid is sensed at the macula densa of the juxtaglomerular apparatus (JGA), and in some way this controls flow through the glomerulus to which the JGA is opposed.

662 CHAPTER 17 Basic science in urological practice

Other factors that influence RBF

Sympathetic nerves innervate the glomerular arterioles. A reduction in circulating volume (such as blood loss) can stimulate sympathetic

nerves, causing the release of NA (which acts on 1-adrenoceptors on the afferent arteriole) to cause vasoconstriction. This results in reduced RBF and GFR (glomerular filtration rate).

Angiotensin II constricts efferent arterioles and afferent arterioles and reduces RBF.

Antidiuretic hormone (ADH), ATP, and endothelin all cause vasoconstriction and reduce RBF and GFR.

Nitric oxide causes vasorelaxation and increases RBF.

Atrial natriuretic peptide (ANP) causes afferent arteriole dilatation and increases RBF and GFR.

Renal function

Each kidney has 1 million functional units, or nephrons (Fig. 17.1), the functional unit of the kidney consisting of a glomerular capillary network, surrounded by podocytes (epithelial cells) of Bowman’s capsule, which drains into a tubular system (proximal convoluted tubule, loop of Henle, distal convoluted tubule, collecting tube, and collecting duct) (Fig. 17.1).

Blood is delivered to the glomerular capillaries by an afferent arteriole and drained by an efferent arteriole. An ultrafiltrate of plasma is formed within the lumen of Bowman’s capsule, driven by Starling forces across the glomerular capillaries. Reabsorption of salt and water occurs in the proximal tubule, loop of Henle, distal tubule, and collecting ducts.

Clearance is the volume of plasma that is completely cleared of solute by the kidney per minute.

Glomerular filtration rate (GFR) is the clearance for any substance that is freely filtered and is neither reabsorbed, secreted, nor metabolized by the kidney.

Cortex

1

 

 

 

2

 

 

 

3

 

8

KEY:

 

 

 

 

 

 

7

 

1

Afferent and efferent arterioles

 

 

 

 

of the glomerulus

Outer

 

 

2

Bowman’s capsule

6

 

3

Proximal convoluted tubule

medulla

9

4

Loop of Henle (thin descending limb)

4

 

5

Loop of Henle (thin ascending limb)

 

 

 

6

Loop of Henle (thick ascending limb)

 

 

 

7

Distal convoluted tubule

Inner

 

 

8

Collecting tubule

 

 

9

Collecting duct

medulla

5

 

 

 

 

 

 

 

 

Figure 17.1 The nephron.

RENAL ANATOMY: RENAL BLOOD FLOW AND RENAL FUNCTION 663

For a substance that is freely filtered at the glomerulus, is neither secreted nor reabsorbed by the renal tubules, and is not metabolized (catabolized), clearance is equivalent to GFR. When a substance is both filtered at the glomerulus and secreted by the renal tubules, its clearance will be greater than GFR. When a substance is filtered at the glomerulus, but reabsorbed by the renal tubules, its clearance will be less than GFR.

GFR is directly related to RBF.

Experimentally, GFR can be accurately measured by measuring the clearance of inulin (a substance that is freely filtered by the glomerulus and is neither secreted nor reabsorbed by the kidneys). Thus, the volume of plasma from which in 1 minute the kidneys remove all inulin is equivalent to GFR. Normally about one-fifth (120 mL/min) of the plasma that flows through the glomerular capillaries (600 mL/min) is filtered.

Clinically, GFR is estimated using serum and urine creatinine, and is ~80–125 mL/min in an adult male and 75–115 mL/min in an adult female.

Clearance of a substance from the plasma can be expressed mathematically as

Clearance = U xV / P

where U is the concentration of a given substance in urine, P is its concentration in plasma, and V is the urine flow.

Clinically, a serum and 24-hour urine can be obtained to measure creatine clearance by the formula:

(Urine creatinine × total urine volume)

Clearance =

(plasma creatinine × time)

where time = 1440 minutes for a 24-hour urine collection

Alternatively, the eGFR (estimated GFR) is based on serum creatinine combined with other factors such as age, sex, and race is used more commonly than the 24-hour urine collection. Various on-line calculators are available for this eGFR calculation, such as http://www.nkdep.nih.gov/professionals/gfr_calculators/idms_con.htm.

The Modification of Diet in Renal Disease (MDRD) eGFR equation does not require weight as results are normalized to 1.732 body surface area (BSA), an accepted “average” adult BSA.1 The National Kidney Disease Education Program, sponsored by the NIH, recommends reporting estimated GFR values greater than or equal to 60 mL/min/1.73 m2 simply as “t60 mL/min/1.73 m2,” not an exact number.

eGFR (mL/min/1.73 m2) = 186 x (Scr)-1.154 x (Age)-0.203

x (0.742 if female) x (1.212 if African American) (conventional units)

1 Levey AS, Bosch JP, Lewis JB, et al. (1999). A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 130(6):461–470.