Renal Physiology

CHAPTER 33 Renal Physiology

Mary Ann C. Lim, MD

What are the 3 major functions of the kidneys?

1. First, the kidneys control the composition and volume of body fluids and maintain acid–base balance.

2. Second, blood is filtered in the glomerulus, forming a protein-free ultrafiltrate.

3. Third, the kidneys act as endocrine organs, producing hormones such as renin and erythropoietin (EPO), and produce active vitamin D₃.

What is the nephron and what are the different segments that comprise each one?

The kidney is composed of more than 1 million functional units called nephrons. Each nephron consists of the glomerulus contained within Bowman capsule, the proximal tubule, the loop of Henle, and the distal tubule, which ultimately drain into the collecting duct.

What are the cells that comprise the glomerulus?

The glomerulus is composed of a capillary network lined by endothelial cells, a central region of smooth musclelike mesangial cells, which provide structural support, and an outer layer of epithelial cells called podocytes.

What are the components of the glomerular filtration barrier?

Blood in the capillary lumen is filtered through the fenestrated endothelial cells, an intervening glomerular basement membrane, and the interdigitated foot processes of the podocytes separated by slit diaphragms, producing a cell- and protein-free ultrafiltrate within the lumen of Bowman capsule.

What prevents albumin from normally appearing in the urine?

Filtration of albumin is hindered by its size, which is restricted by the filtration barrier to molecules less than 42 Å, and by its negative charge, which is repelled by sialoglycoproteins on the glomerular basement membrane.

What percentage of total body weight is comprised by water and how is it distributed into different compartments?

Total body water (TBW) comprises 60% of total body weight, of which 40% is intracellular fluid and 20% is extracellular fluid (ECF, includes plasma and interstitial fluid).

Which electrolyte in the body regulates the volume of ECF?

Sodium is the major extracellular solute; hence the retention or excretion of Na⁺ by the kidneys is critical for the regulation of ECF volume. Sodium retention or increased oral intake leads to ECF volume expansion and Na⁺ loss leads to ECF volume depletion.

How does the kidney handle Na⁺ in the setting of congestive heart failure?

Congestive heart failure is a volume-excess state characterized by pulmonary and interstitial edema. However, the effective circulating volume in the body is decreased due to poor cardiac output and leads to low renal perfusion. This activates the renin–angiotensin system and the sympathetic nervous system, causing sodium retention; thus, further perpetuating the edema. Urine sodium levels are less than 10 mEq/dL. Sodium avidity is also seen in edematous states due to cirrhosis and nephrotic syndrome.

What is the kidney’s response to an increase in salt intake?

Increased Na⁺ intake leads to an increase in ECF volume. The renin—angiotensin system is inhibited and sympathetic tone is diminished. Atrial natriuretic peptide levels are elevated. These lead to decreased Na⁺ reabsorption and increased urinary Na⁺ loss or natriuresis.

What is the juxtaglomerular apparatus (JGA) and what are its functions?

The thick ascending limb of Henle loop comes into contact with the vascular pole (afferent and efferent arterioles) of its own glomerulus, forming the JGA. The JGA is important in the autoregulation of renal blood flow (RBF) and of the glomerular filtration rate (GFR). It also controls renin secretion.

What are the 3 cells types that make up the JGA and which ones control renin secretion?

Granular cells (also called juxtaglomerular cells), extraglomerular mesangial cells, and the macula densa cells. The macula densa cells of the JGA secrete renin.

How does the kidney maintain a relatively constant RBF and GFR?

The 2 mechanisms of autoregulation are the myogenic reflex and tubuloglomerular feedback. An increase in RBF will lead to vasoconstriction of the afferent arteriole caused by vascular smooth muscle contraction; thus decreasing flow. An increase in RBF will also enhance delivery of Na and Cl to the distal tubule. This is sensed by the macula densa, which will activate mechanisms that constrict the afferent arteriole.

What are the effects of activation of the renin–angiotensin–aldosterone system?

Renin stimulates angiotensin I (AI) production in the liver from angiotensinogen. Angiotensin-converting enzyme (ACE) converts AI to angiotensin II (AII). AII binds to AT₁ and AT₂ receptors, leading to systemic and efferent arteriolar vasoconstriction, increased Na⁺ reabsorption by the proximal tubule, and production of aldosterone by the zona glomerulosa cells of the adrenal cortex. Aldosterone leads to Na⁺ retention and K⁺ loss and metabolic alkalosis as a result of H⁺ secretion.

What are the effects of ACE inhibitors and angiotensin receptor blockers (ARBs)?

These drugs will decrease the glomerular filtration rate, decrease proteinuria, and lower systemic blood pressure. Hyperkalemia may result from decreased K⁺ loss caused by hypoaldosteronism.

How do nonsteroidal anti-inflammatory drugs (NSAIDs) affect the kidney?

NSAIDs inhibit cyclooxygenase, an enzyme important for the synthesis of vasodilatory prostaglandin E₂ and I₂ in the kidneys. Low prostaglandin levels will lead to vasoconstriction of the afferent arteriole, hence decreasing GFR, and to Na⁺ retention.

What are the effects of norepinephrine and dopamine on RBF?

Both afferent and efferent arterioles are innervated by sympathetic neurons. Norepinephrine constricts both and decreases RBF. Dopamine at low doses (up to 5 μg/kg/min when delivered exogenously) leads to vasodilation and increases RBF. At higher doses, it vasoconstricts the arterioles.

How good are serum urea and creatinine levels as surrogate measures of an individual’s GFR?

Urea is reabsorbed in the kidneys and creatinine is secreted by tubules. As a consequence, urea levels underestimate the GFR, whereas creatinine levels overestimate it. Tubular secretion of creatinine increases with worsening kidney function.

What factors are important to consider when using the serum creatinine levels to calculate creatinine clearance?

Two commonly used formulas are the Cockroft-Gault and modification of diet in renal disease (MDRD) equations. The Cockroft-Gault formula takes gender, weight, and age into account. The MDRD equation has race as an added variable.