Chapter 12 Discussion questions and answers

Chapter 12

Kidney and Urinary Tract

ANSWERS TO DISCUSSION QUESTIONS

1. Discuss the structural features of the kidney nephron and describe how its structure relates to its function.

Answer
The basic unit of the kidney is the nephron. There are 800,000 to 1.5 million nephrons in each normal human kidney. Nephrons are composed of:

a) Renal corpuscle (comprising glomerulus and Bowman’s capsule)

b) Proximal convoluted tubule (PCT)

c) Descending loop of Henle

d) Ascending limb

e) Thick ascending limb

f) Distal convoluted tubule

g) Collecting duct

Their primary function is to control the homeostatic regulation of the blood. There are two general types of nephron, cortical and juxtamedullary. The definition is based on the length and location of their associated loop of Henle. Cortical nephrons have their loop of Henle in the renal medulla at the junction with the renal cortex, while in the case of the juxtamedullary nephrons the loop of Henle is located near the medulla but still within the cortex, hence the term juxtamedullary.

Give consideration to the distinctive features of the renal corpuscle:

  • The Bowman’s capsule is a double-walled sac structure with each wall consisting of a single layer of simple squamous epithelial cells (parietal layer). Broadly speaking, inside the Bowman’s capsule there are three layers as follows (from outside inwards):

a) Bowman’s space (capsular space). This is between the parietal and visceral layers. This is where the filtrates enter after passing through the filtration sites.

b) Visceral layer. This layer lies just above the glomerular basement membrane and is composed of cells called podocytes.

c) Filtration barrier. This layer is composed of the specialized fenestrated endothelium (which is porous).

2. Describe how homeostatic mechanisms of the kidney operate.

Answer
Consideration of the key functions should be highlighted:

  • Excretion of wastes
  • Resorption of nutrients
  • Acid-base balance
  • Hormone secretion /regulation
  • Hormone secretion /regulation: A number of hormones are secreted by the kidneys. The most common include eythropoietin and renin. Erythropoietin stimulates red blood cell formation in the bone marrow. Renin is an enzyme that is involved in the regulation of aldosterone levels within the body. Aldosterone is a steroid hormone produced by the outer section of the adrenal cortex. It is linked to the conservation of sodium, secretion of potassium, increased water retention and increased blood pressure. In addition, calcitriol, which is the activated form of vitamin D, stimulates osteoblasts to secrete interleukin (IL)-1, which then stimulates osteoclasts to increase bone resorption. The activated form of vitamin D is produced as a result of changes in Ca2+ in the bloodstream as a result of hydroxylation of vitamin D. Prostaglandins are hormones derived from the metabolism of arachidonic acid, and are produced in various cells of the kidney; examples are PGE2 and prostacyclin. They have important roles within the kidney in ensuring renal function; however, they have little systemic activity as they are rapidly metabolized once in pulmonary circulation.
  • Regulation of blood pressure: Although not primary regulators of blood pressure, long-term regulation is related to kidney activity. This involves the maintenance of the extracellular fluids and in particular the plasma sodium concentration. Renin is also involved here as it acts as a chemical messenger in the renin- angiotensin system (RAS). Principally, changes in renin, secreted by the juxtaglomerular cells, alters the levels of angiotensin II and aldosterone. Both of these hormones, via complex mechanisms, increase the absorption of sodium chloride within the kidneys, resulting in the expansion of the extracellular fluid domains and a rise in blood pressure. Thus, when renin levels are high the levels of angiotensin II and aldosterone increase, resulting in increased sodium chloride resorption and expansion of the extracellular fluid domains, resulting in increased blood pressure. Conversely, when renin levels are low the levels of angiotensin II and aldosterone decrease, resulting in the contraction of the extracellular fluid domain spaces and a subsequent decrease in blood pressure.
  • Osmolarity regulation: plasma osmolarity is regulated by the hypothalamus in the brain, which in turn communicates with the posterior pituitary gland. The increase in osmolarity causes the release of antidiuretic hormone (ADH). As a result, water is resorbed by the kidneys and urine concentration increases. The ADH binds to cells within the collecting ducts of the kidney that translocate the membranes via aquaporins and allow normally impermeable membranes to become permeable, resulting in loss of water from the collecting duct cells which is resorbed into the body via the vasa recta.

    The hyperosmotic function of the kidney is generally regulated by two principal mechanisms:

Recycling of urea: When plasma volume is low and ADH is released, the aquaporins not only become permeable to water but also urea. This enables the urea to leave the collecting duct and enter the medulla of the kidney, creating a hyperosmotic solution that attracts water. The urea can then re-enter the nephron and be excreted or recycled depending on ADH level.

Single effect: This process is dependent on the fact the ascending thick limb of the loop of Henle is nor permeable to water but is permeable to sodium chloride (NaCl). This creates a countercurrent exchange system in which the medulla of the kidney becomes concentrated in ions, in turn setting up an osmotic gradient for water to flow through the aquaporins of the collecting duct opened by ADH.

  • Miscellaneous functions:

Gluconeogenesis: During periods of prolonged fasting, the kidneys synthesize glucose from amino acids; a process termed gluconeogenesis. This process primarily involves the liver but the kidneys and small intestine also play important roles.
Contribution to the production of amniotic fluid in pregnancy: Until fetal kidneys start work during the fourth month of gestation, the amniotic fluid is produced by the mother’s body. Subsequently, the fetus contributes to the amniotic fluid by urination.

The kidneys and urinary system achieve homeostatic regulation independently in some cases, such as in processes involving simple filtration, resorption and secretion, but also in association with the endocrine system and its hormones such as renin, angiotensin II, aldosterone and antidiuretic hormone.

3. Discuss the structure of the glomerulus and how important is it to the integrity of the kidney as a functioning unit in health and disease.

Answer
The glomerulus is a network of capillaries lying within the Bowman’s capsule, the entering blood vessel being wider than the exiting vessel. It is within the glomerulus that the blood is filtered. The glomerular membrane contains pores that are large enough for small molecules to pass through but small enough to retain large molecules and red blood cells. The blood arrives in the glomerulus via the afferent arteriole under considerable pressure.
The glomerular wall consists of squamous epithelium which appears to be fenestrated (window like). It is through these ‘windows’ that the glomerular filtrate passes into the Bowman’s capsule. Various pathological conditions can result if these membranes are damaged. The membrane therefore acts to keep large macromolecules and cells within the bloodstream. This explains why it is not normal to find blood in urine.

The glomerular basement membrane consists of three components:

  • The glomerular capillary endothelium
  • Basal layer
  • Podocytes

The glomerular capillary endothelium contains fenestrations which are not supported by a spanning diaphragm. These pores (fenestrations) are 70–100 nm in diameter, which as actually quite large! They need to be this size in order to allow the free filtration of fluid containing plasma and associated proteins, but small enough to stop the transfer of red blood cells. As red blood cells are around 6–8 μm in diameter, they are unable to pass through these pores.

The basal layer can be divided into three further sublayers:

  • The lamina rara externa (adjacent to the podocyte processes), composed largely of heparan sulphate
  • The lamina densa (the darker zone within the basement membrane complex) composed largely of type 4 collagen and laminin
  • The lamina rara interna (adjacent to the endothelial cells), again composed largely of heparan sulphate.

There are various autoimmune states that affect the kidney and which directly attack the structures that make up the glomerulus. These conditions involve the deposition of immune complexes at and around the glomerular basement membranes. This directly affects the kidney’s functional ability, particularly in relation to filtration rates.

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