Lecture 1: Kidney Structure and Function I

Question 1

What is the function of the renal system?

Answer 1

Contributes to homeostasis by controlling →

1. Blood ionic composition
2. Blood pH
3. Blood volume
4. Blood pressure
5. Blood osmolarity
6. Excretion of waste
7. Hormone production
8. Glucose levels

Question 1

Describe the anatomical location of the kidney

Answer 1

• Kidney is posterior to the perineum (membrane that covers the abdominal cavity)
• Partially protected by the 11-12th rib

Question 2

What are the signs and symptoms of hypovolemia (dehydrated)?

Answer 2

• Symptoms: thirst, dizziness on standing, confusion
• Signs: low JVP, postural hypotension, weight loss, dry mucous membranes, reduced skin turgor, reduced urine output

Question 3

Hypovolemia cause

Answer 3

Too little regulation of body fluid volume

Question 4

Hypervolemia cause

Answer 4

Too much regulation of body fluid volume

Question 5

What are the signs and symptoms of hypervolemia (fluid overload)?

Answer 5

• Symptoms: ankle swelling, breathlessness
• Signs: raised JVP, oedema, weight gain, hypertension

Question 6

How do the kidneys regulate fluid balance?

Answer 6

• Kidneys regulate body fluid homeostasis
  
  • Regulate both volume n composition
• Altering plasma volume n composition → influences other fluid compartments
  
  • This is mainly done by changing extracellular sodium conc. and water → controls blood pressure

Question 7

Osmolarity

Answer 7

The measurement of solute concentration or osmotically active solutes

Question 8

Osmotic pressure

Answer 8

The pressure which needs to be applied to the solution to prevent an inward movement of fluid across a semi permeable membrane

Question 9

Oncotic pressure

Answer 9

The osmotic pressure exerted by the proteins in the blood plasma or exudate/filtrate which attracts/pulls water into the compartment

Question 10

Hydrostatic pressure

Answer 10

Force exerted by a fluid against a capillary wall

Question 11

Hypo-osmotic solution

Answer 11

Osmotic pressure outside > osmotic pressure inside

Question 12

Isotonic solution

Answer 12

High osmotic pressure outside = high osmotic pressure inside

Question 13

Hyperosmotic solution

Answer 13

Osmotic pressure outside > osmotic pressure inside

Question 14

How do the kidneys regulate body fluid homeostasis?

Answer 14

The kidneys play a major role in regulating body fluid homeostasis by:

1. Regulating Volume and Composition: They adjust the volume and composition of body fluids, including plasma, interstitial fluid, and intracellular fluid.
2. Altering Urine Volume: The kidneys regulate urine volume to control fluid balance in the body.
3. Adjusting Ionic Composition: They can change the concentrations of ions such as sodium, potassium, chloride, calcium, protons, bicarbonate, and phosphate ions in the extracellular fluid.
4. Influencing Blood Pressure: Regulation of extracellular sodium and water levels by the kidneys helps control blood pressure.
5. Linking to Other Fluid Compartments: Changes in plasma volume and composition by the kidneys influence the fluid balance in other compartments, such as interstitial and intracellular fluid.

Question 15

How does filtration occur in the kidneys?

Answer 15

1. Afferent Arteriole: Blood enters the glomerulus through the afferent arteriole.
2. High Hydrostatic Pressure: The afferent arteriole has a larger diameter compared to the efferent arteriole, leading to increased blood pressure within the glomerulus. This high hydrostatic pressure facilitates the movement of fluid out of the capillary.
3. Osmotic Pressure: The osmotic pressure within the capillary opposes filtration by drawing water back into the blood vessel.
4. Filtration: When the hydrostatic pressure (Pc) exceeds the opposing osmotic pressure, fluid is forced out of the capillary into the renal tubule. This process promotes plasma filtration, allowing small molecules and ions to pass through the filtration barrier into the renal tubules while retaining larger molecules like proteins and blood cells in the bloodstream

Question 16

How do hydrostatic pressure and oncotic pressure influence filtration in the kidneys?

Answer 16

• Hydrostatic pressure: force exerted by fluid against the walls of blood vessels, pushing fluid out of the capillaries.
• In the kidneys, high hydrostatic pressure in the glomerulus facilitates plasma filtration.
• Conversely, oncotic pressure (also known as colloid osmotic pressure) is the osmotic pressure exerted by proteins, such as albumin, in the blood vessel.
• Oncotic pressure draws fluid back into the capillaries. When hydrostatic pressure exceeds oncotic pressure, filtration occurs, allowing small molecules and ions to pass through the filtration barrier. However, if oncotic pressure exceeds hydrostatic pressure, fluid retention occurs, inhibiting filtration of plasma.

Question 17

Describe the anatomical structures and flow of fluid in the kidney.

Answer 17

• The kidney consists of the cortex, medulla, and renal pyramids.
• Fluid drains from the medulla into the calyx and then into the renal pelvis, which connects to the ureter.
• The functional unit of the kidney is the nephron, which is primarily located in the cortical region and has a granular appearance.
• Each nephron consists of a renal corpuscle (glomerulus and Bowman’s capsule) and a renal tubule (proximal convoluted tubule, loop of Henle, distal convoluted tubule, and collecting duct).
• Blood is filtered in the glomerulus, and the filtrate passes through the renal tubule, where substances are reabsorbed or secreted.
• The vasa recta are capillaries that surround the nephron, helping to maintain the osmotic gradient in the medulla.
• Finally, the collecting ducts drain into the minor calyx, major calyx, renal pelvis, ureter, and bladder.

Question 18

What are the components of a nephron and their functions?

Answer 18

• Renal corpuscle: Bowman’s capsule and the glomerulus, a tuft of capillaries nestled within Bowman’s capsule. Blood is filtered to produce the initial filtrate.
• Renal tubule:
  
  • PCT: reabsorbs water, ions, and nutrients from the filtrate
  • The loop of Henle: establishes a concentration gradient in the medulla
  • DCT: involved in further ion reabsorption and secretion, connects to the collecting duct.
• Collecting duct:
  
  • Receives filtrate from multiple nephrons and plays a crucial role in regulating water reabsorption and maintaining electrolyte balance.

Question 19

What are the two types of nephrons and how do they differ?

Answer 19

• Cortical nephrons:
  
  • Have a short loop of Henle.
• Juxtamedullary nephrons:
  
  • Have a longer loop of Henle.
  • Represent about 15% of all nephrons.
  • Produce highly concentrated urine due to their longer loop of Henle and the presence of a counter-current multiplier mechanism.

Question 20

Describe the flow of fluid in a juxtamedullary nephron.

Answer 20

• Fluid begins in the glomerular (Bowman’s) capsule.
• It then moves through the proximal convoluted tubule, descending limb of the nephron loop, thin ascending limb of the nephron loop, thick ascending limb of the nephron loop, and distal convoluted tubule.
• Finally, it drains into the collecting duct.

Question 21

What are the major processes involved in urine formation in the kidneys?

Answer 21

• Filtration:
  
  • Hydrostatic pressure pushes fluid out of the capillaries into the Bowman’s Capsule, forming the glomerular filtrate.
  • Glomerular filtration rate (GFR) is approximately 125 mL/min.
• Tubular reabsorption:
  
  • Occurs mainly in the proximal convoluted tubule (PCT) and loop of Henle.
  • About 99% of water, along with many ions, glucose, amino acids, urea, and other substances are reabsorbed back into the bloodstream.
• Tubular secretion:
  
  • Involves the transfer of materials from the blood into the renal tubule and duct cells to be excreted as waste.
  • Includes substances like drugs and metabolites.
• Urine excretion:
  
  • Kidneys produce urine containing waste products, excess ions, and other substances.
  • Urine exits the kidneys through the collecting ducts, into the calyces, renal pelvis, ureter, and finally out of the urethra.

Question 22

Describe the structural components and key cells involved in the renal corpuscle.

Answer 22

• Afferent and Efferent Arterioles:
  
  • Afferent: Brings blood toward the glomerulus.
  • Efferent: Carries blood away from the glomerulus.
• Bowman’s Capsule:
  
  • Surrounds the capillaries (glomerulus) and is the initial structure of the renal tubule.
• Glomerulus:
  
  • Network of capillaries where blood is filtered.
• Basement Membrane:
  
  • Single membrane around the capillaries.
• Mesangial Cells:
  
  • Contractile cells regulating glomerular filtration rate.
  • Unique to the glomerulus.
• Podocytes:
  
  • Epithelial cells of Bowman’s Capsule.
  • Have clear gaps crucial for filtration.
• Tubule:
  
  • Hollow tube surrounded by a single layer of epithelial cells.
• Juxtaglomerular Apparatus:
  
  • Sits between the afferent and efferent arterioles.
  • Involved in controlling glomerular filtration rate and releasing renin.
• Renin:
  
  • Released by the juxtaglomerular apparatus.
  • Important in controlling blood pressure and volume.
• Macula Densa Cells:
  
  • Part of the juxtaglomerular apparatus.
  • Sense the level of salt in the bloodstream.

Question 23

What triggers the secretion of renin by juxtaglomerular (JG) granular cells?

Answer 23

• Juxtaglomerular (JG) granular cells secrete renin in response to falls in extracellular fluid (ECF) volume or low sodium levels.
• Changes are detected by baroreceptors located around the body.
• The aim of this response is to increase sodium reabsorption, and consequently water reabsorption, to restore fluid balance.

Question 24

Describe the process of filtration in the renal corpuscle.

Answer 24

• Pushing of fluid and ions from the bloodstream into the nephrons through special capillaries that are much more leaky than typical capillaries.
• These capillaries have fenestrations that allow fluid to pass through but are small enough to prevent red blood cells and platelets from passing.
• The next layer after the capillaries is the basal membrane or lamina, which contains negatively charged proteins.
  
  • These proteins repel negatively charged particles, such as glycoproteins and albumin, from exiting the bloodstream.
• Spaces between the pedicels further facilitate the leakage of fluid due to hydrostatic pressure.

Question 25

Explain why filtration occurs to a greater extent in the renal corpuscle compared to other capillary beds in the body.

Answer 25

• The glomerular capillaries have a large surface area, which is regulated by mesangial cells, facilitating the filtration process.
• Endothelial membrane of these capillaries is thin and fenestrated, making it approximately 50 times leakier than other capillaries in the body.
• BP within the glomerular capillaries is much higher, primarily because of the differences in diameter between the afferent and efferent arterioles.
  
  • This higher blood pressure results in a significant hydrostatic pressure gradient, which forces fluid out of the capillaries into Bowman’s capsule and the renal tubule.

Question 26

What is the net filtration pressure in the context of kidney function, and how is it calculated?

Answer 26

• Net filtration pressure = glomerular blood hydrostatic pressure - capsular hydrostatic pressure - blood colloid osmotic pressure
  
  • GBHP: blood pressure, difference between afferent n efferent pressure, pressure pushing material out
  • CHP: pressure in the Bowman’s capsule, typically small
  • BCOP: pressure produced from proteins pulling fluid back via osmotic forces
• Net filtration pressure: total pressure that promotes filtration

Question 27

What are the three mechanisms that control glomerular filtration rate (GFR)?

Answer 27

1. Renal autoregulation
   
   1. Myogenic regulation: changes in blood vessel diameter regulate GFR
   2. Tubuloglomerular feedback: macula densa sensing changes in tubular fluid composition to adjust GFR.
2. Neuronal regulation (extrinsic, sympathetic): Sympathetic nervous system activity can influence GFR by altering arteriolar resistance.
3. Hormonal regulation (extrinsic): Hormones such as angiotensin II and atrial natriuretic peptide can modulate GFR through their effects on renal blood flow and arteriolar resistance.

Question 28

What is the myogenic control of glomerular filtration rate (GFR)?

Answer 28

• Kidneys maintain a constant renal blood flow and GFR in response to changes in blood pressure.
• When blood pressure increases → afferent arteriole walls stretch → smooth muscle cells in the juxtaglomerular (JG) apparatus contract.
• This contraction narrows the lumen of the arteriole → decrease in renal blood flow and GFR.
• Conversely, when blood pressure decreases, the opposite mechanism occurs, with the arteriole dilating to increase renal blood flow and GFR. This myogenic mechanism helps regulate GFR within a reasonable range in response to fluctuations in blood pressure.

Question 29

What is tubuloglomerular feedback and how does it regulate glomerular filtration rate (GFR)?

Answer 29

• Tubuloglomerular feedback is a negative feedback mechanism that regulates GFR through interactions between the macula densa cells, located between the afferent and efferent arterioles, and the juxtaglomerular apparatus (JGA).
• When blood pressure increases → GFR increase → the macula densa cells detect elevated sodium levels.
• This triggers constriction of the afferent arteriole.
• Increase in salt levels inhibits the release of nitric oxide, a vasodilator, leading to further constriction of the arteriole.
• These combined effects help reduce GFR.
• Conversely, when blood pressure decreases, resulting in reduced GFR, the decrease in salt levels is detected by the macula densa cells, leading to increased release of nitric oxide and vasodilation of the arteriole, thereby increasing GFR. This mechanism helps maintain GFR within a homeostatic range.

Question 30

Where does the majority of water reabsorption occur in the nephron, and which substances are typically absent in the urine as indicators of kidney function?

Answer 30

• The majority of water reabsorption occurs in the proximal (convoluted) tubule and the Loop of Henle within the nephron.
• Typically, urine should not contain proteins, glucose, or creatinine.
  
  • Presence in urine can indicate kidney dysfunction.
  • Specifically, the absence of proteins and glucose, and the stable levels of creatinine, are important indicators of normal kidney function.

Question 31

How is glucose reabsorbed in the renal tubules?

Answer 31

• Glucose reabsorption in the renal tubules primarily occurs in the PCT through sodium glucose transporters (SGLTs).
• At normal levels of plasma glucose, all glucose in the filtrate is reabsorbed via the PCT.
• Glucose is co-transported with sodium at the luminal membrane by a Na/glucose cotransporter. It then diffuses from the cell into the interstitial fluid and ultimately into the peritubular capillaries. This process requires ATP and involves glucose transporters such as GLUT1. As glucose reabsorption is an active process, it can become saturated when plasma glucose levels are high.

Question 32

What is the renal threshold for glucose and what happens if it is exceeded?

Answer 32

• Approximately 300 mg/100 mL of plasma.
• Beyond this threshold, glucose reabsorption in the renal tubules becomes saturated, meaning the transporters can’t remove glucose from the filtrate quickly enough.
• As a result, any excess glucose that surpasses the renal threshold starts to appear in the urine.
• Once the renal threshold is exceeded, there is a linear increase in the amount of glucose excreted in the urine.
  
  • This phenomenon is often used in diabetes testing, where glucose test strips detect the presence of glucose in the urine as an indicator of elevated blood sugar levels.

Question 33

Describe the process of sodium ion reabsorption and hydrogen ion secretion in the PCT

Answer 33

• Na+ Reabsorption: Na+ ions are primarily reabsorbed in the PCT.
  
  • They are co-transported with other substances, such as glucose and amino acids, across the luminal membrane of the tubule epithelial cells. This process depends on the Na+ gradient created by the activity of the sodium-potassium pump
• Secretion of Hydrogen Ions (H+): Na+ reabsorption is accompanied by the secretion of hydrogen ions (H+) into the tubular lumen.
  
  • This secretion helps maintain the acid-base balance in the body. Hydrogen ions are exchanged for Na+ ions via antiporters in the tubule epithelial cells.
• Exchange with Potassium (K+): Secretion of potassium ions (K+) into the tubular lumen.
  
  • This exchange helps regulate potassium balance in the body and is mediated by specific transporters.
• The distal part of the PCT is also involved in passive reabsorption of certain ions and urea. Passive reabsorption occurs based on concentration gradients, and water moves through osmosis to maintain osmotic balance.

Question 34

Describe the permeability and reabsorption characteristics of the descending and ascending limbs of the Loop of Henle.

Answer 34

• Descending Limb:
  
  • Permeable to water
    
    • Allows for the passive reabsorption of water into the interstitium, leading to concentration of the tubular fluid.
  • Approximately 15-20% of water is reabsorbed here as it passes through the tubule via osmosis.
• Ascending Limb:
  
  • Impermeable to water
  • Actively reabsorbs sodium, potassium and chloride ions via specific symporters present in the apical membrane of tubule epithelial cells.
  • This active transport mechanism creates a hypo-osmotic environment in the interstitium, facilitating further concentration of the tubular fluid as it moves towards the distal convoluted tubule

Question 35

What influences the amount of water and solute reabsorption in the late distal convoluted tubule (DCT) and collecting duct (CD)?

Answer 35

• The amount of water and solute reabsorption in the late DCT and CD varies depending on the body’s needs, primarily regulated by ADH.
• While reabsorption of water in the proximal tubule and loop of Henle occurs constitutively, the control of water reabsorption in the DCT and CD is flexible and can be modulated by ADH secretion.
• ADH levels determine the permeability of the collecting duct to water.
  
  • Dehydration: increased ADH secretion leads to enhanced water reabsorption in the DCT and CD → concentrated urine.
  • Fluid overload: reduced ADH secretion decreases water reabsorption → increased water excretion and dilute urine production.

Question 36

What stimulates the release of antidiuretic hormone (ADH) and how is it regulated?

Answer 36

• Released from the hypothalamus in response to changes in plasma osmolarity.
• Detection of increased plasma osmolarity can trigger several responses:
  
  • Enhanced thirst sensation to increase fluid intake.
  • Stimulation of ADH release from the posterior pituitary gland.
• The level of ADH in the bloodstream is also regulated by volume receptors located in various areas of the body:
  
  • Low-pressure sensors are found in the atria and pulmonary vasculature.
  • High-pressure sensors are located in the carotid sinuses and aortic arch.
  • Stretch receptors in the afferent arterioles, indirectly activated by the release of angiotensin II in response to reduced blood pressure or arteriolar stretch.
• Activation of these pressure and stretch receptors leads to the release of ADH, which plays a crucial role in regulating water reabsorption in the kidneys by increasing the permeability of the collecting ducts to water, thereby conserving water and concentrating urine.

Question 37

What are the main functions of antidiuretic hormone (ADH)?

Answer 37

• Reduce Water Excretion (Antidiuretic): ADH acts on the kidneys to increase the permeability of the collecting ducts and distal convoluted tubules → more water reabsorption → concentrate urine and reduce the excretion of water, conserving body fluids.
• Vasoconstriction:
  
  • ↓ in BP → ADH promotes vasoconstriction → increases blood volume and helps maintain an adequate blood pressure to ensure sufficient blood flow to vital organs.
• ADH is produced in the supraoptic and paraventricular nuclei of the hypothalamus, transported to the posterior pituitary, and released into the bloodstream when needed.
• Short plasma half-life allows for rapid adjustments in response to changes in the body’s fluid balance.
• The primary target sites of ADH action are the distal convoluted tubules and collecting ducts in the kidneys.

Question 38

How does antidiuretic hormone (ADH) increase water reabsorption in the collecting duct?

Answer 38

• ADH mediates the insertion of aquaporin-2 (AQP2) channels into the apical membrane of principal cells in the collecting duct.
• ↑ permeability of the collecting duct epithelium to water → enhanced water reabsorption.
• Upon binding of ADH to its receptors on the basolateral membrane of collecting duct cells, intracellular signaling pathways are activated.
• ADH activation →cAMP levels within the cell ↑ → PKA activated → AQP2 phosphorylated
  
  • AQP2-containing vesicles, facilitating their fusion with the apical membrane.
• As a result, more AQP2 channels are inserted into the apical membrane → increased water reabsorption from the urine filtrate.
• Nicotine reduces ADH absorption, potentially impacting water reabsorption in the collecting ducts.