Lecture 12
Lecture 13
Lecture 14
Lecture 15
Lecture 16
100

List two substances that normally pass into the filtrate at the glomerulus.

Two substances that normally pass into the filtrate at the glomerulus are:

  • Glucose
  • Urea
100

Describe the main difference in water permeability between the descending and ascending limbs of the nephron loop.


The descending limb of the nephron loop is highly permeable to water (due to aquaporins) but relatively impermeable to solutes, so water leaves the tubule by osmosis and the filtrate becomes more concentrated.

In contrast, the ascending limb (especially the thick ascending limb) is impermeable to water but actively reabsorbs solutes like Na⁺, K⁺, and Cl⁻, so the filtrate becomes more dilute as it moves upward.

100

Define glycosuria and name the most likely associated condition.

Glycosuria is the presence of glucose in the urine, which occurs when blood glucose levels exceed the renal threshold for reabsorption in the proximal tubule.

The most likely associated condition is diabetes mellitus.

100

Explain why Na⁺ is considered the major determinant of ECF osmolarity and how this affects water movement.

Na⁺ is the major determinant of ECF osmolarity because it is the most abundant effective osmole in the extracellular fluid and is largely restricted to the ECF due to the Na⁺/K⁺ ATPase maintaining high Na⁺ outside cells.

Because water moves by osmosis toward higher solute concentration, changes in Na⁺ concentration directly change ECF osmolarity and therefore drive water movement between compartments:

  • If ECF Na⁺ increases (high osmolarity) → water moves out of cells into ECF, causing cells to shrink.
  • If ECF Na⁺ decreases (low osmolarity) → water moves into cells, causing cells to swell.

Thus, Na⁺ effectively “controls” ECF osmolarity, and water follows Na⁺ to maintain osmotic balance between ECF and ICF.

100

What is the primary cause of respiratory alkalosis, and how does it change CO₂ levels in the blood?

The primary cause of respiratory alkalosis is hyperventilation (increased breathing rate or depth), which can occur due to anxiety, high altitude, fever, or sepsis.

Hyperventilation causes the lungs to remove CO₂ from the blood faster than it is produced, leading to a decrease in arterial CO₂ (PCO₂). This drop in CO₂ shifts the carbonic acid–bicarbonate equilibrium to the left, reducing H⁺ concentration and increasing blood pH.

200

Define GFR and describe one consequence of a GFR that is too high and one consequence of a GFR that is too low.

GFR (glomerular filtration rate) is the amount of filtrate formed per minute by both kidneys combined. It reflects how well the kidneys are filtering blood.

  • If GFR is too high: Fluid moves through the renal tubules too quickly, so there is insufficient time for reabsorption of water and solutes, which can lead to dehydration and electrolyte loss.
  • If GFR is too low: Fluid moves too slowly through the tubules, allowing excess reabsorption of wastes that should be excreted, which can lead to buildup of toxins in the blood (azotemia/uremia).
200

Name the cotransporter responsible for Na⁺ reabsorption in the thick ascending limb and briefly describe how it works.

The cotransporter in the thick ascending limb is the Na⁺/K⁺/2Cl⁻ cotransporter (NKCC2).

It works by simultaneously moving Na⁺, K⁺, and 2 Cl⁻ ions from the tubular fluid into the epithelial cells of the thick ascending limb. This process is driven by the low intracellular Na⁺ concentration created by the basolateral Na⁺/K⁺ ATPase, which indirectly powers the cotransporter. The thick ascending limb is impermeable to water, so solutes are reabsorbed without water following.

200

Match the odor to the correct condition:

A. Sweet/fruity odor
B. Musty (“mousy”) odor
C. Ammoniacal odor

  1. UTI (urease-producing bacteria)
  2. Phenylketonuria (PKU)
  3. Diabetic ketoacidosis (DKA)

A. Sweet/fruity odor → Diabetic ketoacidosis (DKA)
B. Musty (“mousy”) odor → Phenylketonuria (PKU)
C. Ammoniacal odor → UTI (urease-producing bacteria)

200

Explain why principal cells can either secrete or conserve K⁺ depending on the body’s needs.

Principal cells can either secrete or conserve K⁺ because their transport activity is hormonally and electrochemically regulated depending on the body’s K⁺ balance.

  • When K⁺ levels are high (hyperkalemia), aldosterone is released, which increases Na⁺ reabsorption through ENaC channels and enhances Na⁺/K⁺ ATPase activity. This increases intracellular K⁺ and creates a gradient that promotes K⁺ secretion into the tubular fluid, allowing excess K⁺ to be excreted.
  • When K⁺ levels are low (hypokalemia), aldosterone levels drop and K⁺ secretion decreases. In addition, the driving forces for K⁺ secretion are reduced, so the kidney conserves K⁺, and in some cases K⁺ reabsorption mechanisms become more prominent.

Thus, principal cells adjust K⁺ handling to maintain tight homeostasis of plasma potassium levels, which is critical for normal membrane excitability in muscles and nerves.

200

Give one cause each of:

  • metabolic acidosis
  • metabolic alkalosis


  • Metabolic acidosis: Diabetic ketoacidosis (DKA) (or other acceptable cause: diarrhea, lactic acidosis, kidney failure)
  • Metabolic alkalosis: Vomiting (loss of gastric acid)



300

Explain how the myogenic mechanism prevents damage to the glomerulus during high blood pressure.


The myogenic mechanism protects the glomerulus by responding to increased blood pressure through an intrinsic smooth muscle response in the afferent arteriole.

When blood pressure rises, the afferent arteriole stretches, which opens mechanically gated ion channels in the smooth muscle cells. This leads to Ca²⁺ influx, causing the smooth muscle to contract. The arteriole then vasoconstricts, which reduces blood flow into the glomerulus.

This constriction helps lower glomerular capillary pressure, preventing excessive filtration and protecting the glomerulus from damage while keeping GFR relatively stable.

300

Describe the role of ADH and aldosterone in the late DCT and collecting duct.

In the late distal convoluted tubule (DCT) and collecting duct, both hormones fine-tune fluid and electrolyte balance:

  • ADH (antidiuretic hormone): Increases water permeability by inserting aquaporin channels into the collecting duct, allowing more water to be reabsorbed by osmosis. This concentrates the urine and reduces water loss.
  • Aldosterone: Increases Na⁺ reabsorption (via ENaC channels) and promotes K⁺ secretion in principal cells. Water follows Na⁺ osmotically, so this indirectly increases water reabsorption and helps raise blood volume and blood pressure.
300

List the three layers of the ureter wall and briefly describe the function of each.


The three layers of the ureter wall are:

  1. Mucosa (urothelium + lamina propria)
    • Function: Lines the lumen and provides a stretchable, protective barrier that prevents urine from damaging underlying tissues.
  2. Muscularis
    • Function: Contains smooth muscle that generates peristaltic contractions to propel urine from the kidneys to the bladder.
  3. Adventitia
    • Function: Outermost connective tissue layer that provides support and anchors the ureter, containing blood vessels, nerves, and lymphatics.


300

List the three major physiological responses to dehydration that help restore fluid balance.


The three major physiological responses to dehydration are:

  1. Increased thirst – stimulates water intake via the hypothalamic thirst center.
  2. Increased ADH release – promotes water reabsorption in the collecting ducts, reducing urine output and concentrating urine.
  3. Activation of RAAS (renin-angiotensin-aldosterone system) – increases Na⁺ reabsorption (and water follows), helping restore blood volume and blood pressure.
300

List the normal ranges for:

  • pH
  • PCO₂
  • HCO₃⁻
  • pH: 7.35 – 7.45
  • PCO₂: 35 – 45 mmHg
  • HCO₃⁻: 22 – 26 mEq/L
400

Name the three components of the juxtaglomerular apparatus and give one function of each.

The three components of the juxtaglomerular apparatus (JGA) are:

  1. Macula densa
    • Function: Detects NaCl concentration in the distal convoluted tubule and helps regulate GFR via tubuloglomerular feedback.
  2. Juxtaglomerular (JG) cells
    • Function: Secrete renin in response to low blood pressure, low NaCl, or sympathetic stimulation.
  3. Extraglomerular mesangial cells (lacis cells)
    • Function: Provide structural support and help transmit signals between the macula densa and JG cells.
400

Explain how the loop of Henle creates the medullary osmotic gradient using countercurrent multiplication.

The loop of Henle creates the medullary osmotic gradient through countercurrent multiplication, which depends on opposite fluid flow in its two limbs and different transport properties.

In the thick ascending limb, Na⁺ and Cl⁻ are actively reabsorbed into the medullary interstitium via the NKCC2 cotransporter, but this segment is impermeable to water, so water cannot follow. This makes the surrounding interstitium increasingly hyperosmotic.

In contrast, the descending limb is permeable to water but not solutes, so water leaves the tubule by osmosis into the salty medulla, concentrating the filtrate as it moves downward.

Because fluid flows in opposite directions in the two limbs, this small stepwise difference is continuously “multiplied” along the loop, progressively increasing osmolarity deeper in the medulla. This establishes the corticomedullary gradient, which is essential for concentrating urine.

400

Compare the roles of the sympathetic and parasympathetic nervous systems in bladder control.

The sympathetic nervous system (T11–L2) promotes urine storage. It causes the detrusor muscle to relax (β3 receptors) and the internal urethral sphincter to contract (α1 receptors), allowing the bladder to fill without leaking urine.

The parasympathetic nervous system (S2–S4) promotes urine voiding (micturition). It causes the detrusor muscle to contract (M3 receptors) and the internal urethral sphincter to relax, enabling urine to be expelled from the bladder.

400

A patient has low blood pressure and high plasma osmolarity. Explain how RAAS and ADH work together to restore homeostasis.

With low blood pressure and high plasma osmolarity, the body activates both RAAS and ADH, which work together to restore both volume and osmolarity balance:

  • RAAS activation (triggered by low blood pressure):
    The kidneys release renin → forms angiotensin II → stimulates aldosterone release. Aldosterone increases Na⁺ reabsorption in the distal nephron, and water follows Na⁺, helping to restore blood volume and blood pressure.
  • ADH release (triggered by high plasma osmolarity):
    The hypothalamus stimulates ADH secretion from the posterior pituitary. ADH increases water permeability in the collecting ducts via aquaporins, allowing more free water reabsorption, which helps lower plasma osmolarity and concentrate urine.

RAAS primarily restores blood volume/pressure (Na⁺ + water retention), while ADH primarily corrects osmolarity (water retention without Na⁺), leading to coordinated restoration of homeostasis.

400

Given:

  • pH = 7.30
  • PCO₂ = 50 mmHg
  • HCO₃⁻ = 24 mEq/L

Identify:

  • primary disorder
  • whether compensation is present
  • Primary disorder: Respiratory acidosis (low pH with elevated PCO₂ indicates CO₂ retention from hypoventilation)
  • Compensation: Uncompensated (HCO₃⁻ is still normal, so kidneys have not yet increased bicarbonate)
500

Trace the steps of the RAAS system from decreased blood pressure to angiotensin II formation.

When blood pressure decreases, the RAAS pathway is activated as follows:

  1. Decreased blood pressure (or decreased GFR) is detected by the kidney.
  2. Juxtaglomerular (JG) cells in the afferent arteriole release renin.
  3. Renin converts angiotensinogen (a plasma protein made by the liver) into angiotensin I.
  4. Angiotensin I circulates to the lungs and vascular endothelium.
  5. ACE (angiotensin-converting enzyme) converts angiotensin I into angiotensin II, the active hormone.

➡ Angiotensin II is then responsible for increasing blood pressure and helping restore GFR.

500

Compare obligatory vs facultative water reabsorption, including where each occurs and whether it is hormonally controlled.

Obligatory water reabsorption is the automatic, constant reabsorption of water that occurs regardless of the body’s hydration status. It happens in the proximal convoluted tubule and the descending limb of the loop of Henle, where water follows solute reabsorption by osmosis. It is not hormonally controlled.

Facultative water reabsorption is variable and regulated based on the body’s needs. It occurs mainly in the late distal convoluted tubule and collecting duct and is controlled by ADH, which increases water permeability by inserting aquaporins. This allows the body to adjust urine concentration and conserve water when needed.

500

A patient has difficulty voiding and cannot fully empty the bladder due to loss of parasympathetic function.
Explain how this affects:

  • detrusor muscle activity
  • internal and external urethral sphincters
  • overall urine output and residual volume

Loss of parasympathetic (S2–S4) function disrupts the micturition reflex and impairs bladder emptying:

  • Detrusor muscle activity: The detrusor receives little to no M3 stimulation, so it becomes weak or unable to contract effectively, reducing bladder pressure needed for voiding.
  • Internal and external urethral sphincters: The internal urethral sphincter remains relatively constricted because sympathetic tone is unopposed. The external urethral sphincter (somatic control via pudendal nerve) is still under voluntary control, but urine cannot be effectively expelled without detrusor contraction.
  • Overall urine output and residual volume: The patient has reduced urine voiding efficiency, leading to incomplete bladder emptying and increased residual urine volume, which can cause urinary retention and increased risk of infection.
500

Explain what happens in hypotonic hydration (water intoxication) in terms of:

  • plasma osmolarity
  • cell volume
  • ADH levels

In hypotonic hydration (water intoxication):

  • Plasma osmolarity: Decreases due to excess water diluting solutes (especially Na⁺), leading to hypotonic ECF.
  • Cell volume: Increases because water moves from the dilute ECF into cells by osmosis, causing cells to swell (can lead to cerebral edema).
  • ADH levels: Decreased as the hypothalamus detects low osmolarity, reducing ADH release and promoting water excretion (though this may be overwhelmed if water intake is excessive).
500

Differentiate between:

  • uncompensated
  • partially compensated
  • fully compensated acid–base disorders

(What happens to pH and the other variables?)

  • Uncompensated:
    • pH: abnormal
    • One system (respiratory or metabolic): abnormal (primary problem)
    • Other system: normal (no compensation yet)
  • Partially compensated:
    • pH: abnormal (still not corrected)
    • Both systems: abnormal
      • primary disorder present
      • compensatory system has started adjusting (CO₂ or HCO₃⁻ moving in opposite direction)
  • Fully compensated:
    • pH: back in normal range (7.35–7.45), but may be near a limit
    • Both systems: abnormal
      • primary disorder still present
      • full compensation by the other system has normalized pH
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