renal 4

Question 1

Q2: Explain the mechanism by which myoglobin damages the kidney.

Answer 1

A:

Myoglobin contains iron, which is redox-active.

In the extracellular space, iron transitions from ferrous (Fe²⁺) to ferric (Fe³⁺) form.

Ferric myoglobin induces oxidative stress, damaging renal tubular epithelial cells.

Precipitates with Tamm–Horsfall protein → forms casts, obstructing nephrons.

Leads to reduced glomerular filtration rate (GFR) and tubular necrosis​​.

Question 2

Q1: Define rhabdomyolysis. What are its main biochemical consequences?

Answer 2

A:
Rhabdomyolysis is the breakdown of skeletal muscle fibers, leading to the release of intracellular contents, especially myoglobin, into the bloodstream.
Key consequences:

Myoglobinuria (dark, rust-colored urine)

Elevated potassium, calcium, sodium, and BUN (blood urea nitrogen)

Risk of cardiac arrest due to hyperkalemia

Can lead to acute kidney injury (AKI)​​.

Question 3

Q3: What histological changes are seen in kidneys affected by rhabdomyolysis?

Answer 3

A:

Shrunken glomeruli with dense capillaries (due to vasoconstriction)

Tubular casts: Pink eosinophilic material (myoglobin + Tamm–Horsfall protein)

Tubular epithelial necrosis: Loss of brush border, detachment from membrane

Brown staining with anti-myoglobin antibody confirms myoglobin presence​.

Question 4

Q4: Describe the role of haptoglobin in rhabdomyolysis.

Answer 4

A:

Haptoglobin binds free heme proteins (e.g. myoglobin, hemoglobin).

This binding neutralizes redox activity and facilitates renal clearance.

Limits oxidative damage and acts as a first-line defense in the bloodstream​​.

Question 5

Q5: What secondary pathway is activated during rhabdomyolysis and how does it contribute to kidney injury?

Answer 5

A:

The renin–angiotensin–aldosterone system (RAAS) is activated.

Myoglobin stimulates renin release, increasing angiotensin II production.

Angiotensin II causes:

Vasoconstriction

Decreased renal perfusion

Increased blood pressure
→ All of which worsen renal damage and reduce GFR​​.

Question 6

Q6: List common causes of rhabdomyolysis.

Answer 6

A:
Physical causes:

Trauma, crush injuries, burns, electrical injuries, prolonged immobility

Extreme exercise, seizures, heatstroke

Non-physical causes:

Drugs (statins, cocaine, amphetamines)

Infections (HIV, influenza, malaria)

Electrolyte imbalances (hypokalemia, hypernatremia)

Endocrine disorders (hypothyroidism)​.

Question 7

Q7: What is the clinical significance of myoglobin’s redox cycling?

Answer 7

A:

Ferric myoglobin (Fe³⁺) can undergo redox cycling, generating reactive oxygen species (ROS).

These ROS damage proteins and lipids, particularly in renal tubular cells.

Contributes to cell death, inflammation, and loss of renal function​.

Question 8

Q8: How do myoglobin-induced casts lead to kidney failure?

Answer 8

A:

Myoglobin + Tamm–Horsfall protein = insoluble casts

Obstruct tubular flow → reduce urine output

Tubular damage + obstruction leads to acute kidney injury and potential anuria​​.

Question 9

Q9: Why might ACE inhibitors be used in rhabdomyolysis-induced AKI?

Answer 9

A:

ACE inhibitors reduce angiotensin II levels.

↓ Ang II → ↓ vasoconstriction → ↑ renal perfusion

Used to mitigate secondary hypertension and help preserve kidney function​.

Question 10

Q10: What is the histological difference between normal and rhabdomyolysis-affected muscle?

Answer 10

A:

Normal muscle: Long, striated fibers with intact nuclei

Damaged muscle:

Lytic cells (loss of intracellular contents)

Pyknosis (condensed nuclei)

Cellular infiltrates (RBCs, immune cells)​​.