10.3 Pathophysiological Mechanisms Underlying Renal Failure (Part 2)

Question 1

List the triad of haemolytic uraemic syndrome, and explain each component

Answer 1

• Microangiopathic haemolytic anaemia (schistocytes are damaged due to microthrombi, which are then filtered by the reticuloendothelial system)
• Thrombocytopaenia (platelets depleted due to large amounts of clotting in microvasculature)
• AKI (reduced perfusion of the kidney)

Question 2

Give an end-to-end explanation of how certain kinds of E coli can cause HUS

Answer 2

• E coli releases shiga toxin
• Shiga toxin binds to renal endothelium, creating damage that induces a hypercoagulable state
• This leads to microthrombi formation in renal microvasculature, leading to thrombocytopaenia [1] and damaging the erythrocytes that try to flow through
• These damaged RBCs are then filtered out by the reticuloendothelial systems of the liver and spleen (leading to microangiopathic haemolytic anaemia [2])
• This decreased perfusion to the kidney also causes AKI [3]

Question 3

List four environmental toxins that can cause renal damage

Answer 3

• Snake venom
• Heavy metals
• Poison produced by mushrooms
• Certain chemicals (e.g. ethylene glycol)

Question 4

How does goodpastures disease cause renal damage? What is this disease also called?

Answer 4

• Also called anti-GBM glomerulonephritis
• The body develops an intolerance to its own Type-IV collagen, which is present in the glomerular basement membrane and the lungs
• The immune system mounts an antibody-mediated attack on the GBM, leading to acute kidney injury (and haemoptysis, since lungs are also attacked)

Question 5

How does SLE damage the kidneys?

Answer 5

• In Lupus, widespread autoantibody-mediated tissue damage occurs
• These immune complexes can then deposit in glomeruli, leading to activation of the complement, localised inflammatory immune response, and thus damage to the kidneys in a condition known as lupus nephritis

Question 6

What is preeclampsia? How does it damage the kidneys?

Answer 6

• Preeclampsia is a state of elevated blood pressure during pregnancy - it is proposed this occurs in response to reduced placental blood flow, such as in abnormal modelling of the placental vasculature
• This leads to widespread endothelial dysfunction (presumably in response to hypoxic factors made by the placenta) as well as inflammation, increasing the permeability of the glomerulus, and disrupting regular filtration

This is why proteinuria is a key sign of preeclampsia.

Question 7

How can multiple myeloma cause kidney damage?

Answer 7

• Malignant clones of plasma cells pump out large quantities of light chains
• These soon saturate the reabsorptive capacity of the kidneys, depositing in the tubules (where they have toxic effect) and forming casts that can be seen on urine microscopy

Question 8

What can cause rhabdomolysis? How can rhabdomyolysis cause kidney damage? What biomarker do we use to detect rhabdo?

Answer 8

• Common cause is statins; can also be caused by snake venom and heatstroke
• Myoglobin released during muscle lysis crosses the GBM, where it can cause damage to the renal tubules
• Elevated creatine kinase (usually contained in muscle cells) is a common biomarker used to detect rhabdomyolysis

Question 9

How can haemolysis damage the kidneys?

Answer 9

• Haemolysis increases the amount of free haemoglobin in the blood
• This is filtered in the kidneys, and the haem-iron induces oxidative stress that damages the kidney. Plus, the haem can form casts that reduce the ability of the tubules to operate.

Question 10

How does renal artery stenosis damage the kidneys? What are two possible causes of it (w/ specific name)?

Answer 10

Cause 1: atherosclerosis narrows the renal arteries
Cause 2: Fibromuscular dysplasisa (abnormal growth of cells in the arterial wall)

Leads to less blood going through kidneys, causing RAAS overactivation as lower BP is detected by JG cells.

Question 11

True or false: JG cells are baroreceptive

Answer 11

• True
• This is very important

Question 12

Explain two overarching mechanisms by which drugs can damage the kidneys

Answer 12

1. They are inherently nephrotoxic (e.g. gentamicin)
2. They are renally cleared, and in the context of low GFR, accumulate, which leads to toxicity

Question 13

What is the name of an immune-mediated disorder that causes kidney inflammation, usually drug-induced?

Answer 13

Acute interstitial nephritis (AIN; pAINful)

Question 14

What are some common kinds of nephrotoxic drugs (either via accumulation or inherent toxicity)?

Answer 14

• Aminoglycosides (-mycin), when accumulated
• NSAIDs (why?)
• Contrast dye (inherently nephrotoxic)