Lecture 18 - Renal Pathology 1 Flashcards by Eleanor Nicklason

Give an overview of the structure of the kidney

Two per person
150g each
Renal artery & vein
Ureters
Cortex & medulla
Renal pyramids
Ureteric pelvis

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Kidneys & hormones?

The kidney makes hormones:
• Renin
• Erythropoietin

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What are some general functions of the kidneys?

Excretion of metabolites & waste
Na+ and H20 balance
Maintenance of pH
Hormone production

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What are the ‘four components’ of the kidney?

Glomeruli
Tubules
Interstitium
Blood vessels

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Describe the anatomy of the glomerulus

How many per adult?

Normal adult: 1x10^6

Cluster of specialised capillary loops
Afferent & efferent arteriole
Fenestrated endothelium
Specialised basement membrane

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Describe basic urine formation

Filtration
Water and solutes pass through fenestrated wall into urinary space

2. Reabsorption
 • Occurs along the tubules
 • PCT: bulk reabsorption
 • Loop of Henle: concentration of urine
 • DCT: fine tuning of urine composition
 • Collecting duct: water reabsorption

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What is the metabolic demand of the kidney tubule cells?

Very high demand

* Due to active transport occurring along the tubules

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What is the tubulo-interstitium?

Interstitium + kidney tubules

• The function of these two elements is inseparable

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What is meant by acute renal disease?

Quick onset
Reversible element to abnormalities

NB Some acute renal injury may be reversible

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List the clinical syndromes of renal disease

Acute renal failure
Nephrotic syndrome
Nephritic syndrome
Gross / macroscopic haematuria
Microscopic haematuria
Asymptomatic proteinuria
Chronic renal failure

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What is GFR?

Glomerular filtration rate

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Describe acute renal failure

What is the aetiology?

NB Not a term for general acute renal abnormality!

Acute reduction in Glomerular filtration rate (GFR)
Reflected as reduced creatinine clearance
Increased serum creatinine

3 aetiological groups:

Pre-renal
Renal
Post-renal

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What is ‘pre-renal’ acute renal failure?

Not enough blood getting to the kidney for proper function

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What is ‘renal’ acute renal failure?

What is the most common cause of this?

Problem with the kidney itself

Causes:
Most common:
 • Acute tubular necrosis
also
 • Acute Glomerulonephritis
 • Acute interstitial nephritis
etc.

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What is ‘post-renal’ acute renal failure?

Necessary urinary drainage isn’t happening

```
e.g.
• Ureteric obstruction
calculus in lumen, tumour in wall
• Urethral obstruction
(prostatic enlargement)
~~~

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What is nephrotic syndrome?

• Leaky glomerulus
• Proteins escape into urine
→ Proteinuria

Features:
 • Oedema (whole body)
- due to reduced plasma oncotic pressure
 • Proteinuria
 • Hypoalbuminaemia
 • Hyperlipidaemia

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What are some common causes of proteinuria or nephrotic syndrome?

Diabetes mellitus
Glomerulonephritis
Amyloid deposition (Amyloidosis)

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Describe Acute tubular necrosis

Reversible / irreversible?

Under-perfusion severe and long enough to cause death of tubular epithelial cells
→
 • Necrosis of tubular epithelial cells
 • Dilation of tubules
 • Tubular casts: sloughing into lumen
 • Oedema in interstitium
 • Glomeruli and vessels preserved

• Reversible

Regeneration
• May take weeks

Describe Glomerulonephritis

What are the sequelae?

• Acute injury to the glomerulus
 • Most often immune mediated
 • Deposition of immune complexes in the tuft
→ C' activation
→ Formation of MAC

Rare but important minority due to:
• Direct anti-Glomerular Basement Membrane antibodies

Sequelae:
• Rapid progression w/ crescents
• Reversible
• Slowly progressive to chronic renal failure

What are crescents?

In which disease are they observed?

Observed in Glomerulonephritis

If severe:
• Clumps of monocytes & epithelial cells accumulate in capillary tufts

Composition:
• Cells
• Fibrin
• Clotted blood

Location:
• Outside the glomerular capillary
• In the urinary space

What is a ‘segmental scar’?

A slower, less acutely damaging glomerulonephritis

Describe acute interstitial nephritis

How does it normally present?

Aetiology?

Interstitium and tubules infiltrated by inflammatory cells (eosinophils)

Usually presents as acute renal failure
• +/- blood or protein in urine

Symptoms:
• Fever
• Rash

Aetiology:
• Drug allergy (e.g. antibiotics)

Which cells are often seen in the interstitium in acute interstitial nephritis?

Eosinophils

What are three important causes of acute renal injury?

Acute tubular necrosis
Acute glomerulonephritis
Acute interstitial nephritis

How much cardiac output do the kidneys receive?

20%

Why is it significant that the blood in the glomeruli is drained by an arteriole?

The efferent arteriole can vasodilator or constrict, controlled very finely the pressure. GFR can be very finely controlled

Where is the urinary space?

Inside the Bowman's capsule

What are the mechanisms of control of filtration?

* Foot processes of the podocytes | * Vasodilation & vasoconstriction of the afferent & efferent arterioles to control GFR

What type of cells form the tubules? | What is important about them?

Specialised epithelium | Very high metabolic demand

Where is the basement membrane?

Formed on the outside of the endothelium of the glomerulus

What is mesangium?

= Mesangial cell Function: • Phagocytic • Secrete the amorphous basement membrane-like material known as the mesangial matrix Contained within the basement membrane

Compare acute renal failure and nephrotic syndrome

Acute renal failure: not enough blood perfusing | Nephrotic syndrome: leaky basement membrane

Explain Starlings forces

Plasma osmotic pressure Plasma hydrostatic pressure Interstitial osmotic pressure Interstitial hydrostatic pressure This maintains volume in capillaries The proteins in the blood are the main driver of reabsorption of fluid back into the capillaries

Is filtration active or passive? | What about reabsorption?

Filtration: passive Reabsorption: active

Why do tubular epithelial cells rapidly undergo necrosis

* Highly metabolically active; stuffed with mitochondria | * When ischemic, they rapidly undergo necrosis

Is acute tubular necrosis reversible?

Yes | After a few weeks on dialysis, the tubules will grow back

What is by far the most common cause of acute renal failure?

Acute tubular necrosis

Where are the foot processes of the podocytes?

Wrap around the outside of the glomerular capillaries

What gets triggered when immune complexes are deposited in the glomeruli?

C' activation • Recruitment of inflammatory cells • MAC formation

What is Goodpasture syndrome?

A very rare form of Glomerulonephritis • Caused by antibodies directed against their own basement membrane • 'Anti-Basement membrane' antibodies → C' activation, MAC formation etc. (like in normal GN) There is the same outcome, but extremely rare

Where do crescents form?

In the extra-glomerular space (not in the capillary)

What can trigger acute glomerulonephritis?

Bacterial infection • Streptococcal infection in throat NB Antibiotic use could lead to...*

What is Bright's disease?

Post-streptococcal acute glomerulonephritis