lecture 18

Question 1

What are the kidneys?

Answer 1

• usually two, about 150 gm each in the adult
• hide behind the ribs on the back
• each supplied by an artery, and drained by a vein and a tube to the bladder on each each side: a ureter
• the urine is a concentrated aqueous solution that allows us to:
• • excrete various metabolites and toxins
• • maintain appropriate water and sodium balance
• • maintain appropriate pH
• the kidney also makes some essential hormones including renin and erythropoietin

Question 2

What are four basic histological components of the kidneys?

Answer 2

• glomeruli (everyone recognises)
• tubules
• interstitium (the bit everyone forgets)
• blood vessels

Question 3

What is the glomerulus?

Answer 3

• number varies but often given as roughly 1 x 10^6 per kidney in the adult
• comprises a cluster of specialised capillary loops with an arteriole that brings blood in (afferent) and an arteriole that drains blood out (efferent), and:
• • specialised basement membrane forming the wall of the capillary lining of endothelium with large pores (‘fenestrated endothelium’)
• • covering on the urinary surface of specialised epithelial cells that are continuous with the epithelium lining the tubules
• because it is both supplied and drained by an artery it means that we can easily control the pressure of the blood being filtered by the kidney
• exquisite control of intraluminal pressure

Question 4

What is the basic sequence of events in the glomerulus/nephron?

Answer 4

1. water and solutes pass through wall into urinary space: red cells and most proteins stay behind: physical and electrical aspects of wall are important. Passive.
2. complex reabsorption then occurs along the tubule, regulating the body’s balance of water, sodium, potassium and other molecules: some not reabsorbed and are excreted

what we pee out should ideally not have blood cells in it, proteins, just as much as water as we need to excrete, sodium and bicarbonate

Question 5

What are the tubules?

Answer 5

• structure and function vary along the length of the tubule
• lined by specialised epithelial cells with high metabolic demand
• function is inseparable from interstitium (in fact the two are often described together as the ‘tubulo-interstitium’)

Question 6

What are the basics of renal disease?

Answer 6

• ‘acute’ relates to time course: it describes something that happens quickly
• in renal disease there is an extra connotation in the name – it often means there is a reversible element to the abnormalities, though some acute renal injury may be irreversible
• chronic injury tends to be associated with fibrosis and currently is usually irreversible
• recognised historically that people with renal pathology present with very different clinical problems, depending on the particular aspect of renal function that is affected
• the names for these syndromes are old but still used

Question 7

What is a clinical presentation?

Answer 7

• several different ways people present if some aspect of their kidney function is noted to be changing quickly

Question 8

What are clinical renal syndromes?

Answer 8

• acute renal failure
• nephrotic syndrome
• nephritic syndrome
• gross/macroscopic haematuria
• microscopic haematuria
• asymptomatic proteinuria
• chronic renal failure

Question 9

What is acute renal failure?

Answer 9

• unfortunately sounds like a general term for any acute renal abnormality – it isn’t
• it specifically refers to an acute reduction in glomerular filtration rate (GFR) reflected as reduced creatinine clearance – result is increasing serum creatinine
• often broken into 3 aetiological groups
• • pre renal
• • renal
• • post renal

Question 10

What is the aetiology of acute renal failure?

Answer 10

Pre-renal (not enough blood getting to kidney for it to do its job):

• dehydration
• shock/circulatory collapse

Renal (a problem with the machinery itself):

• acute tubular necrosis
• acute cortical necrosis
• acute glomerulonephritis
• interstitial nephritis
• papillary necrosis

post renal (necessary urinary drainage isn’t happening)

• ureteric obstruction due to
• • something in the lumen such as calculus or tumour or clot
• • something in the wall such as tumour
• • something external compressing the ureter
• urethral obstruction due to
• • prostatic enlargement
• etc.

Question 11

What is nephrotic syndrome?

Answer 11

1. oedema, typically affecting the whole body
2. proteinuria (generally more than 3 or 4 g/day)
3. hypoalbuminaemia
4. hyperlididaemia

• basic defect is that the sieve leaks: the permeability of the capillary walls is wrong and proteins (particularly albumin) escape into the urine
• the other components of the syndrome follow on from the proteinuria

1. glomerulus leaks protein
2. proteinuria
3. body can’t keep up production so hypoproteinaemia
4. low protein means reduced osmotic gradient to retain water within microcirculation
5. water accumulates in extra-capillary compartments
6. oedema

Question 12

What are common causes of proteinuria or nephrotic syndrome?

Answer 12

• diabetes mellitus
• some forms of glomerulonephritis
• • minimal change disease
• • membranous glomerulonephritis
• amyloid deposition
• normal function = absence of acute renal failure (i.e. sodium etc normal) but can still have +++ protein

Question 13

What is the relationship between the pathology and the clinical presentation?

Answer 13

• distinguish between these clinical syndromes (words that describe the clinical presentations of illness) and the pathological processes
• the type of pathology and the clinical presentation may not map directly to each other, so a particular syndrome (e.g. nephrotic syndrome) may be due to any of the several different pathological processes (e.g. diabetic nephropathy, forms of glomerulonephritis, amyloidosis etc.)

Question 14

What is the importance of microscopy?

Answer 14

• coming at renal disease from the other direction: pathological processes rather than the clinical presentation
• these are critical and often the pathologist is the one who makes the diagnosis, on the basis of microscopy
• in real life the clinical presentation and history, the biochemical findings in blood and urine, perhaps serology and so on are all very important and the microscopy alone may be just one part of the puzzle

Question 15

What is the pathology of acute tubular necrosis?

Answer 15

• necrosis of tubular epithelial cells with sloughing into lumen (tubular casts) and oedema in interstitium
• reversible lesion
• regeneration and complete recovery may take weeks
• this is by far the commonest renal cause of Acute Renal Failure
• almost always caused by ischaemia: cells in the tubule are very metabolically active –> need oxygen and so on to function properly

Question 16

What is hypoperfusion?

Answer 16

• hypoperfusion as a pre-renal cause is not the same thing as Acute Tubular necrosis in the ‘renal’ causes
• • both are associated with not enough blood perfusing the kidney but…
• • acute tubular necrosis means the under-perfusion was severe enough and long enough to cause death of tubular epithelial cells

Question 17

What happens in acute tubular necrosis following severe hypotension?

Answer 17

• tubular epithelial cells die
• tubules dilate
• sloughed epithelial cells lies in lumen
• tubular function impaired
• other components (glomeruli, vessels, interstitium) preserved

Question 18

What is the pathology of glomerulonephritis?

Answer 18

• acute injury to glomerulus, most often immune mediated
• many (but not all) are associated with deposition of immune complexes in the tuft (followed by complement activation, formation of membrane attack complex etc.)
• rare BUT IMPORTANT minority due to direct anti-Glomerular Basement Membrane antibodies
• clinical consequences depend on what forms the complexes, where they lodge, how big they are

Question 19

What is acute glomerulonephritis?

Answer 19

• may be acute, reversible injury
• may be rapidbly progressive with crescents
• may be slowly progressive to chronic renal failure
• if severe and associated with necrosis of part of the capillary tuft, acute GN may be associated with clumps of monocytes and epithelial cells, called ‘crescents’
• e.g. IgA nephropathy

immune-mediated injury 95% caused by lodging of immune complexes
if severe enough part of the glomerulus just dies

Question 20

What is a crescent?

Answer 20

• in glomerulonephritis
• if severe enough part of the glomerulus will die
• clotted fibrin, inflammatory cells, nuclear debris and blood –> crescent
• cellular: recruited monocytes and epithelial cells
• crescent is not in the capillary it is in the extraglomerular space/urinary space

Question 21

What happens in indolent forms of glomerulonephritis?

Answer 21

• segmental scar

- less acutely damaging

Question 22

How is electron microscopy useful in glomerulonephritis?

Answer 22

• can reveal the location of immune complexes

- different locations will cause different diseases

Question 23

What is acute interstitial nephritis?

Answer 23

• usually presents as acute renal failure, sometimes with some blood protein in the urine
• interstitium and tubules infiltrated by inflammatory cells, often with many eosinophils
• often fever, maybe a rash
• very often due to drug allergy (e.g. antibiotics)