Glomerular pathology

Question 1

What is nephrotic syndrome?

Answer 1

loss of protein through the glomerulus into urine

Question 2

What is nephritic syndrome?

Answer 2

loss of blood into urine w/ renal failure and hypertension, you usually get protein loss with it

Question 3

What is the site of injury in nephrotic syndromes?

Answer 3

the podocytes/ subepithelium or basement membrane

Question 4

What is the site of injury in nephritic syndromes?

Answer 4

the endothelium of the glomerulus

Question 5

Why can lupus cause either nephritic or nephrotic syndrome?

Answer 5

because the autoantibodies can attack the endothelium, GBM or podocytes, and the location of damage determines the type

Question 6

Give the 4 commonest primary causes of nephrotic syndrome

Answer 6

• minimal change nephritis
• focal segmental glomerular sclerosis (FSGS)
• Membranous glomerular nephritis
• lupus

Question 7

Give two secondary causes of nephrotic syndrome

Answer 7

• diabetes
• hypertension
• amyloidosis

Question 8

What are the signs and symptoms of a nephrotic syndrome?

Answer 8

• odema, particularly in the face in children and legs in adults
• frothiness of urine due to prescence of protein
• infections, lethargy, fatigue
• hypercoagulabilty (may present as DVT)
• Xanthelasma
• breathlessness (due to pleural effusion)

Question 9

Why do ppl with nephrotic syndrome get hyper-coagulability and xanthelasma?

Answer 9

Albumin levels drop as its being excreted in urine, so liver works harder to replace it, a side effect of this however is increased lipid production (xanthelasma) and increased clotting factor production

Question 10

What is the commonest cause is nephrotic syndrome in children?

Answer 10

Minimal change nephritis

Question 11

What causes minimal change nephritis?

Answer 11

they dont know, there is no evidence of immune complex deposition of anything

Question 12

How is minimal change nephritis managed?

Answer 12

• biopsy + need TEM to see podocyte damage (no pathology can be seen under a light microscope)
• give steroids to put them into remission
• doesnt often progress to renal failure

Question 13

What is the pathophysiology to focal segmental glomerular sclerosis?

Answer 13

Something (they dont know what) causes scarring of sections of glomerulus

Question 14

Do transplants or steroids work to treat FSGS?

Answer 14

Steroids have some benefit.
The transplants also get FSGS so dont really help.
Most progress to renal failure as scarring eventually leads to drop in GFR

Question 15

What is the classic triad of findings seen in nephrotic syndrome

Answer 15

• Protein urea of >3.5 g/day
• Low blood albumin
• Odema and high lipids

Question 16

What is the pathophyiology do membranous glomerularnephritis

Answer 16

Damage to the basement membrane as a result of IgG forming immune complexes with an antigen on the basement membrane/ podocytes (autoimmune).
It may be secondary to other diseases for example its been associated with lymphoma

Question 17

Describe how diebetes starts to cause nephropathy and why the early signs are kidney hypertrophy and increased GFR

Answer 17

• Glycation damages the microvascular structures such as the afferent arteriole to thicken (hyaline sclerosis). This increases glomerular pressure and increases GFR.
• More glucose in nephron means more Na+ reabsorbtion in PCT, so less goes to DCT and this activates RAAS leading to hypertension
• The mesangeal cells secrete more matrix and so cause more hypertrophy
• The increased GFR which leads to kidney hypertrophy

Question 18

What are kimmelsteil wilson nodules?

Answer 18

Nodules made by mesangeal cells secreteing more matrix as a result of diabetic nephropathy

Question 19

Why do microalbuminurea start to occur after latent diabetic nephropathy?

Answer 19

The mesangeal cells secreting more matrix thickens the basement membrane and leads to podocytes being more spaced out, so the glomerulus is more permeable and so albumin starts to be filtered. At this stage GFR is still normal but small quantities of albumin can be detected by albustix (extrasensitive dipsticks)

Question 20

What happens to GFR when macroalbuminurea sets in?

Answer 20

Eventually mesangeal expansion will impinge on filtration, until GFR drops and lots of albumin is filtered out.

Question 21

What are the risk factors for someone with diabetes to develop end stage renal disease?

Answer 21

• poor control of blood glucose and blood pressure
• genetics
• increasing age
• duration of diabetes (takes yrs to set in)
• smoking

Question 22

How can diabetic nephropathy be treated?

Answer 22

• can be slowed but not stopped
• tight control of diabetes to try make sure youre not hypeglycaemic for too long
• tight control of blood pressure particularly with ACEi and angiotensin blockers because this stops vasoconstriction of the afferent arteriole

Question 23

What are the 6 major primary causes of nephritic syndrome

Answer 23

• IgA nephropathy
• anti GBM
• ANCA vasculitis
• lupus
• thin GBM (may be secondary to alport syndrome)
• post infections

Question 24

What are the signs and symptoms of nephritic syndrome?

Answer 24

haemtauria 
hypertension 
low GFR (causes hypertension)
fatigue 
frothy urine

Question 25

What classical finding is seen on microscopy of a kidney with nephritic syndrome?

Answer 25

red cell clasts (they form in nephrons due to glomerular damage)

Question 26

What age does IgA nephropathy most commonly present?

Answer 26

any age

Question 27

Describe the pathogenesis of IgA nephropathy

Answer 27

IgA- antigen complexes travel from blood and desposit in the mesangium, this damages the endothelium and causes blood to leak out and filter into the nephron. It is often precipitated by mucosal infections which would increase circulating IgA levels.

Question 28

What is the outcome for IgA nephropathy?

Answer 28

some progress to renal failure but some run a benign course

Question 29

What is benign familial nephropathy?

Answer 29

Same as thin GBM nephropathy, basically just that you have a gentically thin GBM, so blood and protein can leak into urine. It is often never noticed unless they get a urine dipstick as its almost always invisible haematuria.

Question 30

What is the defect in alport syndrome? why does this cause nephropathy?

Answer 30

X linked recessive defect in T4 collagen. | Means thin GBM, often progresses to renal failure due to mesangeal expansion, hypertrophy and the resulting drop in GFR

Question 31

What is goodpasture syndrome?

Answer 31

A rare autoimmune attack of the T4 collagen in the GBM, it will rapidly progress to renal failure. It is also called anti GBM

Question 32

How is goodpasture syndrome/ anti GBM treated?

Answer 32

Need urgent referral and immunosurpressants as it can be reversed if caught early but if not it will rapidly progress to renal failure

Question 33

What is ANCA vasculitis and how does it causes nephropathy?

Answer 33

A systemic disorder causing inflammation of the blood vessels, thought to be due to anti neutrophil cytoplasmic antibody (ANCA) release, which causes neutrophils to attack blood vessels of the glomerulus, leading to segmental necrosis of some glomeruli.

Question 34

What other location in the body is commonly affected and systemic symptoms are seen in ANCA vasculitis?

Answer 34

Arterioles in the lungs are also affected. | Systemic symptoms inc: fatigue, arthralgia, myalgia and weight loss

Question 35

How are nephritic and nephrotic syndromes treated generally? (5)

Answer 35

- Treat any odema w/ diuretics and fluid restriction - ACEi to drop BP - Treat underlying conditions- generally by immunosurpression - Statins to lower cholesterol in nephrotic - Manage CVD risks in nephritic

Question 36

Describe how hypertension can cause glomerular nephropathy

Answer 36

1. fibroelastic intima thickens and so the lumen narrows 2. hylanosis of afferent arteriole walls-> drop in GFR 3. these vascular changes lead to ischaemia of glomerulus-> causes glomerular sclerosis 4. sclerosis will cause protein to leak into the nephron 5. when GFR drops, raas is activated, BP increases and hypertension gets worse, leading to a negative cycle

Question 37

State 4 features of hypertensive glomerular sclerosis

Answer 37

- History of poorly controlled hypertension - Recent drop in GFR, proteinuria, heamaturia if very bad - slowly progressive - tiredness, headache, nausia and vomiting may be present if GFR very low - Theyll tend to get hypertensive eye disease and LV hypertrophy before it affects the kidneys

Question 38

How can renal artery stenosis be differentiated from hypertensive renal disease causing GN?

Answer 38

- Hypertension is acute (caused by the renal artery stenosis) - Decline in GFR is more rapid - Often evidence of atherosclerosis elsewhere - Treatment with ACEi will make renal function worse as less compensatory EA constriction so GFR decreases

Question 39

How is hypertensive renal disease managed?

Answer 39

Good control of BP- this will slow progression of the disease

Question 40

How can acute hypertension cause AKI?

Answer 40

An acute large increase in BP can damage kidney vessel endothelium, which can cause ischaemia and necrosis, leading to haematuria and proteinurea as well as a drop in GFR.