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Flashcards in Glomerulonephritis Deck (39):
1

What is glomerulonephritis?

Inflammatory diseases involving the glomerulus and tubules of the kidney
May be primary or secondary

2

What are the mesangial cells of the kidney?

Modified smooth muscle cells.
Capable of contraction to regulate the blood flow and decrease the surface area of the basement membrane (decrease GFR)
Produce the mesangial matrix for structural support of the capillaries in the glomerulus

3

Describe what structures filtrate have to pass through to get from the blood into the tubules.

Fenestrated capillary membrane (endothelium)
Glomerular basement membrane
Podocyte (epithelial cell)

4

What are the two categories of pathological mechanisms that can cause glomerulonephritis?

Extrinsic mechanisms
Intrinsic mechanisms

5

By what extrinsic mechanisms can glomerulonephritis be caused?

Antibodies
- bind to mesangial cells and cause them to release cytokines and GFs
Immune complexes
Complement
Cytokines
Lymphocytes
Other infiltrating cells

6

By which intrinsic mechanisms can glomerulonephritis be caused?

Cytokines
Growth Factors
e.g. TGF-beta, PDGF, interferon-gamma
Vasoactive factors
Proteinuria

7

What part of the kidney can be a possible target for injury?

Mesangial cells
Basement membrane
Epithelial cells
Endothelial cells
Vasculature
Tubular structures
Integrity of glomerulus and tubules

8

Why can end-stage kidney failure happen even when the primary insult is removed?

Hyperfiltration theory
- some of the kidney is destroyed
- parts of the kidney that are left are overworked to try and take over the work of the dead cells
- eventually are exhausted and die as well
- end-stage kidney failure

9

Name some predictors of whether an acute insult may lead to ESKF.

Hypertension - glomerular and systemic
Baseline GFR, serum creatinine
Biopsy - extent of glomerulosclerosis
Biopsy - extent of tubular loss/interstitial fibrosis (relates to glomerular damage)
Age
Primary disease

10

How is glomerulonephritis treated?

Control the precipitating factor
Remove Ab/IC and block Abs
Suppress the response to injury
- steroids
- cytotoxics (cyclophosphamide)
- block matrix
- anti-hypertensives
Manage ESRF
- treatment to slow fibrosis
- dialysis
- transplant
- slow progression

11

Name some of the clinical syndromes/presentations of glomerulonephritis.

Proteinuria
Hypertension
Haematuria
Renal impairment
- reduced GFR (increased serum creatinine)
Nephrotic syndrome
- proteinuria
- decreased serum albumin
- oedema
- hyperlipidaemia ( as liver trues to correct the albumin)
Nephritic syndrome
- hypertension
- haematuria
- oligouria
Rapidly progressing glomerulonephritis
- due to vasculitis
- normal to end stage within 6 weeks

12

Name some histological features of ESKF.

Rapid proliferation
- lots of cells
- increased mitotic index
Glomerulosclerosis

13

What are crenated RBCs?

RBCs that have become crenated by hyper-concentrated urine (glomerular destruction)
Look like WBCs on microscopy

14

What is a RBC cast?

A tube shaped aggregation of RBCs
- a sign of bleeding in the kidney
- a sign of aggressive glomerulonephritis
(Renal tubular epithelial casts indicate severe renal tubular necrosis)

15

What are the main types of glomerulonephritis that you need to know?

Post-infectious GN
IgA nephropathy (most common)
Membranous GB change disease (most common cause of nephrotic syndrome in children)
RPGN/Crescentic GN/Vasculitis
Diabetic nephropathy

16

Describe the progression of post-infectious glomerulonephritis to ESRF.

Infected (streptococci) and Ab/IC produced
Deposition of Ab/IC in the mesangium
Complement activated (hypocomplementaemia) and leukocytes infiltrate
This causes glomerular cell destruction and proliferation of epithelial cells (crescent formation)
Eventually this leads to glomerulosclerosis, tubular loss and hypertensive damage

17

What are the clinical features of post-infectious glomerulonephritis?

Haematuria
Proteinuria
Oedema
Hypertension
Renal impairment
RPGN
Urinary RBC casts

18

What would you expect to see on biopsy if someone has post-infectious glomerulonephritis?

Proliferation of all glomerular cells
Infiltrating lymphocytes

19

How is post-infectious glomerulonephritis treated?

Antibiotics
- penicillin if strep
- broad spectrum for other causes
Dialysis - if it doesn't resolve after a few weeks (most cases)

20

Describe the progression of IgA nephropathy from normal to ESRF.

(Infection?) - production of IgA
- deposited in the mesangium
Lysis of mesangium
Proliferation of mesangium cells
- matrix produced
- healing or scarring occurs
Glomerulosclerosis
Tubular loss
Hypertensive damage

21

How is IgA in IgA nephropathy produced?

Precipitated by infection
- abnormal IgA is produced by the Peyer's patches

22

What diseases can IgA nephropathy be secondary to?

Henoch-Schönlein purpura
Cirrhosis
Coeliac disease

23

What does IgA nephropathy present with?

Haematuria
Hypertension
Proteinuria

24

How is IgA nephropathy treated?

Antihypertensives
- decrease proteinuria
ACE inhibitors

25

Name some of the possible causes of membranous glomerulonephritis.

Tumour
Drugs - gold and penicillin
Hepatitis B and C
Connective Tissue Disease
Idiopathic - 90%

26

Describe the progression of membranous glomerulonephritis from normal to ESRF.

Production of immune complexes and antibodies
- IC deposited in the GBM and mesangium
Alters the GBM charge, and permeability (proteinuria)
Thickened GBM
Glomerulosclerosis
Tubular loss
Hypertensive damage

27

What are the clinical features of membranous glomerulonephritis?

Proteinuria
Nephrotic syndrome
- proteinuria
- decreased albumin
- oedema
- hyperlipidaemia
Hypertension
Renal impairment

28

What is the outcome of membranous glomerulonephritis?

Third - remit
Third - progress to ESRF over 1-2 years
Third - persistent proteinuria, but maintained GFR

29

Describe the specific and non-specific therapies for membranous glomerulonephritis.

Non-specific
- frusemide (oedema)
- ACE inhibitors (hypertension)
- antihypertensive therapy
- NSAIDs
- statins
Specific therapy
- high dose steroids (prednisolone) and chlorambucil (for prevention of B/plasma cell proliferation and antibody production)
Cyclophosphamide/Azathioprine
RITUXIMAB (anti-CD20)
Underling disease

30

What are rapidly progressing glomerulonephritises?

A group of conditions linked by natural history and histology
- crescents on biopsy
- progression to ESRF after a few weeks

31

Name some causes of RPGN.

Good pastures syndrome
- Ab against basement membrane (lungs and kidneys)
Polyarteritis nodosa
- vasculitis of the small blood vessels
Wegeners granulomatosis - midline granulomas (nose, lungs and kidneys)
Post-infectious/bacterial endocarditis
Lupus
Idiopathic

32

What are the symptoms of Wegener's granulomatosis?

Nasal symptoms
- bleeding, stuffiness and deafness
Pulmonary symptoms
- opacities and haemorrhage
Kidney symptoms
- nephrotic/nephritic symptoms
Systemic features

33

What are the biochemical/histological features of Wegener's granulomatosis?

Urinary RBC casts
Anti-neutrophil cytoplasmic antibodies (ANCA)
Crescent around the glomerular capillaries

34

What is the treatment for Wegener's granulomatosis?

Steriods
Cytotoxics
Septrin - prevents antibody production
Transplant

35

What is the pathophysiology of minimal change disease?

T-cell and cytokine mediated
Targets the glomerular epithelial cells, and changes the GBM charge
Glomerular filtration barrier is affected
- proteinuria

36

How can minimal change disease be diagnosed?

Light microscopy
- normal
Electron microscopy
- foot process fusion
Immunoflourescence
- C3 (high due to active disease state)
- IgM depsosition

37

What are the clinical signs of minimal change disease?

Acute - following URTI
GFR - normal or reduced due to intravascular depletion
Renal failure
- oedema decreases circulating blood volume and drops GFR
Nephrotic syndrome
- proteinuria
- decreased albumin
- hyperlipidaemia
- oedema

38

What is the treatment for minimal change disease?

High dose steriods
- prednisolone 40-60mg for 8 weeks
THEN
Cyclosphosphamide if they have multiple relapses
THEN
Cyclosporine (targets T-cells)

39

What do you test on a glomerulonephritis screen and why?

U&Es - excretory functions
LFTs
Glucose - diabetic nephropathy
CRP
FBC - increased WCC in infection
ESR
Urinalysis and microscopy
- blood and protein
Urine protein PCR
Antibodies: ANF (lupus), RF (CTD), anti-GBM and ANCA (vasculitis)
Complement (decreased in RPGN and lupus)
Immunoglobulins A, M, G and electrophoresis (myeloma)
Coagulation (to see if they can have a biopsy)
Hep B, C
HIV
Blood and other cultures