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Flashcards in Glomerulonephritis Deck (45)
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1

Definition

Glomerular injury, most often, not always inflammatory in nature. May involve all or part of glomerular apparatus.

2

Commonest causes of end stage renal

1. Diabetes
2. Hypertension
3. GN

3

Etiology (8)

1. Infections (group A beta-haemolytic Streptococcus, respiratory and GI infections, hepatitis B and C, endocarditis, HIV, toxaemia, syphilis, schistosomiasis, malaria, and leprosy)

2. Systemic inflammatory conditions such as vasculitides (SLE, rheumatoid arthritis, and antiglomerulobasement disease, Wegener's granulomatosis, microscopic polyarteritis nodosa, cryoglobulinaemia, Henoch-Schonlein purpura, scleroderma, and haemolytic uraemic syndrome)

3. Drugs (penicillamine, gold sodium thiomalate, NSAIDs, captopril, heroin, mitomycin C, and ciclosporin)

4. Metabolic disorders (diabetes mellitus, hypertension, thyroiditis)

5. Malignancy (lung and colorectal cancer, melanoma, and Hodgkin's lymphoma)

6. Hereditary disorders (Fabry's disease, Alport's syndrome, thin basement membrane disease, and nail-patella syndrome)

7. Deposition diseases (amyloidosis and light chain deposition disease).

8. Idiopathic

4

Primary GN->causes

Primary disease: the pathological glomerular injury is limited to the kidney and not part of a systemic disease manifestation. The injury may or may not be idiopathic. Any systemic symptoms are a result of renal injury.
Post-infectious GN
IgA nephropathy
Anti-glomerular basement membrane (anti-GBM) GN
Idiopathic crescentic GN
Focal segmental glomerulsclerosis
Rapidly progressive.

5

Secondary disease->causes

Secondary disease: renal pathology in this group is a result of systemic disease such as vasculitis, which also has other organ involvement.

SLE
Henoch-Schonlein purpura
Wegener's granulomatosis
Microscopic polyangiitis
Cryoglobulinaemia
Thrombotic microangiopathies
Deposition diseases (amyloidosis, light chain deposition disease)
Malignancies (Hodgkin's lymphoma, lung and colorectal cancer).

6

Nephrotic diseases

Nephrotic syndrome (nephrotic-range proteinuria, hypoalbuminaemia, hyperlipidaemia, and oedema)

Deposition diseases
Minimal change disease (number 1 cause in children)
Focal and segmental glomerulosclerosis (second most common cause in children)
Membranous nephropathy
Membranoproliferative GN.

7

Neprhitic diseases

Nephritic syndrome (haematuria, sub-nephrotic-range proteinuria, and HTN)

IgA nephropathy
Postinfectious GN
Rapidly progressive GN
Vasculitis
Anti-GBM GN.

8

Risk factors

Strong

group A beta-haemolytic Streptococcus
respiratory infections
GI infections
hepatitis B
hepatitis C
infective endocarditis
HIV
SLE
systemic vasculitis
Hodgkin's lymphoma
lung cancer
colorectal cancer
non-Hodgkin's lymphoma
leukaemia
thymoma
haemolytic uraemic syndrome
drugs

9

Clinical presentation

haematuria (common)
oedema (common)
hypertension (common)
oliguria (common)
anorexia (common)
nausea (common)
malaise (common)
weight loss (common)
fever (common)
skin rash (common)
arthralgia (common)
haemoptysis (common)
abdominal pain (common)
sore throat (common)

10

First investigations and interpretations

FBE->normocytic, normochronic
UEC-> +Cr
LFTs->may be + if cause hepatitis/HIV/medications
Albumin->low in nephrotic
24 urine protein
Lipids->hyperlipidemia in neprhotic
Kidney USS may be warranted in some instances

11

Management in mild

May need salt and water restriction
Daily weight
Monitor BP, fluid input and output
Phenoxymethylpenicillin
Regular paracetamol if in pain

12

Management in moderate

moderate-severe disease
Salt/water restriction
Monitor BP
ACE inhibitors and/or angiotensin-II receptor antagonists
Phenoxymethylpenicillin
Furosemide
-->with nephrotic syndrome= prednisolone

13

Management with anti-GBM

Methylprednisilone
Cyclophosphamide
Electrophoresis
Phenoxymethylpenicillin

14

Management with immune complex

Methylprednisilone
Cyclophosphamide
Phenoxymethylpenicillin

15

Patient instructions

1. Adhere strictly to diet and medication regimens to avoid long-term consequences
2. Diet should be low in salt, water, and fat. Protein restriction, if advised, should be done cautiously to avoid malnutrition.
3. Frequent follow-ups will be required to achieve aggressive BP goals and to monitor disease progression by protein in urine and renal functions (every 3-6 months, then less frequently)

16

Mechanism of Focal segmental glomerulosclerosis

Hyalinosis: amorphous plasma
protein deposition-->
obliterates capillary lumen
+injury of vessel wall-->
focal glomerulosclerosis

Sclerosis: accumulation of collagen
seen +in diabetic nephroscleorsis
obliteraion of capillary lumen

17

Mechanism of BM thickening

+Protein synthesis
Deposition->immune complexes, amyloid

18

Progression of injury to glomerulosclerosis

Reduction in renal mass due to injury
1. Systemic HTN->mesangial mass/ECcoagulation
3. Glomerular hypertrophy->endothelial injury= + permeability to proteins, podocytes cant proliferate following injury->proteinuria.

19

Mechanism of fibrosis

Ischemia, chronic inflammation
lose pericapillary blood supply
Proteinuria= direct injury and
activates tubular cells-->+adhesion molecules, cytokine, GF-->fibrosis

20

Pathogenesis of immune mediated GN

1. Cytotoxic antibodies
2. Circulating immune complex
deposition= DNA/tumor antigens,
infectious products
3. In situ immune complex
deposition-->intrinsic tissue antigens
(anti-GBM), planted antigens (exogenous, endogenous=DNA, proteins, immunoglobuline, immune complexes, IgA)
4. Cell mediated->activates compliment

a. Neutrophils and monocytes-->
activation complement, proteases,
ROS, +cytokines
b. Macrophages, T cells, NK=
antibody/CMI= epilethial cell
injury, +mediators
c. mesangial cells= +ROS,
cytokine, chemokines,
grwth factors, NO, ET
d. Platelets aggregate

21

Causes of nephritic syndrome

Post-infectious
IgA nephropathy
Membranoproliferative
SLE
Infetcive endocarditis
HSP
Vasculitic-> Polyangitis, churg-strauss

22

Clinical presentation of nephritic syndrome

Proteinuria
Hematuria
Azootemia
RBC casts
Oliguria
Hypertension
Edema

23

Pathogenesis of PSGN

Activation of compliment
Antigen-antibody deposition-->
+neutrophils, cytokines, etc=
damage

Few weeks following streptococcal infectioins

24

Laboratory findings: Urine, creatinine, UEC, LFT, albumin, ANA, USS, biopsy, complement

Urine: Oliguria, 2+ protein, RBC ++++, RBC & WBC casts.
24h urine: 0.5 g protein in 24h
Serum: creatinine = 0.14 (slightly elevated)
LFT, electrolytes, Full blood counts – Normal.
Serum albumin – normal ;
Antinuclear antibody (SLE) - Negative
Ultrasound of kidneys: normal
Renal biopsy – Glomerulonephritis*

25

Triad in neprhotic syndrome

Proteinuria
Hypoalbuminemia
Edema

26

Mechanism of edema, proteinuria in neprhotic

+glomerular permeability->proteinuria, reversal of protein:albumin, cannot compensate->reduced oncotic pressure= edema

27

Pathogenesis of hyperlipidemia and + infections in nephrotic, and +thrombosis

1. Lipids +: liver response to
reduced oncotic pressure,
altered transport of lipids,
reduced catabolism.
Lipiduria when lipoproteins leak
2. +Infections->loss of immunoglobulins
3. Thrombosis->loss of anticoagulants

28

Histological pathology on renal biopsy in neprhotic

glomerular pathology on renal biopsy:
ƒƒminimal change disease (or minimal lesion disease or nil disease) – i.e. glomeruli appear
normal on light microscopy
ƒƒmembranous glomerulopathy
ƒƒfocal segmental glomerulosclerosis (FSGS)
ƒƒmembranoproliferative glomerulonephritis
ƒƒnodular glomerulosclerosis

29

Causes of minimal change

Hodgkins lymphoma
NSAIDs
Steroids

30

Define minimal change disease

complete effacement of
podocyte foot process, lose
negative charge (lymphokines
reduce anion production).