Glomerulonephritis Flashcards Preview

Internal Medicine > Glomerulonephritis > Flashcards

Flashcards in Glomerulonephritis Deck (45):
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).

31

In an adult what do you need to be mindful of in MCD

Association with Hodgkin's lymphoma

32

Pathogenesis of IgA nephropathy

Deposition of polymeric IgA in mesangium w/
adherence of compliment-->activation
May have +IgA following GIT/Respiratory infection

33

In what group is IgA nephropathy more common

Celiac
Ankylosing spondylitis
Alcoholic liver disease->reduced clearance

34

What is FSGN

Sclerosis of some,
not all glomeruli (focal)
and within glomerulus only
part of it has sclerosis
(segmental)

35

Etiology of FSGN

Etiology>idipathic, HIV/heroin/sickle
cell, reflux nephropathy
scarring of previously necrotising,
adaptive response (-ve renal mass,
intrarenal compensation,
membrane damage, ECM expansion), inherited

36

Comparison between MCD and FSGN

compared to MCD: +hematuria,
-ve GFR, HTN
+non selective proteinuria
Xresponse to steroids
+chronic development 50% in ten years
seen more in adults

37

Pathogenesis of diabetic nephrosclerosis

PKC, AGE, polyol pathways=
thickening, +BM proliferation,
-ve fibrinolysis

initially +GFR-->+intraglomerular
pressure, +glomerular
proliferation/hypertrophy, +glomerular
filtration area. In response to
ablation of renal mass.

38

Pathogenesis of hypertensive neuropathy

Hyaline-->hyaline thickening
w/ luminal narrowing-->
hemodynamic stress and injury-->
plasma protein leakage.
Hyperplastic-->in malignant
HTN-->
smooth muscle cell proliferation,
fibrinoid deposits and vessel wall necrosis

39

Causes of Rapidly progressive glomeruloneprhitis

Type 1- anti-GBM antibody--> renal limited, Goodpasture (associated pulmonary hemorrhage) IgG deposits on renal antigen + C3-->injury-->formation of crescents

Type 2 immune complex= idiopathic, post infectious, lupus nephritis, Henoch-schonlein--> granular pattern of immune complex deposition, cellular proliferation and crescents

Type 3 pauci immune Xanti-GBM antibodies ANCA +ve, wegeners, microscopic polyangtis

40

Management of neprhotic->general measures

1. Admit to hospital. Discuss with renal
2. Monitor UEC, BP, fluid balance and weight
2. Determine and treat underlying cause
3. Salt restriction and fluid restriction, daily weights
4. IV 20% albumin + Frusemide if IV depletion, severe/symptomatic edema
5. ACEi to reduce proteinuria!!!
6. Treat infections->give pneumococcal vaccination + phenoxymethylpenicillin prophylaxis
7. Avoid prolonged bed rest, give DVT prophylaxis if immobile
8. Smoking, alcohol, diet, exercise
9. Statins
10. Iron and vitamin D may be needed
11. Tight glycemic control
12. Ranitidine
13. Prednisilone to introduce remission, then wean
14. Family education->urine protein testing every morning, give booklet
15. After remissison->urine protein checked daily 1-2 years to ID a relapse
16. If relapse, prednisilone prior to edema
17. 80% chance of relapse, usually respond well
18. Most common trigger is intercurrent infection

41

Prognosis in nephrotic

1. Relapses are common
2. If child steroid resistant->biopsy and consider cyclophosphamide
3. Long term good prognosis

42

Assessment of neprhotic in children

1. History:
Oedema, weight gain, poor urine output, dizziness, or discomfort as a result of the oedema (including abdominal pain).
a. Mild (subtle peri-orbital region, scrotum or labia)
b. Moderate with peripheral pitting oedema of the limbs and sacrum.
c. Severe with gross limb oedema, ascites and pleural effusions.
2. Investigations
Heavy proteinuria (dipstick 3-4+ or urine protein/creatinine ratio >0.2g/mmol)
Hypoalbuminaemia (12y
Systemic symptoms of fever, rash, joint pains (SLE).
Persistent hypertension (can have mild hypertension first 1-2 days)
5. Rule out any nephritic features (requiring entirely different management)
Macroscopic haematuria (INS may have microscopic haematuria)
Hypertension
Raised serum creatinine (INS may have mild elevation with mod-severe volume depletion)
6. Assess for severity and complications of INS
a. Intravascular volume depletion
Dizziness, abdominal cramps
Peripheral hypoperfusion (cold hands or feet, mottling, capillary refill time > 2 seconds), tachycardia, oligoanuria, low urinary sodium, hypotension (late sign)
Severe/symptomatic oedema – potential skin breakdown/cellulitis, gross scrotal/vulval oedema, increased work of breathing from pleural effusion
b. Infection (at increased risk in nephrotic state)
Cellulitis from gross oedema with skin compromise
Spontaneous bacterial peritonitis – abdominal pain, fever, nausea/vomiting, rebound tenderness
c. Thrombosis (at increased risk in nephrotic state)
Deep vein thrombosis, pulmonary embolus
Renal vein thrombosis – macroscopic haematuria, palpable kidney, loin tenderness, raised creatinine, hypertension
Cerebral vein thrombosis - headache, vomiting, impaired conscious state or focal neurology

43

Investigations in nephrotic

1. Urine
Dipstick
Microscopy
Spot urine pro:cr
Sodium (volume depletion)
2. Bloods
FBC
UEC, LFT (albumin)
C3 and 4 (low in SLE and MPGN)
ANA (SLE)
Hep B if risk factors
Varicella serology

44

Define a relapse of neprhotic

1. Proteinuria 3+ or 4+ for 3 consequetive days
Need prompt administration of prednisilone

45

Considerations for steroid dependence in children/relpase of nephrotic

1. Infections->need additional booster
2. Vitamin D deficiency (lost in urine)
3. Hyperlipidemia
4. Hypothyroid->lost in urine
5. BMD
6. Eye examination after 12 months