Download LECTURE OUTLINE DISEASE MECHANISMS OF GN Complement

LECTURE OUTLINE
DISEASE MECHANISMS OF GN
Complement-leukocyte-mediated mechanism:
1. Complement activation
2. C5a (chemotactic) attracts neutrophils & monocytes
3. Damage caused by –
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Proteases – degrade GBM
Oxidants – gen. cell damage
Eicosanoids (arachidonic acid metabolite)
C5b-9 (MAC) - epithelial cell detachment
Platelets – aggregate in glom –
prostaglandins
 Epith, mes. & endoth. Secrete interleukin-1
Circulating complexes vs. In situ complexes
Pre-formed complexes – Post streptococcal
Deposited antigens – Heymann’s Nephritis
Glomerular antigens – Goodpasture’s syndrome
Localisation of complexes
Smallest molecules reach sub epithelial positions
Larger molecules remain subendothelially or
Migrate to the mesangial matrix
Benign Hypertension
NB renal disease ↔ hypertension a vicious circle
Afferent arterioles
Thickening, hyalinization of vessel wall
Fibrin & BM matrix deposition
Interlobular arteries
Early = medial hypertrophy
Later = fibrosis of media
≈ GLOMERULAR ISCHAEMIA = COAGULATIVE
NECROSIS OF RENAL TUFT WITH LATER FIBROSIS
& COMPLETE SCLEROSIS
Macroscopy
Small
Granular surface with dark red depressed scars
Microscopy
Fibrous tissue infiltrated by lymphocytes & plasma
cells
Malignant Hypertension
RAPID RISE IN BP
FIBRINOID NECROSIS in afferent arterioles also
Haemorrage
Crescent formation
Thrombosis
Interlobular arteries
Onion skin lesion of intima
Medial hypertrophy
Macroscopy
“flea-bitten” kidney i.e. cortical haem.
Smooth surface
Occasional small infarcts
CHRONIC RENAL FAILURE (CRF)
All progressive renal diseases end in CRF - know all the
diseases
Severity = monitor [serum urea] [creatinine] GFR
Surviving nephrons compensate –
HYPERTROPHY
INCREASED ACTIVITY (CONSTANT)
Sclerosis – increased filtration pressure
Efferent arteriole constriction
Increased “wear & tear” on glom.
EFFECTS OF CHRONIC RENAL FAILURE
1. Water & Electrolyte Balance – arrythmias &
hypertesnion
2. Disturbance of acid-base balance – Metabolic
acidosis
3. Uraemia – lethargy, anorexia, nausea, vomiting
4. Hormonal abnormalities – anaemia , renal
osteodystrophy
5. Hypertension & its consequences – cardiac failure &
stroke
6. Fibrinous exudates – heart, lung, colon
7. Haemorrhagic ulcers – in G.I.T
8. Immune depression – infections
INFECTIONS OF THE KIDNEY
Tubulointerstitial Nephritis (TIN) = group of inflammatory
diseases that primarily involve the tubules & interstitium.
Glom. Are spared or affected late
TIN of bactrerial eatiology commonly has prominent
involvement of renal pelvis hence the term
PYELONIPHRITIS
Pyelo- =pelvis
Pyo- = pus production
Interstitial nephritis (IN) is used to describe noninfectious
cases e.g.:
Drug damage to tubules
Hypokalaemia (metabolic disorders)
Irradiation
Immune reactions
Acute & Chronic categories are based on the clinical
features & character of the inflammatory exudates
reagardless of the etiology
Ascending infection associated with lower UTI
Or
Haematogenous spread by pyogenic organisms (less
common)
Acute Pyelonephritis
Clinical features:
Pyrexia
Nausea
Vomiting
Headaches
Rigors
Locally:
Frequency
Dysuria
Loin pain
Haematuria
Macroscopy
Streaks & wedges of suppuration in cortex
Pale streaks with surrounding congestion in
medullary rays
Acute congestion & swelling of pelvis &
parenchyma
Microscopy
Tubular destruction by abscess formation
Mainly interstitial inflammation
In tact tubules filled with pus cells
Glom. In tact
Urine
Microscopy – pus cells / bacteria / red cells / pus cell
casts
Chemical – proteinuria / haematuria
Bacteriology
Principle causative org. = enteric gram neg. rods
E.coli (most common)
Proteus
Klebsiella
Enterobacter
Pseudomonas
Aetiology
Women – cystitis / vesici-ureteric reflux during
micturition / pregnancy / urethral instrumentation i.e.
catheterisation & cystoscopy introduce bacteria into
bladder
Men – prostatic enlargement / urethral instrumentation
i.e. catheterisation & cystoscopy introduce bacteria
into bladder
Both Sexes – calculi / tumours in renal pelvis /
pressure effects of tumours on ureters / calculi in
ureters & tumours of bladder
Protective mechanisms:
Antimicrobial action of bladder wall
Flushing action during micturition
Consequently urine is sterile
IN outflow obstruction or bladder dysfunction:
Defense protective mechanisms are overwhelmed
Consequently stage is set for UTI
Obstruction at level of urinary bladder =
Incomplete emptying & increased residual vol. of urine=
In the presence of stasis any bacteria introduced into the
bladder for e.g. by catheterization can multiply
undisturbed without being flushed or destroyed by bladder
wall
Incompetence of the vesicoureteral orifice allows bacteria
to ascend the ureter into the pelvis i.e. VUR vesicoureteral
reflux
Intrarenal reflux = movement of urine from the renal pelvis
through small ducts into the renal palillae and parenchyma
Influence of urinary tract obstruction
1. stagnation of urine
2. vesico-ureteric reflux
3. catherterisationis carried out = mixed infection
Progress
Perinephric abscess
Papillary necrosis – in kidney poles – associated with
Obstruction
Diabetes
Analgesic nephropathy
Sickle cell anaemia
Severe hypotension
Healing
Recurrence
CP
CHRONIC PYELONEPHRITIS
Due to REPEATED ATTACKS of INFLAMMATION &
HEALING
REFLUX
CONGENITAL ANOMALIES
Pathogenesis:
Hypertension exacerbates pathology
MACROSOPY
MICROSCOPY
1. interstitial fibrosis
2. acute suppurative lesions (recent infection)
3. foci of dilatedw tubules in cortex – collecting
tubules destroyed – upper tubules dilate – develop
colloid casts – patchy atrophy & fibrosis
CLINICAL EFFECTS
LOSS OF RENAL CONCETRATING POWER
ACIDOSIS
URAEMIA (not in unilateral obstruction)
HYPERTENSION
NB Patient can still be passing large quantities of
dilute urine
CP CAUSES END STAGE RENAL FAILURE
RENAL FUNCTION & PREGNANCY
1.
2.
3.
4.
ACUTE PYELONEPHRITIS
PRE-ECLAMPSIA & ECLAMPSIA
ATN
BILATERAL CORTICAL NECROSIS
ACUTE TUBULAR NECROSIS
AETIOLOGY
Shock – haemorrhage / burns / trauma / acute
intestinal / incompatible transfusion / acute
pacnreatitis
Poisoning – carbonCl4 / cis-platinum / lithium /
mercury / antibiotics
MACROSCOPY
Cortex broad & pale
Markings absent
Enlarged Kidney
Grossly congested pyramids
Cut surfaces bulge due to oedema
LIST OF TUBULO-INTERSTITIAL DISEASES
1. ATN
2. Pyelonephritis (infective aetiology)
3. IN (interstitial nephritis)
Acute – 10-14 d post drug exposure
Drugs = methicillin / NSAIDs (mefenamic acid)
Symptoms = febrile / haematuria / prtoeinuria /
arthralgia
NB cause of ACUTE RENAL FAILURE
Chronic – idiopathic / interstitial fibrosis is key feature /
Inflammation with continual tubular damage
with tubular loss and atrophy
Many pnts present with CRF
4. Metabolic conditions e.g. gout / nephrocalcinosis /
hypokalaemia
Basic pathogenesis
5. Myeloma cast nephropathy
6. Renal Tubular Abnormalities
AETIOLOGY OF HAEMOLYTIC URAEMIC SYNDROME
1. Children with E.coli 0157 alimentary infection
(verocytotoxin)
2. Shock conditions e.g. abruptio placentae / endotoxic
shock
3. Malignant hypertension
4. Drugs e.g. contraception / immunosuppressive
drugs
COMPLICATIONS OF END STAGE THERAPIES