L15 - tub/int/vas & congenital diseases Flashcards
tubular and interstitial diseases relationship
Renal tubules and interstitium are anatomically closely related and are often considered together in diseases.
Four major groups of tubulo-interstitial diseases
A. Functional (inherited) disorders of the tubules
B. Acute tubular necrosis
C. Acute interstitial nephritis
D. Chronic interstitial nephritis
Inherited tubular disorders (source, gross and microscopic changes)
Source:
1) Primary defects in tubular reabsorption of substances, e.g.
- Renal glycosuria
- Cystinuria
- Fanconi syndrome
- Renal tubular acidosis
2) Secondary to toxic material accumulation due to inborn metabolic errors, e.g.
- Wilson’s disease
- Galactosaemia
Gross and microscopic changes are wither absent or nonspecific
Acute tubular necrosis Histology
- tubular epithelium undergoes sloughing with the production of granular casts
- regenerating epithelium is flattened and irregular.
- Mitotic figures are present.
- Inflammatory infiltrate is typically scanty or absent in ATN.
ATN causes
- Ischaemic damage (due to inadequate blood flow to peripheral organs, e.g. marked hypotension, shock, thrombosis, decreased ECV)
- Toxic damage (radiocontrast dyes, poisons, radiation, heavy metals, hemoglobin, myoglobin, drugs such as antibiotics like gentamicin)
[3. Acute tubulointerstitial nephritis (as a result of drug hypersensitivity)]
[4. Urinary obstruction (by tumours, prostatic hypertrophy, or blood clots)]
ATN signs and pathogenesis
The early stage of ATN is usually characterised by:
- oliguria
- uraemia,
- metabolic acidosis and
- hyperkalaemia.
Diuresis is usual in the recovery stage, when the patient passes large volumes of urine and may become dehydrated and hypokalaemic.
Recovery of renal function is usually good (injuries are reversible) though it may take a long time.
risk factors for ATN development
- Jaundiced patients are prone to have ATN
- rhabdomyolysis (myoglobinuria -> toxic injury of tubules)
- acute intravascular haemolysis (haemoglobinuria -> toxic injury of tubules).
Tubulointerstitial nephritis etiological agents
1) Infections
2) toxins
3) metabolic diseases
4) Physical factors
5) Immunologic reactions
6) Vascular diseases
7) Miscellaneous
Tubulointerstitial nephritis general histology
- inflammatory changes in the interstitium
- accompanied by various degrees of tubular loss and degeneration
Acute interstitial nephritis histology and prognosis
Histology:
1) The interstitium is edematous
2) Interstitium infiltrated by inflammatory cells
3) Tubular degeneration and regeneration may also be present.
Prognosis: Acute interstitial nephritis causes acute renal failure.
Chronic interstitial nephritis histology and presentation
Histology:
- prominent interstitial fibrosis
- inflammatory cell infiltration
- tubular atrophy.
Presentation:
- Producing chronic renal failure
- proteinuria,
- hypertension
- renal tubular dysfunction (e.g. renal glycosuria, aminoaciduria, phosphaturia, and failure to acidify or concentrate urine)
Classes of Infection-induced tubulointerstitial nephritis
1) Acute bacterial pyelonephritis
2) Chronic pyelonephritis
3) Other infections (fungi, viruses, parasites)
Definition of pyelonephritis
nephritis caused by bacterial infection
Acute pyelonephritis features
- caused by bacterial infection
- part of urinary tract infection
- in patients with UTI, infective organisms are usually derived from the patient’s fecal matter
Acute pyelonephritis routes of infection
1) Ascending
- commoner
- usually endogenous fecal pathogen
- associated with urine reflux
2) Hematogenous
- occurs in septicemia or infective endocarditis
- Non-enteric bacteria, such as staphylococcus and fungi
Chronic pyelonephritis
- Chronic tubulointerstitial inflammation and renal scarring
- associated with pathological involvement of calyces and pelvis
- infections play major role, but associated with urinary tract obstruction, and reflux of urine (reflux nephropathy)
Commonest etiology of acute interstitial nephritis
Drug-induced, usually antimicrobial drugs and diuretic agents, e.g.
- Methicillin, ampicillin
- Rifampicin
- Thiazide diuretics
- NSAIDs
- Others, e.g. phenindione, cimetidine
Acute drug-induced interstitial nephritis
- a hypersensitivity reaction
- occurs about 2 weeks after drug exposure
Presentation:
- Fever, oesinophilia, rash
- hematuria, proteinuria, leukocyturia
- Rising serum creatinine
- acute renal failure
Urate nephropathy
Another form of tubulointerstitial disease
- Acute uric acid nephropathy
- Gouty nephropathy (aka Chronic urate nephropathy)