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)
Acute uric acid nephropathy
caused by a rapid deposition of uric acid crystals in renal tubules and collecting ducts, usually as a result of tumour lysis syndrome or an acute attack of gout.
Gouty nephropathy
Aka chronic urate nephropathy
- occurs in long standing hyperuricaemia
- fibrosis and granulomatous reaction develop against crystalline deposits of urate in damaged tubules and interstitium of kidneys.
Vascular diseases of kidney
1) Benign nephrosclerosis
2) Malignant nephrosclerosis
3) Renal artery stenosis
4) Atheroembolic renal disease
Benign nephrosclerosis overview
Due to benign hypertension, the characteristic changes:
1) thickening of the arterial walls due to medial smooth muscle hypertrophy, which is seen mainly in the arcuate and larger arteries
2) In the smaller arteries and the arterioles, intimal fibrous thickening and hyaline arteriolosclerosis are found
3) As a result of the blood vessel changes with subsequent narrowing and ischaemia, secondary glomerular sclerosis and tubular atrophy develop.
4) Both kidneys are moderately reduced in size.
5) A slow process, thus Renal function is only slightly impaired.
Benign nephrosclerosis changes
Gross:
- kidneys are moderately reduced in size
- thin cortex
- increase in peripelvic fat
- thick renal arteries
- no coarse scar
Malignant nephrosclerosis overview
- a medical emergency
- associated with malignant or accelerated phase of hypertension
- Severe and rapid progression of injuries to the kidneys
- the damage quickly becomes irreversible (If the blood pressure is not adequately controlled quick enough, irreversible chronic renal failure soon develops.)
Malignant nephrosclerosis changes
In the interlobular arteries and arteriole
- Mucoid and cellular fibrointimal proliferation (fibroblastic proliferation leading to intimal thickening)
- Necrotizing arteriolitis (fibrinoid necrosis of arterioles)
- Thrombosis
- Neutrophilic infiltration
In glomeruli:
- Necrotizing glomerulitis
- Thrombosis
- Neutrophilic infiltration
Kidney size change:
- dependent on whether there is a pre-existing benign phase of hypertension
Renal artery stenosis
- Usually caused by atheromatous plaque at the origin of the renal artery (atherosclerosis)
- important (since curable) though uncommon cause of hypertension
Changes:
- Ipsilateral kidney atrophy (size reduction)
- Profound tubular atrophy
- crowding of the glomeruli
- juxtaglomerular apparatus is hyperplastic
- increased renin granules
Atheroembolic renal disease
Cause: Fragments of atheroma arising from the aorta or the renal artery are dislodged and embolized to the kidney
Epidemiology: Patients usually are elderly, esp after surgery, catheterization of aorta, or streptokinase treatment
Prognosis: may cause a notable rise in serum creatinine or acute renal failure (esp. in cases of pre-event kidney impairment)
[Note]: The emboli can be recognized by the cholesterol crystals they contain
Congenital abnormalities of kidney - classifications
1) Abnormalities of amount of renal tissue
i) Agenesis
ii) Hypoplasia
2) anomalies of position, form and orientation
i) Ectopia
ii) Horseshoe kidney
3) Anomalies of differentiation
i) Polycystic disease (infantile form; adult form)
ii) Dysplasia
Kidney agenesis
- Failure of development of kidney(s)
- Rare
- unilateral 1:550
- bilateral 1:4000
- bilateral incompatible with life
- result in oligohydraminos (due to reduced in utero urine production), consequently Potter’s sequence
Hypoplasia of kidney(s)
- Congenitally small kidneys
- Rare
- difficult to differentiate from dysplasia or severly scarred kidney
- lead to oligohydraminios (due to reduced in utero urine production), consequently Potter’s sequence
Oligohydraminios
- Reduction in the amount of amniotic fluid
- Result from (bilateral) renal agenesis, (bilateral) renal hypoplasia, infantile polycystic disease etc. (due to reduced in utero urine production)
- lead to Potter’s sequence
Source of amniotic fluid
Urine produced by fetus in utero
Potter’s sequence
A result of significant oligohydraminios of whatever causes (e.g. bilaterla kidney agenesis or hypoplasia, infantile polycystic kidney disease, etc.); presented with:
- flattened facies
- positional abnormalities of hands and feet
- dislocation of hip
- hypoplastic lungs
Kidney ectopia
- Kidney may be found in the pelvis
- Simple ectopia (ipsilateral displacement)
- Crossed ectopia (contralateral displacement)
- often associated with other urological abnormalities
Horseshoe kidney
- fusion of kidneys
- 1:400-800
- fusion often seen in lower pole (90%)
Infantile polycystic kidney disease
- Rare
- Autosomal recessive
- incompatible with long extra-uterine life (early infantile death)
- leads to oligohydraminios and Potter’s sequence
- Bilateral kidney involvement
- Symmetrical enlargement of kidneys, shape preserved
- Kidney cysts are fusiform dilated collecting ducts arranged radially
- Cut surface of kidney shows spongy appearance
- Large Liver: multiple epithelium-lined cysts in the liver as well as proliferation of portal bile ducts and portal tract expansion (congenital hepatic fibrosis). Portal hypertension resulted.
- Hypoplastic Lungs (lead to neonatal respiratory failure)
Modes of death in infantile PCKD
1) Neonatal respiratory failure (due to hypoplastic lungs)
2) Neonatal renal failure
Hepatic effect of infantile PCKD
- Enlarged liver
- congenital hepatic fibrosis
- Multiple epithelium-lined cysts in liver
- proliferation of portal bile ducts
- portal tract expansion
- portal hypertension
[note: infantile PCKD aka polycystic kidney and hepatic disease]
Adult polycystic kidney disease overview
- Relatively common (gene frequency 1:1000)
- autosomal dominant form of bilateral cystic disease of the kidneys
- compatible with life, some patients living up to 70 years
Adult PCKD kidney pathology
- Bilaterally kidney involvement
- kidneys greatly enlarged and may weigh up to several kg.
- distorted kidney shape; surface is nodular because of presence of cysts of varying sizes
- Contents of the cysts: urine, blood or altered blood.
- Cysts located in cortex and medulla, many connected with collecting tubules
Adult PCKD associated features (other than kidneys)
- berry aneurysms of cerebral arteries (leading to subarachnoid hemorrhage)
- associated with polycystic liver (and less commonly spleen, lungs, pancreas
- diverticulosis of large intestines
Adult PCKD presentation
Presenting in middle age (4th-5th decade) with:
1) Abdominal mass
2) Pain
3) Haematuria
4) Hypertension
5) Gradual/chronic renal failure
[note: 15% of patients died from subarachnoid haemorrhage due to berry aneurysm of cerebral arteries)
Adult PCKD genetic types
Due to mutations affecting an autosomal gene:
1) PKD1, a polycystin gene on chromosome 16 (over 80% of the cases); or
2) PKD2, on chromosome 4 (disease usually milder)
Both types of APKD are largely phenotypically similar
APKD early diagnosis
- Ultrasound at teenage
- Molecular genetic studies, linkage studies - prenatal diagnosis
Acquired cystic kidney disease
Not congenital but developed in end stage renal failure after long period dialysis
- Need to be distinguished from Adult PKD
Renal Dysplasia Overview
- Sporadic disease, not hereditary
- Not pre-neoplastic
Renal Dysplasia pathology
- anomalous differentiation of metanephric duct, resulting in aberrant differentiation of metanephric blastema
- characterised by the presence of cartilage islands and primitive tubules
- Often associated with ureteric atresia or LUT/bladder outflow obstructive lesion
- Often unilateral, but can be bilateral, diffuse, segmental, or focal.
- with or without multiple cystic structure deforming the kidney
- affected kidney may be small or enlarged
multicystic kidney caused by renal dysplasia
usually a unilateral condition presenting in an infant
