Renal: Pathology - Renal tubular and interstitial disease Flashcards
What are the causes of acute tubular necrosis?
INTO:
Ischaemia
acute tubulointerstitial Nephritis
Toxins
Obstruction
Three causes of ischaemia which may precipitate ATN
- Hypoperfusion
- Ischaemia of intrarenal vesels (e.g. in malignant HTN, microscopic polyangiitis)
- Thrombotic conditions (e.g. HUS, TTP, DIC)
Four types of toxins which can cause ATN
- Radiocontrast dye
- Radiation
- Myoglobin/haemoglobin
- Drugs (e.g. gentamicin)
What is the difference in the distribution of necrosis and casts in ischaemic vs nephrotoxic ATN?
Ischaemic: less necrosis than in toxic ATN, more patchy, mostly affecting the PST and TAL
Toxic: necrosis +++ in PCT and PST
Both: casts from DCT to collecting ducts
What are the histologic features of ischaemic vs nephrotoxic ATN?
Ischaemic: focal tubular epithelial necrosis with large skip areas, BM rupture, luminal occlusion
Toxic: may be non-specific, some distinctive patterns seen with certain drugs
Describe the three phases of ATN and the clinical features of each
- Initiation: lasts 36hrs, slight decrease in UO and increase in BUN
- Maintenance: sustained oliguria (40-400ml/day, with increased BUN, Na+ and H2O overload, hyperkalaemia, metabolic acidosis, uraemia, needs supportive management including dialysis
- Recovery: increased UO up to 3L/day (tubules damaged so increased water and electrolyte loss), increased risk of infection, hypokalaemia, normalisation of BUN and Cr
List 8 broad causes of tubulointerstitial nephritis with examples
- Infection: pyelonephritis
- Toxins: drugs, heavy metals
- Metabolic disease: nephrocalcinosis
- Physical factors: chronic urinary tract obstruction
- Neoplasms: MM
- Immunologic reactions: sarcoidosis, Sjogren syndrome, transplant rejection
- Vascular diseases
- Miscellaneous: Balkan nephropathy
List 8 drugs that may cause tubulointerstitial nephritis
SMART Nephrons Are Crying
Sulfonamides
Methicillin
Ampicillin
Rifampin
Thiazides
NSAIDs
Allopurinol
Colchicine
Outline the pathophysiological mechanism of ischaemic ATN
Dominant causative organisms in UTI
Gram negative (85%)
E. coli most common (followed by Proteus, Klebsiella, Enterobacter, S. faecalis)
Common haematogenous organisms causative of pyelonephritis
Staphylococcus
E. coli
Common causatives organisms in ascending UTI
E. coli
Proetus
Enterobacter
What % of otherwise normal children have vesicoureteral reflux?
1-2%
Three complications of acute pyelonephritis, a brief description of each, and in what circumstances they occur
- Papillary necrosis: in diabetics and with urinary tract obstruction, coagulative necrosis
- Pyonephrosis: with total or almost total obstruction; renal pelvis, calyses and ureters filled with pus
- Perinephric abscess: extension of supp
Histologic findings in acute pyelonephritis
Patchy interstitial suppurative inflammation, intratubular aggregates of neutrophils, tubular necrosis
8 predisposing factors for acute pyelonephritis
- Obstruction
- Instrumentation (e.g. IDC)
- Vesicoureteral reflux
- Pregnancy (4-6% of women develop bactiuria during pregnancy and 20-40% of these will develop symptomatic UTI if not treated)
- Gender and age (age 1-40 more common in women, more common in males with increasing age due to prostatic enlargement and instrumentation)
- Preexisting renal lesions
- Diabetes mellitus
- Immunosuppression / immunodeficiency
What finding on urine sampling suggests pyelonephritis over lower UTI?
Pus casts (formed from neutrophils in tubules)
What viral pathogen is of importance in causing pyelonephritis in kidney transplant recipients? How is it treated?
Polyomavirus
Treated with reduction in immunosuppression
Define chronic pyelonephritis. What are its two forms and which is more common?
Chronic tubulointerstitial inflammation and renal scarring associated with pathologic involvement of calyces and pelvis
1. Reflux nephropathy (more common)
2. Chronic obstructive pyelonephritis
What organism is xanthogranulomatous pyelonephritis associated with?
Proteus
What is malignant nephrosclerosis?
Renal disease associated with malignant HTN
What are the two major histologic features in blood vessels seen in malignant HTN?
- Fibrinoid necrosis of arterioles
- Onion-skinning (intimal thickening and fine concentric layering of collagen within interlobular arteries/arterioles: correlates well with renal failure)
Describe the clinical presentation seen with typical HUS
Prodrome of flu-like symptoms or diarhoea
Sudden onset of bleeding manifestations (e.g. haematemesis, melaena), severe oliguria, and haematuria
Laboratory findings including microangiopathic haemolytic anaemia and thrombocytopaenia
What organism causes typical HUS?
E. coli strains that produce Shiga-like toxin (usually strain O157:H7)
Classical pentad of TTP
- Fever
- Neurologic symptoms
- Microangiopathic haemolytic anaemia
- Thrombocytopaenia
- Renal failure (thrombi seen in glomeruli)
Gene affected in TTP
ADAMTS13: affects cleavage of vWF –> promotes platelet aggregation
Inheritance pattern of polycystic kidney disease
AD
What is the typical affected demographic in TTP
Women <40yo
Five causes of atypical HUS
- Antiphospholipid syndrome (either primary or secondary to SLE)
- Complications of pregnancy (can occur 1 day to several months postpartum)
- Vascular renal disease (e.g. systemic sclerosis, malignant HTN)
- Chemotherapeutic and immunosuppressive drugs (e.g. cisplatin, cyclosporine, gemcitabine)
- Irradiation of kidney
How is atypical HUS distinguished from TTP?
Atypical HUS shows normal levels of ADAMTS13
Describe the pathophysiology of HUS
Shiga-like toxin induces endothelial injury –> endothelial activation–> platelet aggregation and intravascular thrombosis –> distal ischaemia
Four risk factors for haematogenous route of infection in pyelonephritis
- Presence of ureteral obstruction
- Debilitated patients
- Immunosuppression
- Non-enteric organisms (e.g. staphylococci, certain fungi, viruses)
