9: Sepsis Flashcards
1
Q
What are the characteristic features and causes of ATI?
A
- Acute renal failure
- Morphologic evidence of tubular injury - necrosis of tubular epithelial cells
- Causes
○ Ischaemia due to reduced or interrupted blood flow
§ Diffuse involvement of intrarenal blood vessels
□ Microscopic polyangiitis
□ Microangiopathies
§ Decreased effective blood circulation
□ Hypovolaemic shock
○ Direct toxic injury to tubules
§ Endogenous agents
□ Myoglobin
□ Haemoglobin
□ Monoclonal light chains
□ Bile/bilirubin
§ Exogenous agents
□ Drugs
□ Radiocontrast dyes
□ Heavy metals
□ Organic solvents
2
Q
Pathogenesis of ATI
A
- Tubular cell injury
○ Tubular epithelial cells particularly sensitive to ischaemia and vulnerable to toxins
○ Several factors predispose tubules to toxic injury
§ Increased surface area for tubular reabsorption
§ Active transport systems for ions and organic acids
§ High rate of metabolism and oxygen consumptions required
§ Capability for resorption
§ Concentration of toxins
○ Ischaemia causes
§ Loss of cell polarity due to redistribution of membrane proteins from basolateral to luminal surface of tubular cells -> increased sodium delivery to distal tubules
□ Incites vasoconstriction via tubuloglomerular feedback
§ Lowers GFR to maintain distal blood flow
§ Ischaemia tubular cells express cytokines and adhesion molecules
□ Recruiting leukocytes
§ Injured cells detach from basement membranes and cause luminal obstruction, increased intratubular pressure and decrease GFR
§ Glomerular filtrate can leak back into interstitium -> interstitial oedema, increased interstitial pressure and further damage to the tubule- Disturbances in blood flow
○ Haemodynamic alterations cause reduced GFR
○ Intrarenal vasoconstriction
§ Reduced glomerular blood flow and reduced oxygen delivery
○ Several vasoconstrictive pathways implicated
§ Renin-angiotensin system - stimulated by decreased sodium in tubules as a result of decreased blood pressure
§ Sublethal endothelial injury
□ Increased release of vasoconstrictor endothelin and decreased production of vasodilators nitric oxide and prostaglandin I2
- Disturbances in blood flow
3
Q
Morphology of ATI
A
- Tubular epithelial injury at multiple points along nephron
- Occlusion of lumens by casts
4
Q
Stages of ATI
A
- Initiation phase
○ Lasts 36 hours
○ Dominated by inciting medical, surgical or obstetric event
○ Slight decline in urine output with a rise in BUN- Maintenance phase
○ Sustained decrease in urine output between 40 and 400ml/day
○ Salt and water overload
○ Rising BUN concentrations
○ Hyperkalaemia
○ Metabolic acidosis - Recovery phase
○ Increase in urine volume to 3L/day
○ Tubules damaged so large amounts of water, sodium and potassium lost
○ Hypokalaemia
○ Increased vulnerability to infection
○ BUN and creatinine levels return to normal
- Maintenance phase
5
Q
What is tubulointerstitial nephritis?
A
- Group of renal disease involves inflammatory injuries of the tubules and interstitium that are often insidious in onset
- Principally manifest by azotaemia
6
Q
Types of tubulointerstitial nephritis
A
- Acute ○ Rapid clinical onset ○ Characterised histologically by § Oedema § Leukocytic infiltration or interstitium and tubules - Chronic ○ Infiltration with mononuclear leukocytes ○ Prominent interstitial fibrosis ○ Widespread tubular atrophy - Secondary ○ Present in a variety of vascular, cystic (PKD) and metabolic (diabetes) renal disorders ○ Contribute to progressive damage
7
Q
Common causes of tubulointerstitial nephritis
A
- Infections ○ Acute bacterial pyelonephritis ○ Chronic pyelonephritis ○ Other infections - Toxins ○ Drugs ○ Acute-hypersensitivity interstitial nephritis ○ Analgesics ○ Heavy metals ○ Lead, cadmium - Metabolic diseases ○ Urate nephropathy ○ Nephrocalcinosis ○ Oxalate nephropathy - Physical factors ○ Chronic urinary tract obstruction ○ Neoplasms ○ Multiple myeloma - light-chain cast nephropathy - Immunologic reactions ○ Transplant rejection ○ Sjogren syndrome ○ Sarcoidosis - Vascular disease - Miscellaneous ○ Nephronophthisis ○ Idiopathic interstitial nephritis
8
Q
Define pyelonephritis
A
- Inflammation affecting the tubules, interstitium and renal pelvis
- Serious complication of urinary tract infection
9
Q
Pathogenesis of pyelonephritis
A
- Haematogenous infection ○ Commonly § Staphylococcus § E.coli ○ Bacteraemia spreads to kidneys - Ascending infection ○ Common agents § E.coli § Proteus § Enterobacter ○ Bacterial colonisation - usually via instrumentation ○ Bacteria enter bladder ○ Deranged vesicoureteral junction ○ Vesicoureteral reflux ○ Intrarenal reflux
10
Q
What conditions predispose to pyelonephritis?
A
- Urinary Tract Obstruction ○ Stasis of urine ○ BPH, tumours, calculi ○ Neurogenic bladder dysfunction - Vesicourethral Reflux ○ Incompetence of vesicourethral valve ○ Commonly congenital ○ Persistent bladder atony - Intrarenal Reflux ○ Infected urine projected up to renal pelvis ○ Most common in upper and lower poles - Immunosuppression ○ Chemotherapy ○ Corticosteroids ○ AIDS ○ Primary immune deficiency
11
Q
Clinical features of acute pyelonephritis
A
- Flank pain
- Myalgia
- Flu-like symptoms
- Raised temperature
- Nausea and vomiting
12
Q
Morphology of acute pyelonephritis
A
- Gross
○ Patchy inflammation and abscess formation
○ Patchy capsule surface
○ Cortical scarring
○ Papillary necrosis- Micro
○ Neutrophilic infiltration into tubules
- Micro
13
Q
Clinical features of chronic pyelonephritis
A
- Asymptomatic
- Recurrent acute symptoms
- Renal insufficiency and hypertension
- Polyuria and nocturia
- Proteinuria
14
Q
Morphology of chronic pyelonephritis
A
- Gross ○ Irregular cortico-medullary scarring ○ Loss of papillae and blunting of calyces - Micro ○ Inflammatory cell infiltrate ○ Presence of plasma cells ○ Fibrosis and scar formation ○ Thyroidisation - tubules show atrophy in some areas and hypertrophy/dilation in others ○ Sclerosed glomeruli
15
Q
What are the main complications resulting from urinary tract obstruction?
A
- Increase susceptibility to infection and stone formation
- Unrelieved obstruction almost always leads to permanent renal atrophy - hydronephrosis or obstructive uropathy
