Flashcards in L77 - Kidney Diseases II Deck (91):
What are the 2 major groups of processes in renal tubule diseases?
1) Acute tubular injury and acute renal failure
2) Tubulointerstitial nephritis
What is Acute tubular injury and acute renal failure mostly due to?
Ischaemic or toxic injury
What is Tubulointerstitial nephritis mostly caused by?
Inflammatory reactions of tubules and interstitium
What is another name for acute tubular injury?
Acute tubular necrosis
How does acute tubular injury present?
As Acute renal failure
Tubular injury is the most common cause of acute renal failure
Describe acute renal failure?
Clinicopathologic entity with clinical acute deterioration of renal function
Associated with morphologic evidence of tubular injury
Give 3 examples of ischaemia that causes acute renal failure?
Decreased effective circulating blood volume (e.g. shock)
Diffuse involvement of intrarenal blood vessels (e.g. malignant hypertension)
Thrombosis (e.g. thrombotic microangiopathy)
Give examples of direct toxic injury that causes acute renal failure?
Give 3 examples of urinary obstruction that causes acute renal failure?
By prostatic hypertrophy
Apart from ischaemia, urinary obstruction, direct toxic injury, name one cause of acute renal failure?
Acute Tubulointerstitial nephritis
[Acute tubular injury appearance under light microscopy?
Necrotic tubular epithelium sloughed in tubules
Dilated tubules with flattened tubular epithelium
3 stages of acute tubular injury?
What is initiation phase in acute tubular injury?
Slight decline in urine output with rise in blood urea and creatinine
(lasting for about 36 hours)
What is maintenance phase in acute tubular injury?
Decrease in urine output 40-400 mL/day (oliguria),
salt and water overload,
rising blood urea and creatinine,
What is Recovery phase in acute tubular injury?
Steady increase in urine volume, up to 3L/day,
leading to loss of large amount of water, sodium and potassium
What is the outcome in acute tubular injury?
supportive care >> most patients can recover
What can delay recovery in acute tubular injury?
conditions like sepsis, extensive burns and multi-organ failure
What is affected in Tubulointerstitial nephritis?
• Inflammatory injuries of the tubules AND interstitium
• Glomeruli are spared
How does acute Tubulointerstitial nephritis manifest?
presented as acute or
subacute worsening of renal function:
• Raised blood urea and creatinine level
• Usually 2 weeks after drug exposure
What is the number 1 cause of Tubulointerstitial nephirits?
What are other causes of Tubulointerstitial nephritis?
• Metabolic diseases
• Physical factors
• Immunologic reactions
What infections can cause Tubulointerstitial nephritis?
Acute and Chronic pyelonephritis
What Metabolic diseases can cause Tubulointerstitial nephritis?
2) Acute phosphate
5) Acute phosphate
What neoplasms can cause Tubulointerstitial nephritis?
• Multiple myeloma (light chain cast nephropathy)
What physical factors can cause Tubulointerstitial nephritis?
Chronic urinary tract obstruction
What immunologic reactions can cause Tubulointerstitial nephritis?
Sarcoidosis, Sjogren’s disease
What are the top causative drugs causing tubulointestinal nephritis?
All drug classes
Especially NSAID, Antibiotic, Antivirals, Diuretics
WHat reaction occurs that cause tubulointerstitial nephrritis? How to allevaite problems?
Hypersensitivity reaction to medication
Identification and withdrawal of the culprit drug
3 histology features of Tubulointestinal nephritis?
• Interstitial inflammation
>>Abundant eosinophils points to drug cause
>> Inflammatory cells in between tubular cells
• Interstitial edema (acute) or fibrosis (chronic)
Light microscopy appearance of drug-induced acute tubulointerstitial nephritis?
Large amount of inflammatory cells including eosinophils (stained red) in the interstitium and tubulitis
What does Pyelonephritis affect?
tubules, interstitium and renal pelvis
2 major forms of pyelonephritis?
• Acute pyelonephritis
• Chronic pyelonephritis
What is acute pyelonephritis? Caused by?
• Acute infection of kidney, generally caused by ascending bacteria infections
2 routes of acute pyelonephritis?
• Acute pyelonephritis
• Chronic pyelonephritis
What are some common predisposing causes of acute pyelonephritis?
• Lower urinary tract infection
• Urinary tract obstruction
• Vesico-ureteric reflux
What are some less common predisposing causes of acute pyelonephritis?
• Instrumentation / catheterization of urinary tract
• Immunosuppression and
What are some presenting symptoms of acute pyelonephritis?
What is a presenting symptoms of acute pyelonephritis Specific to bhildren?
Failure to thrive
Name the common pathogens that cause Acute pyelonephritis?
• Mycobacterium Tuberculosis (TB) ***
• Other bacteria and fungal infections
What are other bacteria (not Mtb) that can cause acute pyelonephritis?
• Escherichia coli (E. coli)
• Strptococcus faecalis
Gross appearance of urinary tract of acute pyelonephritis?
Multifoci abscess and pus formation
Light microscopic appearance of urinary tract of acute pyelonephritis?
(infection extend up to Bowman's capsule)
Large amount of neutrophils in interstitium and tubules + other inflammatory cells
Treatment of acute pyelonephritis?
appropriate antibiotic therapy depending on the inciting pathogen
Outcome of acute pyelonephritis?
• Symptoms usually disappear in a few days
• Usually complete resolution without leaving significant effects on kidney
Describe the healing process of acute pyelonephritis?
• Neutrophilic infiltrates replaced by macrophages, plasma cells and
• Scattered scar formation
Name 2 complications of acute pyelonephritis?
>> Pus in renal pelvis, calyces and ureter
• Perinephric abscess
>> Extension of pus through renal capsule into perinephric tissue
Describe chronic pyelonephritis?
Chronic inflammation in tubules and interstitium (Tuberculosis excluded)
>> Scarred kidney caused by repeated bacterial infections
What is chronic pyelonephritis associated with?
• Vesico-ureteric reflux
• Urinary tract obstruction (stone, stricture)
Is Chronic pyelonephritis bilateral or unilateral?
• Involvement usually unequal on the two sides
How does the scar formation in chronic pyelonephritis change the morphology of kidney?
Scar tissue is depressed/ shrunken
Symptoms of recurrent acute pyelonephritis?
• High fever
• Shaking chills
• Loin pain
What are the early stage symptoms of chronic pyelonephritis?
subtle/no symptoms in early stage
>> Polyuria and nocturia due to loss of tubular function in concentrating urine and resorption of water
Name one symptom of chronic renal failure and end stage kidney disease?
Explain how chronic pyelonephritis lead to FSGS?
FSGS = nephrotic
• Decrease in number of functional glomeruli due to loss of nephron unit
• Compensatory hypertrophy by remaining glomeruli (due to increased renal blood pressure)
• Progressive fibrosis involving portions of some glomeruli due to compensatory action >. FSGS
Are microscopic findings diagnostic for chronic pyelonephritis?
Treatment for chronic pyelonephritis?
• Treat possible underlying causes
• Treat recurrent acute pyelonephritis by antibiotic therapy
Outcome of Chronic pyelonephritis?
• Depends on extent of scarring:
If loss of significant amount of renal tissue = End stage renal disease
What is the Dx for this case:
Unknown herbal medicine intake
Epigastric pain and vomiting with oligouria
Normal kidney size and WBC levels
Need microscopy to diagnose
What are the microscopic features of light chain cast nephropathy?
Tubular casts rimmed by
macrophages revealed by both PAS stain and H&E stain
Lambda light chain restriction
What is Lambda light chain restriction?
In reactive lymphoid populations there is a mixture of kappa and of lambda positive cells,
>> cells expressing kappa light chains outnumbering cells expressing lambda light chains >> lambda light chain restriction
What is the cause of light chain cast nephropathy?
Neoplasm > multiple myeloma = neoplasm of plasma cells
What age group does light chain cast nephropathy affect?
90% of cases greater than age of 50 years old (median age 70 years old)
Presentation of Light chain cast nephropathy?
Acute renal failure and proteinuria
Other renal diseases associated with monoclonal light chains?
• Amyloidosis (AL type)
• Light chain deposition disease
• Light chain proximal tubulopathy
Treatment for Light chain cast nephropathy?
• Treat underlying plasma cell neoplasm
• Hematopoietic stem cell transplantation in selected case
Outcome of Light chain cast nephropathy?
• 5-year survival rate: 20-25%
Name 4 important vascular diseases that lead to renal disease?
* only remember top 4*
• Hypertensive nephrosclerosis
• Malignant nephrosclerosis (malignant hypertension)
• Diabetic nephropathy
• ANCA-associated vasculitis
(Atheroemboli, Renal artery stenosis, Thrombotic microangiopathy)
Diabetic nephropathy affects which structures?
Affecting both vessels and glomeruli
Pathology of Hypertensive nephrosclerosis causing Extravasation of plasma protein ?
Hypertension >> Sclerosis of renal arterioles and small arteries
>> Hyalinization of arteriolar wall
>> Extravasation of plasma protein through injured endothelium
Changes to renal arterioles in Hypertensive nephrosclerosis?
Intimal fibrosis and medial thickening
How does Hypertensive nephrosclerosis lead to gradual decline in renal function?
Affected vessels have thickened walls and narrowed lumens
>> ischaemia and subsequent glomerulosclerosis and chronic tubulointerstitial injury
>> gradual decline in renal function
Light microscopy appearance of Hypertensive Nephrosclerosis? **important**
Glomerulosclerosis and Hyaline arterolosclerosis
Intimal fibrosis and medial
thickening of artery
What is Malignant nephrosclerosis associated with?
• Associated with malignant or accelerated hypertension
What is the criteria for malignant hypertension?
Systolic pressure greater than 200 mmHg and/or diastolic pressure
greater than 120 mmHg
Presentation of malignant nephrosclerosis?
acute renal failure
Papilloedema (optic disc swelling), retinal haemorrhages,
Light microscopic appearance of Malignant nephrosclerosis?
• Fibrinoid necrosis of arteriole
• Hyperplastic arteriolitis (onion-skin lesion)
Treatment of malignant nephrosclerosis?
• Prompt and aggressive antihypertensive medication
Which type of diabetes can lead to diabetic nephropathy?
• Both Type I and Type II Diabetes mellitus (DM)
3 histological features of Diabetic nephropathy on the glomeruli?
• Thickened GBM (increase ground substance)
• Diffuse increase in mesangial matrix
• Kimmelstiel-Wilson nodules (deposition of basement membrane nodules)
How does Diabetic nephropathy lead to gradual decline in renal function?
Leading to ischaemia and subsequent glomerulosclerosis
> chronic tubulointerstitial injury > gradual decline in renal function
What forms in renal vasculature?
Leading to ischaemia and subsequent glomerulosclerosis and chronic tubulointerstitial injury
histological features of Diabetic nephropathy on the renal arterioles?
Hyalinosis of both afferent
and efferent arterioles
What is the EM appearance of GBM in Diabetic nephropathy?
GBM thickened to more than 1000nm, at least twice as thick as GBM
What type of glomerulonephritis is caused by ANCA-associated vasculitis?
rapidly progressive (crescentic) glomerulonephritis
Type III, Pauci-immune
Why is ANCA-associated vasculitis Pauci-immune?
Lack of detectable anti-GBM antibodies or immune complex
by direct immunofluorescence and electron microscopy
Name the 2 circulating antibodies in ANCA-associated vasculitis?
• c-ANCA (cytoplasmic)
• p-ANCA (perinuclear)
What is the full name of ANCA?
antineutrophil cytoplasmic antibodies
What are the 2 disease entities of ANCA-associated vasculitis?
granulomatosis with polyangiitis
What replaces vessel walls in ANCA- associated vasculitis?
Pathology of ANCA-associated vasculitis?
Injury to glomerular tufts >> leakage of plasma protein stimulates Bowman’s
>> parietal epithelium proliferates
>> hypercellular glomeruli
with crescentic glomerulonephritis