Membranoproliferative Glomerulonephritis and ATI

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Questions and Answers

Which factor primarily contributes to the risk of pyelonephritis through bladder to kidney spread?

Increased physical activity

Increased fluid intake

Urinary tract obstruction and urine stasis (correct)

Low blood pressure

What role does vesicoureteral reflux play in kidney infections?

It prevents the spread of infection to the kidneys.

It has no significant impact on kidney infections.

It enhances the drainage of infected urine.

It allows retrograde urine movement, promoting infection. (correct)

Which symptom is indicative of renal involvement in establishing a diagnosis of kidney infections?

Frequency of urination

Renal casts (correct)

Dysuria

Fever

What is a common complication associated with urinary obstruction and diabetes mellitus in kidney infections?

Acute renal failure Signup and view all the answers

What characteristic finding is associated with polyomavirus nephropathy?

Nuclear enlargement and intranuclear inclusions Signup and view all the answers

What is the most common cause of acute kidney injury?

Acute Tubular Injury Signup and view all the answers

Which characteristic is NOT associated with the 'tram-track appearance' in pathology?

Cyst formation Signup and view all the answers

What factor is primarily responsible for decreased glomerular filtration rate (GFR) in acute tubular injury?

Intra-tubular obstruction Signup and view all the answers

Which of the following describes the pathogenesis of tubular injury in acute tubular injury/necrosis?

Loss of cellular polarity and redistribution of transport proteins Signup and view all the answers

In the context of acute tubular injury, which agent is least likely to cause nephrotoxic acute tubular injury?

Hyperhydration Signup and view all the answers

What determines the reversibility of acute tubular injury?

Presence of patchy damage allowing repair Signup and view all the answers

Which feature is common to both nephritic and nephrotic syndromes when severe?

Concomitant nephrotic-range proteinuria Signup and view all the answers

What role do leukocytes play in the pathogenesis of acute tubular injury?

They exacerbate the tubular injury through inflammation. Signup and view all the answers

What characterizes the Maintenance Phase of acute tubular injury?

Sustained decrease in urine and rising BUN concentrations Signup and view all the answers

Which bacteria are commonly responsible for urinary tract infections that lead to acute tubular injury?

Escherichia coli Signup and view all the answers

In chronic tubulointerstitial nephritis, what type of leukocyte infiltration is typically observed?

Predominantly mononuclear Signup and view all the answers

What is a common complication associated with the Recovery Phase of acute tubular injury?

Hypokalemia Signup and view all the answers

Which factor can lead to chronic pyelonephritis?

Vesicoureteral reflux Signup and view all the answers

What is the primary route for the ascending infection in UTIs?

Colonization of the distal urethra and urethra to bladder Signup and view all the answers

Which of the following statements about acute tubular injury is correct?

It is characterized by interstitial edema and tubular injury. Signup and view all the answers

What are common systemic effects of tubulointerstitial nephritis?

Azotemia and metabolic acidosis Signup and view all the answers

Study Notes

Membranoproliferative Glomerulonephritis (MPGN)

Type 3 MPGN is characterized by subendothelial, intramembranous, and subepithelial deposits seen on electron microscopy (EM).
Clinically, it presents with nephritic syndrome, which can progress to nephrotic syndrome if severe, with concomitant nephrotic-range proteinuria.
Light microscopy (LM) shows mesangial ingrowth, leading to glomerular basement membrane (GBM) thickening and splitting, creating a "tram-track" appearance.
A hallmark of MPGN is the duplication of the GBM.

Acute Tubular Injury/Necrosis (ATI)

ATI is defined as acute renal failure with evidence of tubular injury, often in the form of tubular epithelial cell necrosis.
The term "injury" is preferred, as it is not always necrotic.
ATI is the most common cause of acute kidney injury.
It is typically a reversible process.

Causes of ATI

Ischemic ATI Pattern: Caused by inadequate blood flow to the kidneys, leading to ischemia. Can be due to hypotension and shock.
Nephrotoxic ATI Pattern: Direct toxic injury to tubules by endogenous or exogenous agents. A wide range of toxic agents can cause this.
Mixed Patterns: Combinations of ischemic and nephrotoxic factors.

Pathogenesis of ATI

Tubular Injury:
- Proximal tubules are most sensitive to injury due to their toxin-concentrating abilities and high energy demands.
- Early reversible changes include loss of polarity due to redistribution of transport proteins.
- Tubuloglomerular feedback, triggered by increased sodium delivery to distal tubules, results in lower glomerular filtration rate (GFR).
- Leukocyte recruitment and inflammation worsen the injury.
- Later changes include cell detachment and luminal obstruction, increasing intratubular pressure and further reducing GFR.
- Leaking of tubular filtrate into the interstitium due to damaged endothelial cells increases interstitial pressure, further damaging tubules and decreasing GFR.
Persistent and Severe Blood Flow Disturbances:
- Intrarenal vasoconstriction further reduces GFR, leading to decreased blood flow and oxygen delivery.
- Production of endothelin increases, while nitric oxide and prostacyclin (prostaglandin 12) production decreases.

Reversibility of ATI

The patchy nature of damage allows non-damaged segments to repair and maintain renal function once the disturbance is removed.
Proliferation and differentiation of epithelial cells (re-epithelialization) contribute to reversibility.

Clinical Features of ATI

Initiation Phase (up to 36 hours): Slight decline in urine output and increase in blood urea nitrogen (BUN); oliguria (reduced urine output) due to decreased blood flow and declining GFR.
Maintenance Phase: Sustained decrease in urine output, salt and water overload, rising BUN concentrations, hyperkalemia, metabolic acidosis. This is a reversible stage.
Recovery Phase: Steady increase in urine output; large amounts of water, sodium, and potassium are lost due to damaged tubules. Hypokalemia (low potassium) arises, leading to increased risk of infection. Creatinine and BUN levels return to normal. Subtle, persistent functional impairment may occur for months, but eventually, complete recovery occurs.

Tubulointerstitial Nephritis

A group of renal diseases involving inflammation of the tubules and interstitium, often with an insidious onset.
Acute: Rapid clinical onset with interstitial edema, leukocytic infiltration, and tubular injury.
Chronic: Predominant mononuclear leukocyte infiltration, interstitial fibrosis, and widespread tubular atrophy.

Causes of Tubulointerstitial Nephritis

Focus on pyelonephritis and toxin-induced tubulointerstitial nephritis.

Pyelonephritis

One of the most common kidney diseases, defined as inflammation of the tubules, interstitium, and renal pelvis.
Acute: Typically caused by bacterial infection (UTI).
Chronic: Results from recurrent infections, often associated with vesicoureteral reflux and obstruction.
Affects the bladder (cystitis) and kidney and collecting ducts (pyelonephritis).
Lower UTIs can remain localized to the bladder or spread to the kidneys.

Pathogenesis of Pyelonephritis

More than 85% of UTIs are caused by gram-negative bacilli (normal intestinal flora).
Escherichia coli is the most common causative agent, followed by Proteus, Klebsiella, and Enterobacter.
Streptococcus faecalis and other bacteria, fungi, and viruses can also cause UTIs.
Viral causes (Polyomavirus, cytomegalovirus, adenovirus) are more common in kidney allografts and immunocompromised individuals.

Routes of Infection

Ascending infection:
- Colonization of the distal urethra (usually in females) by coliform bacteria.
- Spread from the urethra to the bladder. Catheterization is a common cause.
- Bladder to kidney spread is influenced by:
  - Urinary tract obstruction and urine stasis.
  - Vesicoureteral reflux (VUR): Impaired valve allows urine to flow back, facilitating progression to pyelonephritis. VUR can be congenital, exacerbated by bacterial infection, or promoted by spinal cord injuries.
  - Intrarenal reflux: Open ducts at the tips of the papillae.

Clinical Features of Pyelonephritis

Risk Factors:
Urinary tract obstruction
Instrumentation
Vesicoureteral reflux
Pregnancy
Gender and age
Preexisting renal lesions
Diabetes
Immunosuppression and immunodeficiency

Clinical Presentation

Sudden onset of pain at the costovertebral angle.
Systemic signs of infection, such as fever and malaise.
Urinary tract irritation (dysuria, frequency, urgency).
Pyuria (increased leukocytes in urine), which is not specific to kidney involvement.
Renal casts indicate renal involvement as they form within tubules.
Diagnosis confirmed by quantitative urine culture.
Antibiotic treatment typically resolves symptoms; however, recurrent infections are possible.

Viral Pyelonephritis (Polyomavirus Nephropathy):

Nuclear enlargement and intranuclear inclusions visible under the light microscope
Interstitial inflammatory response
Treatment: Reduction in immunosuppression

Complications of Pyelonephritis:

More serious manifestations and increased risk of recurrent infections in patients with urinary obstruction, diabetes mellitus, or immunodeficiency.
Papillary necrosis can lead to acute renal failure.

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Description

This quiz covers key aspects of Membranoproliferative Glomerulonephritis (MPGN) and Acute Tubular Injury/Necrosis (ATI). It examines the characteristics, clinical presentations, and causes of these renal conditions. Test your understanding of the pathophysiology and microscopy findings associated with MPGN and ATI.