Nephritic Syndrome

Name: Nephritic Syndrome
Uploaded: 2023-06-30T14:00:34.000Z
Duration: 2 h 58 min 49 s

Nephritic Syndrome: Understanding the Glomerular Filtration Barrier

Introduction to Nephritic Syndrome

The video discusses nephritic syndrome, a type of glomerulonephritis, emphasizing the importance of understanding the anatomy and function of the glomerular filtration barrier.

Viewers are encouraged to support the channel by liking, commenting, and subscribing. Additional resources such as notes and illustrations are available on their website.

Anatomy of the Glomerular Filtration Barrier

The glomerular filtration barrier (GFB) consists of three main components essential for its function.

Components of the GFB

Fenestrated Capillaries

These capillaries have small pores that allow plasma and certain substances to filter from blood into Bowman’s space while preventing larger elements like red blood cells from leaking out.

Glomerular Basement Membrane (GBM)

This membrane is negatively charged due to its protein composition, which repels similarly charged proteins in plasma, thus preventing their leakage into Bowman’s space.

Podocytes

These specialized cells line the filtration barrier with foot processes creating filtration slits that regulate permeability while blocking large entities like red blood cells and proteins.

Functionality of the GFB

The primary role of the GFB is to selectively allow small molecules (e.g., amino acids, glucose, electrolytes) to pass through while blocking larger components such as red blood cells and proteins.

In nephritic syndrome, damage occurs specifically to the GBM leading to compromised filtration capabilities.

Pathophysiology of Nephritic Syndrome

Nephritic syndrome results from damage or dysfunction in the GBM which disrupts its ability to control what passes into Bowman’s space.

This dysfunction leads to leakage of red blood cells, white blood cells, and proteins into urine—characteristics defining nephritic syndrome compared with nephrotic syndrome where podocyte damage predominates.

Clinical Implications

Patients with nephritic syndrome exhibit symptoms related to GBM injury including hematuria (blood in urine), proteinuria (increased protein in urine), and sterile pyuria (white blood cells without infection).

Understanding Nephritic Syndrome and Its Characteristics

Key Features of Nephritic Syndrome

The presence of white blood cells and proteins in urine is significant, indicating kidney issues. Patients often exhibit hematuria, characterized by a high number of red blood cells in the urine.

Hematuria is defined as the presence of red blood cells in urine, which occurs due to glomerular basement membrane damage leading to increased loss of red blood cells, white blood cells, and proteins.

In nephritic syndrome, protein loss is less than 3.5 grams per day (sub-nephrotic range), contrasting with nephrotic syndrome where it exceeds this threshold.

Red blood cells can take on tubular shapes when they get trapped in kidney tubules, forming what are known as "red blood cell casts," which are specific indicators of glomerular disease.

Acanthocytes may also appear in the urine; these damaged red blood cells indicate ongoing renal pathology associated with nephritic syndrome.

Urinary Findings and Their Implications

The presence of white blood cells leads to sterile pyuria; however, unlike urinary tract infections (UTIs), there will be no significant bacterial presence or positive leukocyte esterase/nitrites tests.

In nephritic syndrome, while there are many white blood cells present in the urine, decreased bacteria levels differentiate it from UTIs.

Proteinuria remains under 3.5 grams per day without significant hypoalbuminemia or deficiencies in antithrombin III or immunoglobulins—key differences from nephrotic syndrome.

Clinical Consequences and Risks

The absence of significant hypoalbuminemia means patients with nephritic syndrome do not typically experience edema or complications like deep vein thrombosis (DVT).

Unlike nephrotic syndrome patients who face higher risks for chronic kidney disease (CKD), those with nephritic syndrome have a greater likelihood of acute kidney injury and renal failure.

Damage to the glomerular basement membrane results in an influx of proteins and white blood cells into Bowman's space—a critical area for understanding renal function impairment.

Summary Insights on Nephritis vs. Nephrosis

Nephrotic syndrome can lead to chronic kidney disease through conditions such as focal segmental glomerulosclerosis and diabetic nephropathy; however, nephritic syndrome poses a more immediate risk for acute kidney injury.

Understanding these distinctions between syndromes is crucial for effective diagnosis and treatment strategies within clinical practice related to renal health.

Understanding Nephritic Syndrome and Its Consequences

Pathophysiology of Nephritic Syndrome

The disease involves an increase in proteins, cytokines, fibrosis, sclerosis, and epithelial cell proliferation, leading to significant complications.

Epithelial cells in the Bowman's capsule proliferate excessively due to inflammation and cytokine release, occupying more space within the capsule.

This proliferation is accompanied by scarring (fibrosis and sclerosis), resulting in a crescent-shaped formation that indicates severe pathology.

The presence of glomerular crescents is alarming as it suggests impending renal failure; their formation severely impacts kidney function.

A drop in glomerular filtration rate (GFR) occurs due to these crescents obstructing filtrate flow, leading to various health issues.

Consequences of Low GFR

A low GFR results in the accumulation of waste products like blood urea nitrogen and creatinine, causing azotemia.

High levels of waste can progress to uremia, which may lead to neurological dysfunction and other systemic complications.

Activation of the renin-angiotensin-aldosterone system (RAAS) occurs with low GFR, contributing to increased blood pressure (hypertension).

Hypertension is a common consequence of nephritic syndrome due to fluid retention from impaired sodium and water filtration.

Edema develops as a result of sodium and water retention when GFR is compromised.

Summary of Key Issues Related to Nephritic Syndrome

The underlying cause includes damage or dysfunction of the glomerular basement membrane (GBM), leading to inflammatory responses that exacerbate fibrosis and cell proliferation.

Rapidly progressive glomerulonephritis can develop from these processes, significantly increasing the risk for renal failure compared to nephrotic syndrome.

Understanding GBM Damage and Nephritic Syndromes

Causes of Glomerular Basement Membrane (GBM) Damage

The discussion begins with the need to identify the causes of GBM damage, which leads to the loss of red blood cells, white blood cells, and proteins in urine.

Not all nephritic syndromes result in rapidly progressive glomerulonephritis; specific types will be discussed along with their causes.

Classification of Nephritic Syndromes

A systematic approach is suggested for understanding nephritic syndromes: categorize them as anti-GBM disease, ANCA vasculitis, hereditary nephritis, or immune complex deposition.

Anti-GBM Disease

Goodpasture syndrome is highlighted as a key example of anti-GBM disease characterized by hemoptysis and hematuria.

Patients have antibodies against the glomerular basement membrane that specifically target collagenous portions leading to inflammation and damage.

Mechanism of Injury in Goodpasture Syndrome

The binding of anti-GBM antibodies results in damage to both respiratory and glomerular membranes, causing leakage of red blood cells, white blood cells, and proteins into urine.

Clinical Features

Patients exhibit features typical of nephritic syndrome alongside hemoptysis due to alveolar capillary membrane damage.

ANCA Vasculitis Overview

Three types are identified: Granulomatosis with polyangiitis (GPA), Eosinophilic granulomatosis with polyangiitis (EPA), and Microscopic polyangiitis (MPA).

Immune Response Mechanism

ANCA antibodies do not deposit directly into the GBM but stimulate neutrophils and monocytes leading to inflammatory responses that cause vascular damage.

Distinguishing Features Among ANCA Types

Differentiation between C-anchor positive reactions associated with GPA versus P-anchor reactions is crucial for diagnosis.

Understanding Nephritic Syndromes and Their Implications

Key Differences in Nephritic Syndromes

Panka is linked with MPA (Microscopic Polyangiitis) and EPA (Eosinophilic Granulomatosis with Polyangiitis). Identifying GPA (Granulomatosis with Polyangiitis) can be straightforward, but distinguishing between MPA and EPA requires attention to eosinophil levels and asthma symptoms.

In cases of EPA, look for increased eosinophils and features indicative of asthma. This association is crucial for understanding the underlying pathology of these vasculitides.

Rapidly Progressive Glomerulonephritis (RPGN)

Both anti-GBM disease (Goodpasture syndrome) and ANCA-associated vasculitis can lead to RPGN, characterized by significant inflammatory responses that may result in acute renal failure.

The presence of glomerular crescents in these conditions indicates a high risk for early renal failure due to their impact on kidney function.

Hereditary Nephritis Overview

Hereditary nephritis is primarily genetic, often presenting in children. It is immune-mediated by white blood cells rather than antibodies.

Symptoms include hematuria, sensory-neural deafness, and lens dislocation due to mutations affecting type IV collagen, which compromises the integrity of the glomerular basement membrane.

Mechanisms Behind Hematuria

The mutation leading to decreased type IV collagen results in a dysfunctional glomerular basement membrane (GBM), causing leakage of red blood cells and proteins into urine.

Patients exhibit thin GBMs that contribute to their clinical presentation, including hematuria and proteinuria.

Immune Complex Deposition Disorders

Immune complex deposition disorders involve various mechanisms: anti-GBM disease involves antibody deposition; ANCA vasculitis involves immune cell deposits; hereditary nephritis results from inadequate GBM production.

Conditions like post-streptococcal glomerulonephritis are triggered by infections such as strep throat or impetigo, leading to specific immune responses.

Pathogenesis of Post-Streptococcal Glomerulonephritis

Following a strep infection, antibodies form against bacterial antigens. These complexes can deposit into the GBM after breaking off from the bacteria.

The formation of antibody-antigen complexes leads to subepithelial immune complex deposition within the GBM, resulting in inflammation through complement system activation.

This structured overview captures essential insights regarding nephritic syndromes discussed in the transcript while providing clear timestamps for further reference.

Understanding Complement Activation and Nephritis

Mechanism of Antibody Action

Antibodies bind to antigens, activating complement proteins (C3, C4, C5, C6), which are crucial for the immune response.

The activation of these complements leads to inflammation and damage to the glomerular basement membrane (GBM), resulting in loss of red blood cells, white blood cells, and proteins.

Post-Streptococcal Glomerulonephritis

In post-streptococcal glomerulonephritis, complement proteins are consumed during activation, leading to decreased levels of C3.

Continuous GBM damage can progress to rapidly progressive glomerulonephritis and potentially renal failure.

IGA Nephropathy Overview

IGA nephropathy is identified as a common nephritic syndrome that often follows upper respiratory or gastrointestinal infections.

IGA antibodies target specific antigens on pathogens but deposit in the mesangium rather than the GBM, causing localized inflammation without complement activation.

Clinical Presentation of IGA Nephropathy

Damage to the GBM results in hematuria but not nephrotic range proteinuria; key symptoms include loss of red blood cells and white blood cells into urine.

IGA antibodies may also deposit in skin (causing purpuric lesions), abdomen (abdominal pain), or joints (joint pain).

Differentiating Conditions: Henoch-Schönlein Purpura vs. IGA Nephropathy

Presence of vasculitic lesions alongside hematuria indicates Henoch-Schönlein purpura rather than isolated IGA nephropathy.

Lupus Nephritis Characteristics

Lupus nephritis is associated with a history of lupus; diagnostic features include malar rash and anemia.

Tissue damage releases nuclear material that binds with antibodies, contributing to disease pathology.

Antibodies and Immune Complexes in Glomerular Diseases

Overview of Antibodies

The discussion begins with the introduction of specific antibodies: anti-nuclear antibodies and anti-double-stranded DNA antibodies, which bind to particular antigens.

These antibodies can deposit in various locations within the kidney, specifically sub-epithelial and sub-endothelial areas, leading to immune complex deposition.

Mechanism of Damage

The presence of immune complexes activates the complement system (C3), resulting in C3 consumption and subsequent damage to the glomerular basement membrane (GBM).

This GBM damage leads to the presence of red blood cells, white blood cells, and protein in urine. Notably, this condition can present as nephrotic range proteinuria despite being classified under nephritic syndrome.

Clinical Correlations

Lupus nephritis is highlighted as a condition that can cause rapidly progressive glomerulonephritis (RPGN), along with IGA nephropathy and post-streptococcal glomerulonephritis.

It is emphasized that not all conditions lead to RPGN; hereditary nephritis and membranoproliferative glomerulonephritis do not present with this feature.

Membranoproliferative Glomerulonephritis (MPGN)

MPGN is often idiopathic but can be secondary to infections like Hepatitis B/C or cryoglobulinemia.

There are two types of MPGN: Type 1 involves unknown antigens or infections leading to immune complex formation that deposits into the GBM.

Type 2 MPGN Insights

Type 2 MPGN features an antibody known as "nephritic factor," which binds with C3 convertase, enhancing its activity. This binding results in increased inflammation and further GBM damage.

Understanding Nephritic and Nephrotic Syndromes

Mechanism of C3 Convertase Activation

The molecule C3 convertase, when bound by an antibody, becomes hyperactive, leading to the conversion of C3 into C3a and C3b. This process is highly effective in increasing these proteins' levels.

Impact on Glomerular Basement Membrane (GBM)

Increased deposition of C3a and C3b proteins occurs in the glomerular basement membrane (GBM), resulting in significant damage to the GBM structure. This damage manifests as dense deposits within the membrane.

Clinical Manifestations of GBM Damage

Damage to the GBM leads to various clinical symptoms including:

Loss of red blood cells (hematuria) in urine.

Loss of white blood cells (possible sterile pyuria).

Protein loss, which can indicate nephrotic range proteinuria depending on the syndrome type.

Differentiating Nephritic from Nephrotic Syndromes

Key differences between nephritic and nephrotic syndromes include:

Nephritic Syndrome: Characterized by glomerular basement membrane dysfunction with hematuria and sub-nephrotic range proteinuria.

Nephrotic Syndrome: Defined by podocyte dysfunction leading to heavy proteinuria (>3.5g/day) and lipiduria.

Diagnostic Features via Urinalysis

Urinalysis plays a crucial role in differentiating between nephritic and nephrotic syndromes:

Nephrotic Syndrome: Shows heavy proteinuria, often quantified as +3 or +4 on dipstick tests; presence of fat oval bodies under microscopy.

Nephritic Syndrome: Typically presents with hematuria (red blood cell casts) and may show white blood cells without bacteria (sterile pyuria). Protein levels are usually lower than those seen in nephrotic syndrome unless exceptions like lupus nephritis or membranoproliferative glomerulonephritis occur.

Nephrotic vs. Nephritic Syndrome: Key Differences and Diagnosis

Understanding Protein Loss in Nephrotic Syndrome

The next step in assessing nephrotic syndrome involves quantifying protein loss, specifically determining if it exceeds 3.5 grams per day.

Nephrotic syndrome is characterized by podocyte dysfunction and glomerular basement membrane dysfunction, which are crucial for understanding proteinuria levels.

A 24-hour urine protein collection or a one-time spot urine albumin-creatinine ratio can effectively quantify protein loss, with the latter being a convenient option.

Distinguishing Between Nephrotic and Nephritic Syndromes

In nephrotic syndromes, proteinuria is greater than or equal to 3.5 grams per day; in contrast, nephritic syndromes typically show less than this threshold.

Exceptions to this rule include lupus nephritis and membranoproliferative glomerulonephritis, where patients may present with significant proteinuria despite having features of nephritic syndrome.

Renal Function Decline in Glomerulonephritis

A decline in renal function is critical for differentiating between nephrotic and nephritic syndromes; nephritic syndromes pose a higher risk of acute kidney injury (AKI).

Patients with nephritic syndromes often experience rapid renal failure due to conditions like rapidly progressive glomerulonephritis.

Laboratory Indicators of Kidney Injury

Testing renal function through BMP reveals increased BUN and creatinine levels alongside decreased GFR, indicating glomerular injury more commonly seen in nephritic syndromes.

While both types can lead to chronic kidney disease (CKD), AKI is more prevalent in cases of nephritic syndrome.

Diagnosing Specific Causes of Nephritic Syndrome

Identifying the specific cause of nephritic syndrome requires further investigation into potential underlying conditions such as anti-glomerular basement membrane (GBM) disease or vasculitis.

For anti-GBM disease diagnosis, look for hemoptysis symptoms and positive anti-glomerular basement membrane antibodies as key indicators.

Vasculitis Considerations in Diagnosis

In cases suggesting ANCA vasculitis, testing for ANCA positivity is essential; a positive C-ANCA indicates granulomatosis with polyangiitis (GPA).

Chronic sinusitis may also be an important diagnostic clue when evaluating GPA alongside features of nephritic syndrome.

Differentiating Between Eosinophilic Polyangiitis and Microscopic Polyangiitis

Key Differences in Symptoms

Eosinophilic polyangiitis (EPA) is characterized by asthma and eosinophilia, while microscopic polyangiitis does not present with these features.

In EPA, patients may exhibit other allergy-related symptoms, which can help in distinguishing it from microscopic polyangiitis.

Hereditary Nephritis and Alport Syndrome

Important indicators of Alport syndrome include sensory neural deafness and anterior lenticonus (lens problems).

These features are often assessed through clinical tests like Weber's and Rinne's tests to evaluate hearing loss.

Understanding Immune Complex Deposition

Identifying Post-Streptococcal Glomerulonephritis

Look for positive anti-ASO and anti-DNase B antibodies as indicators of post-streptococcal glomerulonephritis.

A recent strep infection (1 to 2 weeks prior) is a critical historical cue; be cautious about the timing of symptoms.

Complement Levels in Diagnosis

Low C3 levels suggest conditions such as post-streptococcal glomerulonephritis, lupus nephritis, or membranoproliferative glomerulonephritis.

If C3 levels are low alongside positive anti-nuclear antibodies or anti-double-stranded DNA antibodies, consider lupus nephritis.

Navigating Complex Diagnoses

Differentiating Conditions Based on Antibodies

Positive anti-nuclear antibodies indicate lupus nephritis; look for a history of systemic lupus erythematosus (SLE).

Membranoproliferative glomerulonephritis typically does not show low C3 levels, making it easier to differentiate from other conditions.

Biopsy Considerations

For unclear cases, a biopsy may be necessary to confirm membranoproliferative glomerulonephritis due to its complex nature.

Evaluating Normal C3 Levels

Investigating IgA Nephropathy

If C3 levels are normal, testing for IgA antibodies can be done but may lack specificity.

Evidence of IgA vasculitis should be sought through symptoms like skin lesions or gastrointestinal issues following an upper respiratory tract infection within 1 to 2 days.

Understanding Nephritic Syndrome Diagnosis

Initial Assessment of C3 Levels

The first step in diagnosing nephritic syndrome involves checking C3 levels. Low C3 levels suggest specific conditions, while normal levels may indicate other issues.

If the patient's history aligns with symptoms and C3 levels are normal, one should consider common types of nephritic syndrome.

Role of Renal Biopsy

A renal biopsy is essential when the cause of nephritic syndrome is unclear or if the patient shows signs of renal failure or persistent hematuria that does not respond to treatment.

During a biopsy, kidney tissue is examined using three microscopy techniques: light microscopy for general changes, electron microscopy for detailed glomerular basement membrane (GBM) analysis, and immunofluorescence to identify antibodies or immune complexes.

Microscopy Findings and Their Implications

Light microscopy can reveal significant changes in the glomerulus; crescents observed may indicate rapidly progressive glomerulonephritis (RPGN).

RPGN can be associated with several diseases including anti-glomerular basement membrane disease (Goodpasture's), ANCA vasculitis, post-streptococcal glomerulonephritis, IgA nephropathy, and lupus nephritis.

Identifying Specific Conditions

If no crescents are present in the biopsy results, consider hereditary nephritis and membranoproliferative glomerulonephritis (MPGN).

MPGN type 1 and type 2 show unique features under light and electron microscopy; mesangial cells invade GBM leading to a "tram track" appearance.

Distinguishing Between Types

The "tram track sign" is crucial for identifying MPGN types 1 and 2. This finding indicates immune complex deposition.

Alport syndrome presents differently with thin or split GBM due to Type IV collagen deficiency; this condition can be diagnosed without further testing if identified on light microscopy.

Final Diagnostic Considerations

For anti-GBM disease (Goodpasture's), only one type shows linear antibody deposition on immunofluorescence.

ANCA vasculitis lacks immune complex deposition; it’s important to differentiate it from other conditions that do show such deposits.

Granular patterns could indicate post-streptococcal infections, IgA nephropathy, lupus nephritis, or MPGN types 1 and 2. Further investigation may be necessary based on findings.

Nephritic Syndrome: Differentiation and Treatment Strategies

Granular Appearance in Nephritic Syndromes

The granular appearance can indicate various conditions such as PSGN, lupus nephritis, MPGN1, and MPGN2. Each has distinct characteristics.

A "lumpy bumpy" appearance is typically associated with subepithelial deposition in PSGN, while both subepithelial and sub-endothelial depositions are seen in lupus nephritis.

Biopsy and Immunofluorescence Insights

If serology does not clarify the diagnosis, a biopsy may be necessary to examine light microscopy for crescents; their presence indicates potential nephritic syndrome.

Differentiating between types involves looking at the granular appearance: lumpy bumpy for PSGN, immune complex deposition for MPGN1 (sub-endothelial), and C3 dense deposits for MPGN2. Additionally, mesangial deposition indicates IgA nephropathy.

Treatment Approaches for Nephritic Syndrome

Treatment primarily focuses on managing complications like proteinuria through dietary adjustments and medications such as ACE inhibitors or ARBs to alleviate edema by affecting the efferent arterioles.

In cases of hypertension due to low GFR activating the renin-angiotensin system, ACE inhibitors or ARBs are recommended to mitigate this issue effectively.

Managing Rapidly Progressive Glomerulonephritis (RPGN)

RPGN can arise from conditions like anti-GBM disease, ANCA vasculitis, post-streptococcal glomerulonephritis, IgA nephropathy, and lupus nephritis; these require prompt treatment with steroids initially.

If renal function declines despite steroid treatment, plasmapheresis may be indicated specifically for anti-GBM disease and ANCA vasculitis to remove harmful immune complexes from circulation.

Long-term Management Strategies

For stable renal function but ongoing risk of disease progression in RPGN or MPGN cases, long-term immunosuppressants like cyclophosphamide or tacrolimus may be necessary to prevent further damage.

Nephritic Syndrome Management

Overview of Glomerulonephritis Treatment

Plasmapheresis is generally not indicated for membranoproliferative glomerulonephritis (MPGN); it is primarily used in rapidly progressive glomerulonephritis (RPGN).

RPGN and MPGN can be treated with steroids acutely, especially if renal function continues to deteriorate.

In cases of anti-glomerular basement membrane (anti-GBM) disease or ANCA vasculitis, plasmapheresis may be considered if renal function remains stable.

Long-term Management Strategies

To prevent the progression of RPGN or MPGN, long-term immunosuppressants such as cyclophosphamide or tacrolimus can be added to the treatment regimen.

The video concludes with a discussion on nephritic syndrome, emphasizing the importance of understanding these management strategies.