Glomerular Disease Overview
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Questions and Answers

What is the commonest cause of nephrotic syndrome in children?

  • Focal Segmental Glomerulosclerosis
  • Diabetic nephropathy
  • IgA nephropathy
  • Minimal change glomerular nephritis (correct)

    • Which type of glomerular disease is most commonly associated with recurrent haematuria in young adults?

  • IgA nephropathy (correct)
  • Chronic kidney disease
  • Minimal change glomerular nephritis
  • Focal Segmental Glomerulosclerosis

    • What role do podocytes play in the structure of the glomerulus?

  • Regulating blood flow
  • Producing hormones
  • Lining the capillary network (correct)
  • Transporting nutrients

    • Which glomerular disease is the most prevalent cause of nephrotic syndrome in Sub-Saharan Africa?

    <p>Focal Segmental Glomerulosclerosis</p> Signup and view all the answers

    What is the approximate number of glomeruli in each human kidney?

    <p>600,000 to 1.2 million</p> Signup and view all the answers

    What is a defining characteristic of glomerular disease?

    <p>Abnormality of the glomerulus</p> Signup and view all the answers

    Which demographic is primarily affected by IgA nephropathy?

    <p>Young adults</p> Signup and view all the answers

    Why is focal segmental glomerulosclerosis particularly common in Sub-Saharan Africa?

    <p>Related to genetic background and high HIV rates</p> Signup and view all the answers

    Which statement about glomerular disease is false?

    <p>Minimal change glomerular nephritis primarily affects adults.</p> Signup and view all the answers

    Which IgG type is associated with glomerulonephritis (GN)?

    <p>IgG1</p> Signup and view all the answers

    What is the primary purpose of conducting urinalysis in patients with kidney disease?

    <p>To confirm renal pathological processes</p> Signup and view all the answers

    What causes the foamy appearance of urine in nephrotic syndrome?

    <p>Excess protein leakage</p> Signup and view all the answers

    In nephritic syndrome, the main characteristic symptom is:

    <p>Dark tea-colored urine with dysmorphic haematuria</p> Signup and view all the answers

    Which treatment is indicated to remove antibodies in cases of autoimmune glomerulonephritis?

    <p>Plasmapheresis</p> Signup and view all the answers

    What primarily determines the treatment approach in nephrotic syndrome?

    <p>Underlying disease process</p> Signup and view all the answers

    What characterizes primary glomerular disease?

    <p>The glomerulus is the sole or predominant tissue affected.</p> Signup and view all the answers

    What happens to the immune system when damage occurs within the glomerular capillaries?

    <p>The immune system remains unaware of the damage.</p> Signup and view all the answers

    Which of the following is a feature of Alport's syndrome?

    <p>It involves hereditary abnormalities in collagen.</p> Signup and view all the answers

    What is true about secondary glomerular disease?

    <p>It is related to systemic diseases that target the glomeruli.</p> Signup and view all the answers

    What type of hematuria is associated with abnormalities in the glomerular basement membrane without activation of the immune system?

    <p>Asymptomatic hematuria</p> Signup and view all the answers

    What is the primary effect of thin basement membrane lesions?

    <p>They lead to glomerular (dysmorphic) hematuria.</p> Signup and view all the answers

    What does podocytopathy specifically refer to?

    <p>Damage to the podocytes themselves.</p> Signup and view all the answers

    Why is there typically no inflammatory response in structural abnormalities of the glomerular basement membrane?

    <p>No abnormal proteins stimulate the immune system.</p> Signup and view all the answers

    What type of disease results from immune complexes that provoke an inflammatory reaction in the glomeruli?

    <p>Proliferative disease</p> Signup and view all the answers

    In glomerulonephritis, what primarily causes inflammation?

    <p>Immune response to filtering damage.</p> Signup and view all the answers

    What contributes primarily to the development of nephrotic syndrome?

    <p>Excessive loss of protein in the urine</p> Signup and view all the answers

    Which type of antibodies favors translocation through endothelial and glomerular basement membrane barriers?

    <p>IgG2 and IgG4</p> Signup and view all the answers

    Which of the following is NOT a result of direct damage to podocytes?

    <p>Glomerular hypertension</p> Signup and view all the answers

    What is a significant outcome of podocyte injury that does NOT cause nephrotic syndrome?

    <p>Minor damage to podocytes resulting in urine protein loss</p> Signup and view all the answers

    Which of the following factors can contribute to podocyte injury?

    <p>Hypertension and ischemic conditions</p> Signup and view all the answers

    What is the primary feature of podocytopathy?

    <p>Significant proteinuria and nephrotic syndrome</p> Signup and view all the answers

    What physiological response occurs in podocytes during injury?

    <p>Foot process effacement and effusion</p> Signup and view all the answers

    What type of proteinuria typically results from extrarenal factors?

    <p>Extra-glomerular proteinuria</p> Signup and view all the answers

    What explains the normal electrolyte levels in U&E despite significant proteinuria?

    <p>Intact tubular function compensates for protein loss</p> Signup and view all the answers

    Which of the following disorders can lead to damage of podocytes?

    <p>Diabetes mellitus and heroin use</p> Signup and view all the answers

    What is the initial effect of antigen binding to an antibody in the context of glomerulonephritis?

    <p>It can cause damage to the tissues leading to injury.</p> Signup and view all the answers

    How does complement activation contribute to tissue damage in glomerulonephritis?

    <p>It forms a membrane attack complex that damages surrounding tissue.</p> Signup and view all the answers

    What role do white blood cells play after complement activation?

    <p>They promote further damage to the glomerulus.</p> Signup and view all the answers

    Which condition is noted for its ability to activate complement in glomerulonephritis?

    <p>Post infectious glomerulonephritis</p> Signup and view all the answers

    What is a common response of the remaining cells to injury in proliferative glomerular diseases?

    <p>They proliferate to replace lost cells.</p> Signup and view all the answers

    What does increased white cell presence in the urine indicate in context of glomerulonephritis?

    <p>Increased complement activation and immune response.</p> Signup and view all the answers

    The degree of complement activation in glomerular diseases is related to what?

    <p>The deposition of immune complexes in the mesangial sub-endothelium.</p> Signup and view all the answers

    Which type of cellular proliferation is associated with extra capillary glomerular disease?

    <p>Bowman’s epithelium proliferation.</p> Signup and view all the answers

    What mechanism is thought to enhance the damage to the glomerulus in glomerulonephritis?

    <p>Activation of a self-augmenting system.</p> Signup and view all the answers

    Which of the following is not a specific trigger for complement activation in glomerulonephritis?

    <p>Chronic liver disease</p> Signup and view all the answers

    Study Notes

    Glomerular Disease

    • Commonest cause of End Stage Kidney Disease in Europe and the US
    • Minimal change glomerular nephritis is the commonest cause of nephrotic syndrome in children
    • IgA nephropathy is the commonest cause of recurrent haematuria in young adults
    • Focal Segmental Glomerulosclerosis is the commonest cause of nephrotic syndrome in Sub-Saharan Africa
    • Often referred to as "FSGS" in Sub-Saharan Africa due to high prevalence of HIV and specific genetic background

    Definition

    • Any abnormality of the glomerulus
    • The glomerulus is responsible for filtering blood in the kidneys, each kidney contains between 600,000 and 1.2 million glomeruli
    • Each glomerulus consists of a network of capillaries lined by specialized cells called podocytes
    • Podocytes create a barrier to prevent large proteins from entering the urine
    • Damage to podocytes is known as "podocytopathy" and can be caused by various factors

    Types of Glomerular Disease

    • Primary Glomerular Disease: Disease directly affecting the glomeruli, cause may be idiopathic or related to immune system dysfunction
    • Secondary Glomerular Disease: Glomerular injury is a manifestation of a systemic disease, the glomerular injury is either directly targeted or accidentally targeted

    Structural Abnormalities of the Glomerular Basement Membrane

    • Abnormalities in the collagen structure of the basement membrane can affect endothelial and podocyte attachment, leading to blood cells being squeezed out into the urine, known as asymptomatic haematuria
    • Two key structural abnormalities:
      • Thin Basement Membrane: Glomerular basement membrane is thinner than normal
      • Alport's Syndrome: Abnormalities in collagen lead to a loosely woven basement membrane, affecting podocytes
    • Both are inherited abnormalities with genetic contributions

    Glomerulonephritis

    • Inflammation and damage to the glomeruli
    • Causes:
      • Immune complexes: Antibodies specific to podocytes can pass the basement membrane and be deposited on podocytes, leading to damage (IgG2/IgG4 conformation favors this)
      • Infection of podocytes: HIV, Parvovirus B19, live attenuated vaccines
      • Drugs: Interferon (IFN) used to treat multiple sclerosis
      • Ischemia: O2 deprivation to podocytes, often caused by hypertension, diabetes mellitus, ACE inhibitors, or heroin
      • Inherited defects of structure: Mutations in genes controlling cytoskeletal structure, like NEPH1, APOL1/MYH9 are more prevalent in Sub-Saharan Africa
    • These mutations may protect against sleeping sickness but cause damage to podocytes

    Functional Anatomy Determines Presentation

    • Damage to different parts of the glomerulus leads to specific clinical presentations
    • Damage to the podocyte filtration barrier leads to significant protein loss into the urine, resulting in nephrotic syndrome
    • Damage to other parts of the glomerulus, including the basement membrane, can trigger an inflammatory response, leading to glomerulonephritis

    Clinical Presentation Depends on the Histology

    • Podocyte damage leads to larger gaps in the filtration barrier, allowing more protein into the urine
    • Podocytopathies include non-immunological or inflammatory damage such as ischemic forms or minor damage, as well as genetic damage to glomerular structure
    • Podocytes respond predictably to injury, with foot process effacement and effusion being hallmark features
    • Foot process effacement: Podocytes detach from the basement membrane and spread out, disrupting the filtration barrier and leading to protein leakage

    Clinical Consequences of Proteinuria: Development of Nephrotic Syndrome

    • Excessive protein loss (over 3.5g in 24 hours)
    • Hypalbuminaemia (low blood albumin levels) leads to reduced oncotic pressure and fluid retention
    • Malnutrition due to protein loss increases risk of infection
    • Loss of immunoglobulins increases susceptibility to infections
    • Loss of coagulation factors increases risk of thrombosis
    • Loss of regulatory factors disrupts cholesterol balance

    Complement Activation in Glomerular Injury

    • The degree of complement activation is a key indicator of disease severity
    • Complement activation can lead to:
      • Complement mediated cytotoxicity: Membrane attack complex damages surrounding tissue
      • Recruitment of white cells: Chemotaxis attracts white cells to the inflammation site, causing further damage
    • The presence of white cells in urine (proteinuria) indicates complement activation and is an important diagnostic tool

    Antigens/Antibodies Implicated in Glomerulonephritis

    • Certain diseases are more likely to activate complement, including:
      • Post-infectious glomerulonephritis
      • Lupus
      • Other illnesses

    Proliferative Glomerular Diseases

    • Non-specific response to injury where remaining cells of a specific type proliferate to replace lost cells

    • Proliferation of endothelium, mesangium, and Bowman's epithelium contribute to glomerular damage

    • Cellular proliferation is often related to complex deposition in the mesangium and sub-endothelium

    • The degree of complement activation seems to play a role in cellular proliferation### Lupus-Associated Nephropathy

    • Lupus nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE).

    • Anti-dsDNA antibodies are a key diagnostic marker for SLE and can affect the kidneys.

    • Mechanism of Injury: Immune complexes form in the glomeruli, leading to inflammation.

    • Types of Lupus Nephritis: Classified by the type of IgG antibodies involved:

      • IgG 2 or 4 : Podocytopathy (damage to podocytes)
      • IgG1: Glomerulonephritis (GN)

    Modifying Factors in Glomerulonephritis

    • Ethnic Origin and Genetics:

      • APOL1 Mutation: Associated with increased risk of kidney disease, particularly in individuals of African descent. This mutation arose as protection against Schistosomiasis.
      • Caucasoid Origin: European or Asian ancestry tend to include autoimmune abnormalities

    • HIV:

      • HIV affects multiple immune cells including regulatory T cells, causing immune dysregulation, and thus affecting kidney disease expression and outcome.
      • Influences clinical presentation based on ethnic origin and pre-existing mutations.
      • May lead to a spectrum of kidney disease, from nephrotic to nephritic syndrome
      • Patient presentation, treatment, and prognosis are more important than classifying as nephrotic vs nephritic.

    History and Examination

    • Presenting Symptoms:

      • Swelling: Extremities, especially around the eyes (periorbital edema)
      • General Edema: Ankle edema, anasarca (generalized edema), ascites, pleural effusion (fluid in the lungs).
      • Foamy or Bubbly Urine: Indicates excess protein in urine.
      • Dark Urine: Tea-colored urine, dysmorphic hematuria (abnormal RBCs in urine) - indicative of nephritis.
      • Decreased Urine Output (Oliguria): A common symptom of kidney disease
      • Fatigue and Weakness: Due to impaired kidney function

    • Examination:

      • Urinalysis: ESSENTIAL to assess renal function. Both dipstick and laboratory analysis are required.

    Urinalysis

    • Purpose: To screen for and confirm kidney disease.
    • Dipstick: Provides a semi-quantitative assessment.
    • Lab analysis: Provides a more accurate and detailed assessment of urine constituents.
      • Urine Protein:Creatinine Ratio: Measures the amount of protein in the urine.
      • Microscopy: Examines the urine for cells, casts, and crystals.
    • Essential Steps:
      • Proper Collection: Clean meatus with saline, fresh midstream urine (early morning), analyze timeously.
      • Dipstick Quality: Check expiration date, store correctly.
    • Caveats: The longer urine sits, the more it deteriorates, impacting analysis.

    Nephrotic Syndrome vs. Nephritic Syndrome

    • Nephrotic Syndrome
      • Key Feature: Excessive protein loss in urine.
      • Diagnostic Criteria: > 3.5 g protein loss in a 24-hour urine collection.
      • Spot Urine Protein:Creatinine Ratio can also be used for diagnosis.
    • Nephritic Syndrome
      • Key Feature: Inflammation and damage of the glomeruli.
      • Diagnostic Criteria: >80% of red blood cells (RBCs) in urine must be dysmorphic.
    • Spectrum of Disease: Nephrotic and nephritic syndromes represent a spectrum of kidney disease.

    Glomerulonephritis: Treatment

    • Goal: Remove the underlying cause of kidney damage.
      • Remove Antigen:
        • Antibiotics: For post-streptococcal GN.
        • Antivirals: For hepatitis B (HBV) and hepatitis C (HCV) infections.
      • Remove Antibodies:
        • Plasmapheresis: Removes antibodies from the blood, used in severe cases.
        • High Dose Steroids: Reduce inflammation.
        • Cyclophosphamide: Suppresses immune response (chemotherapy).
        • MMF (Mycophenolate Mofetil); AZA (Azathioprine) ; Rituximab: Immunosuppressant medications.
    • Prognosis: Depends on the underlying cause and severity of the glomerular injury.
    • Referral: It's crucial to consult specialists for diagnosis and treatment.

    Nephrotic Syndrome: Treatment

    • Symptomatic Treatment: Treats complications such as edema and high blood pressure.
    • Specific Treatment: Targets underlying cause, can include:
      • ACEI (Angiotensin-Converting Enzyme Inhibitors) & Statins: Help to protect the kidneys by improving podocyte function.
    • Referral: Essential to find the underlying cause and receive specialized care.

    Histology and Clinical Presentation

    • Histological Damage: Underlying damage to the glomerulus determines the clinical presentation.
    • Podocyte Damage: Leads to proteinuria (key feature of nephrotic syndrome).
    • Four Histological Patterns:
      • Minimal Change Disease (MCD): Mildest form of podocyte damage.
      • Membranous Nephropathy (MN): More severe podocyte damage.
      • Crescentic Glomerulonephritis (CGN): Severe form with glomerular crescent formation.
      • Focal Segmental Glomerulosclerosis (FSGS): Scarring in some glomeruli.
    • Progressive Nature: As the severity of the histological damage increases, clinical manifestations become more severe.

    Disease Processes and Glomerular Damage

    • Various Kidney Disease Factors: Contribute to different types of glomerular damage.
    • Patient and Disease Factors: Influence presentation, prognosis, and treatment options.

    Glomerular Vulnerability

    • High Blood Flow: Increases the risk of exposure to immune complexes, toxins, and blood-borne infections.
    • Ultrafilter Characteristics: The glomerular filter retains proteins, leading to extensive deposition of immune complexes.
    • Surface Area: The large glomerular surface area makes it vulnerable to inflammatory injury from circulating leukocytes.
    • Glomerular Pressure: Podocytes are already under strain, making them susceptible to damage from increased intraglomerular pressure.

    Key Takeaways

    • Disease Process and Patient Factors: Determine the type of glomerular injury and disease presentation.
    • Histological pattern: Guides diagnosis, treatment, and prognosis.
    • Single Disease Process: Can manifest as multiple histological forms of injury.
    • Similar Histology: Can be caused by diverse disease processes.
    • Oedema: Requires evaluation for nephritic or nephrotic syndrome.

    Lecture 2: An Approach to Proteinuria

    • Proteinuria: A hallmark of nephrotic syndrome.
    • Diagnostic Criteria: > 3.5 g protein loss in a 24-hour urine collection.
    • Spot Urine Protein:Creatinine Ratio: Can also be used for diagnosis.
    • Oedema: A common symptom associated with proteinuria.
    • Hypalbuminaemia: Low protein in the blood, a result of protein loss in the urine.

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    Clinical Sciences 22.10 - Glomerular Diseases PDF

    Description

    Explore the various types of glomerular diseases and their impacts on kidney function. This quiz covers causes of nephrotic syndrome and end stage kidney disease, alongside definitions and mechanisms involved in glomeruli. Delve into the conditions affecting different demographics, including children and young adults.

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