Urinary and Renal Disorders - Glomerular Disorders - Midterm Notes PDF

6 URINARY AND RENAL DISORDERS – Glomerular Disorders Glomerulonephri,s Overview Glomerulonephri-s refers to inflamma,on of the glomerulus within the kidney. It can be acute or chronic and is a significant cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD). 1. Most Likely Cause...

6 URINARY AND RENAL DISORDERS – Glomerular Disorders Glomerulonephri,s Overview Glomerulonephri-s refers to inflamma,on of the glomerulus within the kidney. It can be acute or chronic and is a significant cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD). 1. Most Likely Cause The causes of glomerulonephri-s can be categorized into primary (affec-ng the glomeruli directly) or secondary (due to systemic diseases) causes. Primary Causes: o Immunological Responses: § Type II hypersensi,vity: An-bodies aCack specific components of the glomerular basement membrane (as seen in Goodpasture syndrome). § Type III hypersensi,vity: Deposi-on of immune complexes (e.g., post- streptococcal glomerulonephri,s) in the glomerulus, triggering inflamma-on. § Type IV hypersensi,vity: T-cell-mediated injury, although less common o Infec,ons: § Post-streptococcal glomerulonephri,s (PSGN) is a common cause following a Streptococcus infec,on of the throat or skin. o Ischemia: Reduc-on in renal blood flow leads to glomerular damage. o Medica,ons & Toxins: Certain drugs and toxins can injure the glomeruli. o Free Radicals: Oxida-ve stress contributes to glomerular damage. o Vascular Disorders: Condi-ons like hypertension can lead to glomerular injury. Secondary Causes: o Diabetes Mellitus: Leads to diabe,c nephropathy, which is the most common cause of chronic glomerulonephri-s【121:0†source】. o Lupus (SLE): Systemic lupus erythematosus (SLE) can cause lupus nephri,s, a form of glomerulonephri-s【121:1†source】. 2. Pathophysiology The pathophysiology of glomerulonephri-s depends on the cause but generally involves an immune-mediated aRack on the glomerulus. 1. Immune Complex Deposi,on: o An,gen-an,body complexes (Type III hypersensi-vity) deposit in the glomerular basement membrane (GBM) following an infec-on, such as post-streptococcal glomerulonephri,s【121:1†source】. o The deposi-on of immune complexes triggers the ac-va-on of complement proteins, which recruit neutrophils and macrophages that release inflammatory cytokines【121:1†source】. 2. Cell-mediated Injury:  o Type IV hypersensi,vity involves T-cell aCack on glomerular cells, leading to damage【121:1†source】. 3. Direct An,body ARack: o In Type II hypersensi,vity, an-bodies directly target glomerular structures, such as in Goodpasture syndrome, leading to inflamma-on and injury【121:1†source 】. 4. Endothelial Injury: o Endothelial cells lining the glomerular capillaries are injured, and the basement membrane becomes more permeable【121:1†source】. o Increased permeability allows proteins (proteinuria) and red blood cells (hematuria) to leak into the urine【121:1†source】. 5. Reduc,on in Glomerular Filtra,on Rate (GFR): o Damage to glomerular capillaries leads to glomerular swelling and capillary obstruc,on, reducing the GFR【121:1†source】. o Increased pressure in Bowman's capsule occurs, leading to decreased filtra-on 【121:1†source】. 6. Chronic Inflamma,on: o Chronic inflamma,on leads to fibrosis and scar ,ssue forma,on, which further impairs kidney func-on, o[en leading to chronic kidney disease (CKD)【 121:0†source】. 3. Disease Transmission Transmission: o Glomerulonephri-s is a non-infec,ous condi,on and is not directly transmissible between individuals【121:1†source】. o However, infec-ons that trigger immune responses, such as Streptococcus pyogenes infec-ons, may indirectly lead to glomerulonephri-s, but the infec-on itself is transmissible (not the kidney disease)【121:1†source】. 4. Risk Factors Risk factors for glomerulonephri-s depend on whether it is acute or chronic. Acute Glomerulonephri,s Risk Factors Recent Streptococcal Infec,on: Throat or skin infec-on with Streptococcus pyogenes (post-streptococcal glomerulonephri-s)【121:1†source】. Other Bacterial, Viral, or Parasi,c Infec,ons: Infec-ons such as Hepa,,s B, C, and malaria can trigger immune-mediated glomerulonephri-s【121:1†source】. Autoimmune Diseases: Condi-ons like Goodpasture syndrome and systemic lupus erythematosus (SLE) increase the risk of glomerulonephri-s【121:1†source】. Medica,ons & Toxins: Certain NSAIDs, an-bio-cs, and toxins increase risk【 121:1†source】. Vascular Disorders: Condi-ons like hypertension and vasculi,s can cause endothelial injury to the glomerulus【121:1†source】. Chronic Glomerulonephri,s Risk Factors  Diabetes Mellitus: Diabe,c nephropathy is a major risk factor for chronic glomerular injury【121:0†source】. Chronic Infec,ons: Prolonged infec-ons with viruses like Hepa,,s B, C can result in immune complex deposi-on and chronic glomerular injury【121:1†source】. Autoimmune Condi,ons: Chronic lupus (SLE) and rheumatoid arthri,s increase the risk of chronic glomerulonephri-s【121:1†source】. Family History: Gene-c predisposi-on to autoimmune diseases can increase risk【 121:1†source】. Summary Table Criteria Glomerulonephri,s Primary: Immunological responses (Type II, III, IV hypersensi-vity), infec-ons Most Likely (post-strep), toxins, medica-ons, ischemia. Secondary: Diabetes, lupus, Cause chronic infec-ons【121:1†source】. Immune complex deposi-on, an-body-mediated aCack, complement Pathophysiology ac-va-on, endothelial damage, capillary obstruc-on, glomerular permeability changes, and fibrosis【121:1†source】. Not transmissible. However, Streptococcus infec,ons that lead to post- Transmission streptococcal glomerulonephri-s are transmissible【121:1†source】. Acute: Recent strep infec-on, autoimmune diseases (Goodpasture, SLE), Risk Factors drugs/toxins, hypertension. Chronic: Diabetes, lupus, hepa--s B/C, chronic infec-ons, family history【121:1†source】. Nephro,c Syndrome Nephro-c syndrome is a kidney disorder characterized by massive protein loss (proteinuria), hypoalbuminemia, edema, and hyperlipidemia/hyperlipiduria. It results from damage to the glomerular filtra,on barrier, which increases permeability to proteins while maintaining the ability to restrict the movement of red blood cells【121:0†source】. 1. Most Likely Cause The causes of nephro-c syndrome can be classified as primary (idiopathic) or secondary. Primary Causes (Idiopathic) 1. Minimal Change Disease (MCD): o Most common in children. o Damage to podocytes leads to loss of the nega-ve charge on the glomerular basement membrane (GBM), allowing albumin to pass into the urine【 121:0†source】. 2. Focal Segmental Glomerulosclerosis (FSGS): o Sclerosis (scarring) of segments of some glomeruli. o O[en idiopathic but can be linked to HIV infec,on, obesity, and heroin use【 121:0†source】. 3. Membranous Nephropathy: o Caused by immune complex deposi-on on the glomerular basement membrane. o Associated with autoimmune diseases (like lupus), cancer, or certain infec,ons 【121:0†source】. Secondary Causes Diabe,c Nephropathy: Damage to glomerular capillaries caused by chronic hyperglycemia. Systemic Lupus Erythematosus (SLE): Autoimmune aCack on the kidneys. Infec,ons: Hepa--s B, Hepa--s C, HIV, and malaria. Medica,ons: Use of nonsteroidal an--inflammatory drugs (NSAIDs) or penicillamine. Amyloidosis: Deposi-on of amyloid proteins in the kidney【121:1†source】. 2. Pathophysiology The pathophysiology of nephro-c syndrome revolves around injury to the glomerular filtra,on membrane. The filtra-on membrane has three key components: 1. Fenestrated endothelium 2. Glomerular basement membrane (GBM) 3. Podocytes with foot processes (form filtra-on slits)【121:0†source】. Steps in Pathophysiology 1. Glomerular Injury: o Damage to any of the three filtra-on layers increases the permeability of the glomerular capillary wall to large proteins (like albumin)【121:0†source】. o Loss of the nega-ve charge on the GBM further increases protein leakage. 2. Massive Proteinuria:  o Massive proteinuria (≥ 3.5 g/day) occurs as proteins escape from the blood into the urine. o Albumin loss results in hypoalbuminemia, leading to decreased onco,c pressure in the blood【121:0†source】. 3. Edema Forma,on: o The decrease in onco-c pressure causes a shi[ of fluid from the vasculature into the inters--al space, resul-ng in generalized edema (anasarca)【121:0†source 】. o Compensatory ac-va-on of the renin-angiotensin-aldosterone system (RAAS) occurs, promo-ng sodium and water reten-on, further exacerba-ng edema【 121:0†source】. 4. Hyperlipidemia and Lipiduria: o Loss of proteins s-mulates hepa-c produc-on of lipoproteins, resul-ng in hyperlipidemia. o Some of these lipids also pass into the urine, causing lipiduria (presence of lipids in the urine)【121:0†source】. 5. Risk of Thrombosis: o Loss of an-coagulant proteins (like an-thrombin III) through the kidneys increases the risk of thrombosis (e.g., renal vein thrombosis)【121:0†source】. 3. Disease Transmission Transmission: o Not transmissible. Nephro-c syndrome is not an infec-ous disease. o Some of its secondary causes, such as HIV, hepa,,s B, and hepa,,s C, are transmissible. However, nephro-c syndrome itself is a non-communicable disease【121:0†source】. 4. Risk Factors Risk factors for nephro-c syndrome can be divided into modifiable and non-modifiable factors. Modifiable Risk Factors Infec,ons: HIV, hepa,,s B, hepa,,s C, and malaria infec-ons are linked to nephro-c syndrome【121:0†source】. Drug Use: o Intravenous drug use (increases risk of HIV and hepa--s C infec-ons). o Use of nephrotoxic drugs such as NSAIDs and an,bio,cs (like penicillamine) increases risk【121:0†source】. Obesity: Linked to focal segmental glomerulosclerosis (FSGS) due to increased glomerular capillary pressure【121:0†source】. Hypertension and Diabetes: Chronic hypertension and diabetes mellitus increase the risk of developing diabe-c nephropathy, which may present as nephro-c syndrome【 121:1†source】. Toxins: Exposure to certain heavy metals (like mercury) can cause nephro-c syndrome【 121:1†source】. Non-Modifiable Risk Factors Age: Minimal change disease (MCD) is the most common cause of nephro-c syndrome in children, while FSGS and membranous nephropathy are more common in adults【 121:1†source】. Gender: Certain types, like membranous nephropathy, are more common in men【 121:0†source】. Gene,cs: Gene-c muta-ons linked to FSGS and congenital nephro-c syndrome (e.g., muta-ons in NPHS1, NPHS2, or ACTN4 genes)【121:0†source】. Autoimmune Diseases: Diseases like systemic lupus erythematosus (SLE) are risk factors for developing nephro-c syndrome【121:0†source】. Summary Table Criteria Nephro,c Syndrome Primary Causes: Minimal change disease (children), FSGS, membranous Most Likely nephropathy. Secondary Causes: Diabetes, SLE, hepa--s B/C, infec-ons, Cause drugs, amyloidosis【121:0†source】. Glomerular filtra,on barrier injury → loss of nega,ve charge → massive Pathophysiology proteinuria → hypoalbuminemia → edema → RAAS ac,va,on → hyperlipidemia and lipiduria【121:0†source】. Not transmissible. However, infec-ons (HIV, hepa--s B/C) that cause Transmission nephro-c syndrome are transmissible【121:0†source】. Modifiable: Infec-ons (HIV, hepa--s B/C), drug use (NSAIDs, an-bio-cs), obesity, hypertension, diabetes, toxins. Non-Modifiable: Age (children for Risk Factors MCD, adults for FSGS), gene-cs, autoimmune diseases (like lupus), and gender【121:0†source】. Nephri,c Syndrome Nephri,c Syndrome is a type of glomerular disease characterized by hematuria (blood in urine), oliguria (reduced urine output), decreased glomerular filtra,on rate (GFR), and hypertension. It is o[en linked to immune-mediated injury of the glomerular capillaries, causing inflamma-on and disrup-on of the filtra-on barrier【121:0†source】. 1. Most Likely Cause The most likely causes of nephri-c syndrome include: Post-Streptococcal Glomerulonephri,s (PSGN): Occurs a[er infec-on with group A beta-hemoly,c Streptococcus. The infec-on may involve the skin (impe-go) or throat (pharyngi-s)【121:0†source】. Systemic Lupus Erythematosus (SLE): Autoimmune disorder where autoan,bodies form immune complexes that deposit in the glomerulus, leading to inflamma-on (Type III hypersensi-vity)【121:0†source】. IgA Nephropathy (Berger's Disease): Immune complexes containing IgA an,bodies are deposited in the glomerular mesangium, causing inflamma-on【121:0†source】. Goodpasture Syndrome: Autoan-bodies bind to type IV collagen in the glomerular basement membrane, leading to complement ac-va-on and glomerular damage【 121:0†source】. Other Causes: o Rapidly Progressive Glomerulonephri,s (RPGN): Can be caused by vasculi,s (e.g., ANCA-associated vasculi,s) or secondary to other condi-ons like SLE【 121:0†source】. o Henoch-Schönlein Purpura (HSP): Immune complex deposi-on (o[en with IgA) in the glomeruli【121:0†source】. 2. Pathophysiology The pathophysiology of nephri-c syndrome involves immune-mediated injury to the glomerular capillary wall, which results in an increase in permeability, glomerular inflamma-on, and reduced GFR. The main mechanisms include: 1. Immune Complex Deposi,on: o An,gen-an,body complexes get deposited in the glomerular capillary walls, par-cularly in cases of post-streptococcal glomerulonephri,s or SLE (Type III hypersensi-vity)【121:0†source】. o These immune complexes ac-vate the complement system, causing the recruitment of inflammatory cells (e.g., neutrophils)【121:0†source】. o The release of proteoly,c enzymes and reac,ve oxygen species (ROS) damages the glomerular endothelium, basement membrane, and podocytes, increasing the permeability of the filtra-on barrier【121:0†source】. 2. Direct An,body Binding: o In Goodpasture syndrome, autoan-bodies bind directly to type IV collagen in the basement membrane (Type II hypersensi-vity)【121:0†source】.  oThis ac-vates complement, promo-ng cell lysis and recruitment of immune cells, which cause further injury to the glomerular capillary【121:0†source】. 3. Damage to the Glomerular Filtra,on Barrier: o The injury to endothelial cells, basement membrane, and podocytes increases the permeability of the glomerular capillary, allowing red blood cells and proteins to pass into the urine【121:0†source】. o The result is hematuria (red blood cell casts) and mild proteinuria (less than seen in nephro-c syndrome)【121:0†source】. 4. Reduc,on in GFR: o Damage to the glomerular filtra-on barrier and capillary lumen increases pressure in the Bowman’s capsule, leading to reduced filtra-on rate【 121:0†source】. o The reduced GFR results in oliguria (low urine output), fluid reten-on, and hypertension【121:0†source】. 3. Disease Transmission Transmission: o Nephri-c syndrome itself is not a transmissible disease. o However, the underlying infec-ons (e.g., streptococcal pharyngi,s or impe,go) that trigger post-streptococcal glomerulonephri-s are contagious and can be transmiCed via respiratory droplets (pharyngi-s) or skin contact (impe-go)【 121:0†source】. o Goodpasture syndrome, SLE, and IgA nephropathy are not transmissible since they result from autoimmune or gene,c predisposi,ons【121:0†source】. 4. Risk Factors Risk factors for nephri-c syndrome vary depending on the specific cause. The following list includes both general and specific risk factors. General Risk Factors Infec,ons: History of recent streptococcal infec,on (skin or throat) increases the risk of post-streptococcal glomerulonephri,s【121:0†source】. Autoimmune Disorders: Systemic Lupus Erythematosus (SLE) is associated with immune complex deposi-on in glomeruli【121:0†source】. Age: Children are more likely to develop post-streptococcal glomerulonephri,s, while IgA nephropathy o[en affects young adults【121:0†source】. Family History: A family history of IgA nephropathy increases the risk of developing the condi-on【121:0†source】. Gene,c Factors: Muta-ons in genes involved in the immune response can predispose individuals to Goodpasture syndrome or IgA nephropathy【121:0†source】. Environmental Factors: Exposure to certain infec,ons (e.g., viral, bacterial), or toxic chemicals may increase risk【121:0†source】. Summary Table Criteria Nephri,c Syndrome Most Likely Post-Streptococcal Glomerulonephri,s, SLE, IgA nephropathy, Goodpasture Cause syndrome, Henoch-Schönlein Purpura【121:0†source】. Immune injury to glomerular filtra,on barrier → Inflamma,on → Loss of Pathophysiology endothelial integrity → RBCs and proteins leak into urine → Hematuria, oliguria, hypertension【121:0†source】. Not transmissible, but infec-ons (e.g., streptococcal pharyngi-s) that trigger Transmission nephri-c syndrome are transmissible via respiratory droplets or skin contact 【121:0†source】. Infec,ons (streptococcal infec-ons), autoimmune diseases (SLE), age (children for PSGN, adults for IgA nephropathy), family history (IgA Risk Factors nephropathy), and gene,c factors (autoimmune disorders)【121:0†source】. Clinical Manifesta,ons Hematuria: Presence of red blood cell casts in the urine, o[en giving it a brown or "cola- colored" appearance【121:0†source】. Oliguria: Reduced urine output due to decreased GFR【121:0†source】. Hypertension: Due to fluid reten-on from reduced kidney filtra-on【121:0†source】. Edema: Swelling of the face or extremi-es may occur in severe cases【121:0†source】. Proteinuria: Although protein is present in the urine, it is typically less severe than in nephro,c syndrome【121:0†source】.