PBL. Case 3. Day 2. 1 PBL – CASE 3. Skin rash, joint pain, oliguria, hematuria and proteinuria systemic inflammatory disorders, lupus nephritis. Day 2. Immunofluorescence. memory cards https://quizlet.com/_6k66ze ANCA glomerulonephritis and vasculitis https://cjasn.asnjournals.org/content/12/10/1680 https://www.researchgate.net/figure/Renal-biopsy-findings-a-Fibrocellular-crescentfibro cellular crescend occupies-Bowmans-space-with-focal_fig1_6759326 Definitions Sclerosis is the stiffening of a structure, usually caused by a replacement of the normal organspecific tissue with connective tissue. Cellular glomerular crescents are defined as two or more layers of proliferating cells in Bowman's space and are a hallmark of inflammatory glomerulonephritis and a histologic marker of severe glomerular injury. Fibro Cellular Crescend Nephritic Syndrome – hematuria (RBC casts), hypertension, azotemia, oliguria, proteinuria (<3.5 g/day). It refers to glomerular inflammationa and bleeding. Nephrotic Syndrome – severe proteinuria (>3.5 g/day), hypoalbuminemia (<3 g/dL), generalized edema, hyperlipidemia, lipiduria.It is caused by glomerular damage. Other symptoms may include weight gain, feeling tired, and foamy urine. USMLE STEP 1. Lecture notes. Pathology. Chapter 1. Microscopic examination of tissue is conducted with 1. Histochemical stains: In light microscopica examination of tissue, hematoxylin and eosin (H&E) is considered the gold standard stain. hematoxylin (blue to purple) binds with nucleic acids and calcium salts, that are allocated in nuclei, nucleoli, bacteria, calcium storages; eosin (pink to red) binds the majority proteins, both extracellular and intracellular (cytoplasm, collagen, fibrin, RBC, thyroid colloid) Other histochemical stains prussian blue stains iron congo red stains amyloid acid fast acid-fast bacilli periodic acid-Schiff (PAS) stains high carbohydrate content molecules (glycoproteins and proteoglycans) Gram stain stains bacteria trichrome stains cells and connective tissue reticulum Stains collagen type III molecules 2. Immunohistochemical (antibody) stains: cytokeratin vimentin desmin prostate specific antigen Many others Ancillary techniques include 1. immunofluorescence microscopy (IFM), which is typically used for renal and autoimmune disease 2. transmission electrone microscopy (EM), used for renal disease, neoplasms, infections and genetic disorders PBL. Case 3. Day 2. 2 USMLE STEP 1. Lecture notes. Pathology. Chapter 15. Hyperlipidaemia in nephrotic syndrome is caused by 2 factors. 1. Hypoproteinemia stimulates protein synthesis in the liver, resulting in the overproduction of lipoproteins. 2. Lipid catabolism is decreased due to lower levels of lipoprotein lipase, the main enzyme involved in lipoprotein breakdown. Cofactors, such as apolipoprotein C2 may also be lost by increased filtration of proteins. Renal biopsy can yield a defiinte diagnosis when light microscopy features are considered in concert with immunofluorescence (IF) and electron microscopy (EM). PRIMARY GLOMERULOPATHIES (NEPHRITIC SYNDROME) 1. Acure poststeptococcal glomerulonephritis (APSGN) 2. Rapibly progressive glomerulonephritis (RPGN) (crescentis glomerulonephritis) – is a group of disease characterized by glomerular crescent and a rapid deterioration of renal function. Pulmonary involvement (pulmonary hemorrhage and hemoptysis) is called Goodpasture syndrome. 2.1 Anti-glomerular basement membrane antibody-mediated crescentic glomerulonephritis It has a peak incidence at age of 20-40, and males are affected more frequently than females. Renal biopsy findings include hypercellularity, crescents, and fibrin deposition in glomeruli. IF shows a smooth and liner oattern of IgG a and C3 in the gromerular basement membrane. By EM , there are no deposits, but there is glomerular basement membrane disruption. 2.2 Immune-complex mediated crescentic glomerulonephritis Any of the immune complex nephritides can cause crescent formation IF showes a granular pattern and EM shows discrete deposits. 2.3 Pauci-immune crescentic glomerulonephritis Antineutrophilic cytoplasmic antibodis (ANCA) are present in serum. IF and EM are negative for immunoglobulins and complement components. 3. Membranoproliferative glomerulonephritis (MPGN) affects both the glomerular measngium and the basement membrane, MPGN may be secondary to many systematic disorders (systemic lupus erythematosus, endocarditis), chronique infections (HIV, HCV, HIV) and malignancies (chronic lymphocytic leukemia). 4. Alport syndrome is characterized by hereditary nephritis, hearing loss and ocular abnormalities. The most common mutation is in the gene, coding type IМ collagene. SECONDARY GLOMERULONEPHRITIS It is secondary to other disease processes. Diabetes causes nodular glomerulosclerosis (Kimmelstiel-Wilson Syndrome), hyaline arteriosclerosis and diabetic microangiopathy. Systematic lupus erythematosus can cause various patterns of damage to the kidney with clinical features that can include hematuria, nephritic syndrome, nephrotic syndrome, hypertension and renal failure. PBL. Case 3. Day 2. 3 Definitions Vasculitis is a group of disorders that destroy blood vessels by inflammation. Both arteries and veins are affected. Lymphangitis is sometimes considered a type of vasculitis. Vasculitis is primarily caused by leukocyte migration and resultant damage. Pauci-immune vasculitis is a form of vasculitis that is associated with minimal evidence of hypersensitivity upon immunofluorescent staining for IgG. Microscopic polyangiitis (MPA) is an ill-defined autoimmune disease characterized by a systemic, pauci-immune, necrotizing, small-vessel vasculitis without clinical or pathological evidence of necrotizing granulomatous inflammation. What is microscopic polyangiitis (MPA)? What is vasculitis? USMLE STEP 1. Lecture notes. Pathology. Chapter 12. There are three conditions which are grouped together under the umbrella term ‘ANCA-associated vasculitis’ because they are all associated with a key protein factor in the blood called ‘ANCA’ and because they all cause inflammation or damage to small blood vessels, most commonly in the kidneys, lungs, joints, ears, nose, and nerves: 1. GPA (granulomatosis with polyangiitis) – Wegener’s granulomatosis, 2. EGPA (eosinophilic granulomatosis with polyangiitis) - Churg-Strauss syndrome (1). 3. those that are mediated by immune complexes (e.g., anti-glomerular membrane disease) also known as Henoch-Schonlein purpura. PBL. Case 3. Day 2. 4 USMLE STEP 1. Lecture notes. Immunology and microbiology. Chapter 7.