Amyloidosis PDF

AMYLOIDOSIS  Amyloid Deposition: Misfolded proteins that accumulate as insoluble fibrils in tissues.  Amyloid is an abnormal, extracellular protein material composed of misfolded protein fibrils that aggregate and deposit in tissues, causing structural disruption and organ dysfunction Amyl...

AMYLOIDOSIS  Amyloid Deposition: Misfolded proteins that accumulate as insoluble fibrils in tissues.  Amyloid is an abnormal, extracellular protein material composed of misfolded protein fibrils that aggregate and deposit in tissues, causing structural disruption and organ dysfunction Amyloidosis  Definition: Deposition of pathologic proteinaceous substance between the cells (extra cellular).  The name amyloidosis is derived from the similarity of staining amyloid " substance with iodine to that of starch (Amylon = starch in Greek)  When iodine is added to a fresh specimen containing amyloid a brown colouration is developed, that turns to bluish violet when sulphuric acid is added.  Histologically:  amyloid can be stained by:  H & E: It appears as a homogeneous, eosinophilic structureless extracellular material.  Congo red: Appears pink or red by light microscope  A green birefringeness is seen by polarized light. Liver amyloidosis Chemical nature of amyloid deposits:  Approximately, 95% of amyloid deposits are made up of fibrillar proteins. The remaining 5% are glycoproteins.  Two chemically distinct major classes of amyloid fibrillar proteins have been identified.  Amyloid light chain (AL): It is derived from plasma cells (immimocytes) and contains Ig light chains.  Amyloid associated (AA): is a non immunoglobulin protein synthesised by the liver.  Other proteins are:  Transthyretin (TTR) serum protein synthesized by liver &transport Thyroxine and retinol  AB2-macroglobulin : In prolonged dialysis  B-amyloid proteins: in Alzheimers disease  Prion protein (APrP) Non-fibrillar amyloid protein  1- Amyloid P component-found in all forms of amyloid  2- Apolipoprotein-E (apoE)  3-Sulfated glycosaminenoglycans (GAGs) Classification 1-Generalized systemic amyloidosis: a) Primary systemic amyloidosis b) Secondary systemic amyloidosis c) Hemodialysis associated amyloidosis d) Heredofamilial 2- Localized amyloidosis: a) Localized organ amyloidosis b) Endocrine amyloidosis c) Aging Primary systemic amyloidosis:  The distribution is found mainly in the heart, kidney, G.I.T, peripheral nerves, skin and tongue.  The amyloid deposit is that of AL.  It is seen in 5-15% of patients with plasma cell myeloma or B-cell lymphoma.  It is also seen in many patients without overt B-cell lymphoma but they have monoclonal Iga and /or light chains.  Pathogenesis: This is due to excessive Ig production particularly light chain with defective degradation leading to formation of amyloidogenic protein (AL): Secondary (reactive) systemic amyloidosis:  The distribution is found mainly in kidneys, liver, spleen, L.Ns, adrenals and thyroid.  The amyloid deposit is AA.  It is seen in chronic inflammatory states as:  Pyogenic infections: abscess, bronchiectasis or chronic suppurative osteomyelitis.  Rheumatoid arthritis and other connective tissue disorders such as ankylosing spondylitis  Granulomatous disease as tuberculosis, and leprosy.  Inflammatory bowel diseases (IBD).  Some neoplasms as Hodgkin's lymphoma (H.D) and renal cell carcinoma  Pathogenesis: long standing tissue destruction and inflammation leads to increased serum level of amyloid associated protein (SAA), SAA is synthesized in the liver under the effect of cytokines and is degraded by the action of monocyte-derived enzymes.  Increased serum level alone is not sufficient to produce amyloidosis but; if there is enzyme defect, it will lead to incomplete breakdown of SAA, generating insoluble AA molecules  o Hereditary Amyloidosis: Includes familial amyloid polyneuropathy, caused by genetic mutations in the transthyretin protein.  o Localized Amyloidosis: In Alzheimer’s disease, beta-amyloid plaques accumulate in the brain and contribute to neurodegeneration Morphology  Spleen:  Grossly : Is enlarged, firm, pale grey and waxy.  Microscopically :  Amyloid may be deposited  in follicles (Sago spleen)  in sinusoids and in connective tissue of the red pulp (Lordaceous spleen)  both.  Liver:  Gross :  Is enlarged, firm, pale grey and waxy.  Microscopy:  Amyloid is deposited on the wall of the sinusoides, gradually encroaching on parenchyma leading to pressure atrophy with massive hepatic replacement. Liver amyloidosis, iodine stain wall of sinusoids → pressure atrophy & hepatomegaly: pale, waxy, gray Diagnosis: 1- Renal, rectal, gingival, abdominal fat [congo red] 2- serum & urine electrophoresis Prognosis: ❖ Poor prognosis in multiple myeloma and systemic amyloidosis ❖ Better outcome in secondary amyloidosis if the cause is removed eg. Inflammation. Gangrene  Gangrene means necrosis with superadded putrefaction.  Necrotic tissue protein →putrefying bacteria →H2S →bad odor  H2s+ iron → iron sulphide (black colour) Types  Dry gangrene  Wet gangrene  Gas gangrene Dry gangrene  Exposed parts: extremities; upper and lower limbs  Complete occlusion of arterial supply with no collaterals  Veins and lymphatics are intact  Source of infection: exogenous from the environment as soil Morphology  The gangrene starts at the tip of fingers  The affected part is black with bad odour and mummified due to fluid loss by: 1-evaporation 2-venous and lymphatic drainage  There is a line of demarcation (red zone of inflammation) between healthy and necrotic tissue  There is a line of separation: deep groove towards the gangrenous part formed of suppurative granulation tissue.  Slow spread  Less toxemia Dry gangrene Moist gangrene  Internal organs as intestine, less commonly in exposed tissues as diabetic foot gangrene  Complete occlusion of arterial supply preceded by venous or lymphatic occlusion  Source of infection: endogenous from intestinal flora Morphology  The affected part is black, with bad odour and swollen (no evaporation and no venous or lymphatic drainage)  No line of demarcation or separation  Rapid spread of gangrene  More toxemia volvulus Strangulated hernia Diabetic foot gangrene  It starts as dry gangrene then becomes wet due to:  Hyperglycemia makes tissue swollen due to hyper- osmolarity of tissue  Hyperglycemia increases susceptibility to infection  Diseased blood vessels in diabetic Bed sores  Wet gangrene occurs in the skin of bedridden patients and appears as deep ulcers over bony prominence due to compression of blood vessels by bed mattress and bone with superadded infection from the environment. Cancrum oris  Wet gangrene seen around the mouth in debilitating child suffering from measles Gas gangrene  A type of wet gangrene occuring in massively crushed tissue as street accident  It is caused by clostridia  It is characterized by excess gas production giving crepitant tissue  Rapid spread of gangrene with severe toxemia and septicemia