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Mechanisms of Viral Injury 1. Viral Tropism (Tissue and Cell Specificity) Host receptors for viruses Viruses are coated with surface proteins that bind with high specificity to particular host cell surface proteins. Entry of many viruses into cells commences with binding to normal host cell receptors. For example, HIV glycoprotein gp120 binds to CD4 and CXCR4 and CCR5 on T cells and macrophages. Host proteases may be needed to enable binding of the virus to host cells; for instance, a host protease cleaves and activates the influenza virus hemagglutinin. Specificity of transcription factors The ability of the virus to replicate inside particular cell types depends on the presence of lineage-specific transcription factors that recognize viral enhancer and promoter elements. For example, the JC virus, which causes leukoencephalopathy, replicates only in oligodendroglia in the CNS because the promoter and enhancer DNA sequences regulating viral gene expression are active in glial c...

 Von Willebrand disease Von Willebrand disease (VWD) is the most common inherited bleeding disorder. It occurs due to a deficiency or dysfunction of von Willebrand factor (vWF) — a protein that plays a critical role in blood clotting. Causes of Von Willebrand Disease Von Willebrand disease is primarily a genetic disorder , meaning it is usually inherited from one or both parents. The condition occurs when there is a deficiency or abnormal function of von Willebrand factor (vWF) , a protein that helps blood clot properly. This protein plays a key role in the initial stages of blood clotting by helping platelets stick to the walls of damaged blood vessels and stabilizing factor VIII, another important clotting protein. The most common form of the disease, Type 1 , is caused by a partial deficiency of vWF and is typically inherited in an autosomal dominant pattern , which means only one copy of the altered gene is enough to cause the disorder. Type 2 results from structural or func...

 Granulomatosis With Polyangiitis Previously called Wegener granulomatosis, granulomatosis with polyangiitis (GPA) is a necrotizing vasculitis charac-terized by a triad of the following: Necrotizing granulomas of the upper-respiratory tract (ear, nose, sinuses, throat) or the lower-respiratory tract (lung) or both Necrotizing or granulomatous vasculitis affecting small-to medium-sized vessels (e.g., capillaries, venules, arteri-oles, and arteries), most prominently the lungs and upper airways but other sites as well Focal necrotizing , often crescentic, glomerulonephritis.   "Limited" forms of disease can be restricted to the respi ratory tract. Conversely, when widespread the disease may affect the eyes, skin, and other organs, most notably the heart; clinically, widespread GPA resembles PAN with the additional feature of respiratory involvement. GPA is likely initiated as a cell-mediated hypersensitivity response to inhaled infectious or envirorimental antigens. PR3-ANCA...

 Polyarteritis Nodosa Polyarteritis nodosa (PAN) is a systemic vasculitis of small- or medium-sized muscular arteries; it typically involves the renal and visceral vessels and spares the pulmonary circulation. There is no association with ANCAS , but one-third of patients have chronic hepatitis B infection, which leads to the formation of immune complexes containing hepatitis B antigens that deposit in affected vessels. The cause is unknown in the remaining cases. Pathogenesis of PAN Immune complex–mediated vasculitis , often linked to Hepatitis B . Immune complexes deposit in medium-sized arteries. Activate the complement  system → recruit neutrophils . Causes fibrinoid necrosis and inflammation of the vessel wall. Leads to thrombosis , aneurysms , and organ ischemia . Not associated with ANCA . Morphology of PAN Classic PAN is a segmental transmural necrotizing inflammation of small- to medium-sized arteries, often with superimposed thrombosis. Kidne...

 Microscopic Polyangiitis Microscopic polyangiitis is a necrotizing vasculitis that generally affects capillaries, as well as small arterioles and venules. It also is called hypersensitivity vasculitis or leukocytoclastic vasculitis. Unlike in PAN (polyarteritis nodosa) , all lesions of microscopic polyangiitis tend to be of the same age in any given patient. The skin, mucous membranes, lungs, brain, heart, gastrointestinal tract, kidneys, and muscle all can be involved; necrotizing glomerulonephritis (seen in 90% of patients) and pulmonary capillaritis are particularly common Microscopic angiitis can be a feature of a number of immune disorders, such as Henoch-Schönlein purpura, essential mixed cryoglobulinemia, or the vasculitis associated with connective tissue disorders. In some cases, antibody responses to antigens such as drugs (e.g., penicillin), microorganisms (e.g., streptococci) , heterologous proteins, or tumor proteins have been implicated. These reactions can eithe...

 Kawasaki Disease Kawasaki disease is an acute, febrile, usually self-limited illness of infancy and childhood associated with an arteritis of mainly large- to medium-sized vessels. Approximately 80% of patients are younger than 4 years of age. Its clinical significance stems from the involvement of coronary arteries. Coronary arteritis can result in aneurysms that rupture or thrombose, causing myocardial infarction. Originally described in Japan, the disease is now recognized in the United States and elsewhere. In genetically susceptible individuals, a variety of infectious agents (mostly viral) have been posited to trigger the disease. The vasculitis may result from a delayed-type hypersensitivity response directed against cross-reactive or newly uncovered vascular antigen(s). Subsequent cytokine production and polyclonal B cell activation result in auto-antibodies to ECs and SMCs that precipitate the vasculitis. Morphology of Kawasaki disease Affects medium-sized arteries , es...

CLINICAL EXAMINATION OF SENSORY SYSTEM During examination of the sensory system, test various types of sensations.  Peripheral nervous system functions (PNSF) 1. Tactile sensibility 2 Pain 3. Temperature 4. Sense of position 5 Vibrations 6. Presence of any abnormal sensation Cortical sensory functions: 1. Point localization 2. Two point discrimination 3. Recognition of size, weight, shapes and form of objects (Sterorignotis) 4 Graph aesthesia 5. Extinction phenomenon Before starting the examination, introduce yourself and explain the nature of the test to be performed to the patient to get his full cooperation. The eyes should then be closed, and the test should elicit different forms of sensations. Always compare corresponding points on both sides of the body It routinely involves assessing the sensation of the hands, lower arms, abdomen, feet, and lower legs. Facial sensation is tested during the evaluation of cranial nerves PRINCIPLES OF SENSORY ASSESSMENT: The sensations are ev...