Myopathies PDF

# Myopathies ## Nuclear Abnormalities - **Karyolysis** - the disappearance of nuclei due to complete dissolution of DNA - **Pyknosis** - condensation of chromatin leading to shrinkage of the nuclei - **Karyorrhexis** - Fragmentations of nuclei preceded by pyknosis ## Mitochondria: - **Muscle we...

# Myopathies ## Nuclear Abnormalities - **Karyolysis** - the disappearance of nuclei due to complete dissolution of DNA - **Pyknosis** - condensation of chromatin leading to shrinkage of the nuclei - **Karyorrhexis** - Fragmentations of nuclei preceded by pyknosis ## Mitochondria: - **Muscle weakness** - Particularly affecting the extra ocular muscles - **Degenerative disease** - Affects the CNS - loss of optic nerve degeneration of brain white matter - loss of cerebellar tissue - **Metabolic Disturbance** - Accumulation of high levels of lactic acid - **MELAS** - Characterized by mitochondrial encephalomyopathy lactic acidosis, recurring stroke like episodes, muscle weakness & tonic clonic seizures - **MERRF** - Characterized by myoclonic epilepsy with ragged red fibers, destruction of important proteins involved in oxidative phosphorylation & generalized seizures ## Peroxisomal: - **Zellweger syndrome** - Is a genetic disease in which normal peroxisomes are absent. Infants with this syndrome have profound neurological disorders and liver and kidney problems. - **Adreno leukodystrophy** - Is caused by inability of peroxisomes to metabolize fatty acids. Therefore, lipids accumulate in nervous system and adrenal glands impairing their function ## Proteasomes: - **Alzheimer’s disease** - **Huntington’s disease** - Are two neurological disorders caused by accumulation of protein inside the cells due to failure of degradation by proteasomes ## Neurological Disorders - **Alzheimer Disease** - Common type of dementia in elderly affects the perikaryon and synapse within the cerebrum - **Neurofibrillary tangles** - Which are accumulation of tau proteins and microtubules - **Neuritic plaques** - Which are dense aggregate of B-amyloid protein - **Huntington Chorea** - The cause is loss of basal ganglia neurons that produce the neurotransmitter A-aminobutyric acid [GABA] - **Parkinson’s Disease** - The cause is the loss of dopaminergic neurons from the substantia nigra from the brain. ## Guillain-Barré Syndrome - An autoimmune disorder of the PNS by bacterial or viral infection - **Symptoms:** - Ascending weakness - Flaccid paralysis of limbs - Diminished tendon reflexes - Autonomic dysfunction - **Histopathology:** - Lymphocytic [mostly T cell] - Infiltration of endoneurium of peripheral nerves - Macrophage - mediated segmented demylination of nerve fibers - **EM:** Macrophages are seen penetrating Schwann Cell basal laminae near nodes of ranvier ## Multiple Sclerosis [MS] - Is a chronic inflammatory disease of the CNS characterized by loss of myelin; damaged patches called plaques appear in different areas of white matter - unpredictable disease - **MS activity:** Leukocytes [T cells] are drawn to the regions of the white matter which initiates inflammatory response accompanied by loss of oligodendrocytes and axon demylination - **Etiology of disease:** - Viral - Autoimmune ## Epithelial Disorders - **Celiac disease:** Also called gluten-sensitive enteropathy or sprue - Damage the small intestine - loss of microvilli - **Kartagner’s Syndrome:** Characterized by absence or dysmotile cilia caused by defect of microtubules. - **Bladder Metaplasia:** The bladder is normally lined up by transitional epithelium - Chronic irritation of the bladder wall - Schistosoma infection indwelling catheters - Urinary Calculi - Change transitional to squamous epithelium - **Barret epithelium:** In cases of chronic acid reflux from the stomach into the lower esophagus the stratified squamous non keratinized epithelium of esophagus is replaced to mucus secreting epithelium, like in stomach. - Precursors for oesophageal adenocarcinoma - **Carcinomas** - Are malignant tumors that arise from surface epithelium - **Adenocarcinomas** - Are malignant tumors that arise from glandular epithelium. ## Connective Tissue - **Fibrosis:** Tissue injury in organs heart, lung, or kidney may activate the fibroblast to form collagen scar [Fibrosis] - The fibrotic scar differs from normal tissues and may obliterate normal tissues leading to dysfunction and organ failure - **Plasma Cells:** - **Multiple Myeloma:** Abnormal plasma cells called myeloma cells accumulate in bone marrow - activation of osteoclast [bone cell that breaks bone tissue] - Leads to: Painful lytic lesions and consequent hypercalcemia [high calcium levels] - Also causes: Suppression of hematopoiesis - thrombocytopenia anemia leukopenia - **Myeloma nephropathy:** Due to overproduction of immunoglobin which manifest with increased serum creatinine and hematuria ['blood in urine] ## Anaphylaxis - Life threatening allergic reaction - IgE antibodies bind with allergens - Mast cells contain IgE receptors - IgE receptors + antigens = Mast cell releasing granules. - Histamines dilate small blood vessels and increase their microvasculature, so that plasma leaks. - Skin appear red [wheals] - Edematous [urticaria] be caused by Penicillins and cephalosporins. - This could lead to severe hypotension, mucosal edema of respiratory tract that can cause suffocation - lead to death ## Connective Tissue Fibers - **Marfan Syndrome:** Genetic disease caused by absence of fibrillin. - Tall stature with very wide arm span - Recurrent subluxation of eye lens - Aortic aneurysm [dilatation of aorta] - **Lung emphysema:** Deficiency of a1-antitrypsin leads to dilated bronchi - inhibitor of elastase ## Lysosome: - **Hurler’s syndrome** - **Tay-Sachs** - **Gaucher** ## Hurler Syndrome - Caused by deficiency of lysosomal enzyme, IUDA, which aid in the break down of dermatan sulfate and heparin sulfate [GAG] - Lead to death - Physical damage - Mental damage - **Hunter Syndrome:** Rare, inherited disorder in which the body doesn’t properly digest [break down] sugar molecules [Mucopolysaccharide] in the body. ## Autoimmune disorder - Systemic lupus erythematosus - Rheumatoid arthritis ## Inherited Disorder - Ehlers Danlos Syndrome - Marfan Syndrome - Osteogenesis imperfecta - Alport syndrome ## Alport syndrome - A genetic condition characterized by kidney disease, loss of hearing and eye abnormalities - Caused by an abnormality of a gene that codes for type [IV] collagen