FARMACO 1. Definiciones en farmacología, transporte celular, receptore
1 AlteracióN Celular
Transcript of 1 AlteracióN Celular
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TRASTORNOS METABÓLICOS GENERALES.
ACUMULACIONES Y DEPÓSITOS INTRA Y EXTRACELULARES.
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Fluid mosaic model of cell membrane structure. The lipid bilayer provides the basic structure and serves as a relatively impermeable barrier to most water-soluble molecules.
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Functions of transmembrane proteins. A variety of functions are performed by different types of cell membranes as shown.
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Membrane systems. The rough endoplasmic reticulum and Golgi apparatus are important organelles in cellular biosynthesis of proteins and glycoproteins inserted into cell membranes and used in and secreted from cells. Transcription, translation, assembly, modification, and packaging of these molecules occur in an orderly sequence from the nucleus to the cell membrane as shown. Alterations in one or more of these steps can result in cell injury and serve as the underlying pathogenesis of a disease process.
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The complexity of and interrelations between intermediate filaments, microtubules, endoplasmic reticulum, and other cytoplasmic organelles that can be involved in the pathogenesis of diseases are shown.
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Una de las manifestaciones celulares de los trastornos metabólicoses el acumulo de cantidades anormales de diferentes substancias:
1. Sustancia endógena. Agua, lípidos, proteínas o carbohidratos.
2. Sustancias del metabolismo anormal o exógenas que se depositan a nivel intra y extracelular.
3. Sustancia exógena que se deposita y acumula debido a que no puede ser degradada por las células.
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DEGENERACIÓN (Distrofia = nutrición deficiente)Abarca lesiones reversibles e irreversibles a nivel
intra y extracelular
Cada forma de degeneración responde a un trastorno metabólico, cuyosmetabolitos o estructuras especiales experimentan un aumento, uncambio o una alteración.
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Stages in the cellular response to stress and injurious stimuli.
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Representación esquemática de las alteraciones reversibles e irreversibles producidas por hipoxia (Modificado de Wyllie AH en Cell death in biology and pathology. Chapman & Hall, Londres, 1981).
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Alteraciones del Metabolismo Hídrico • Cambio hidrópico u oncosis• Edema Celular• Acumulación Intracelular de Agua
Tumefacción turbia >> reversible Degeneración vacuolar >> irreversible Degeneración hidrópica >> irreversible
Alteraciones del Metabolismo Lipídico• Lipidosis (cambio graso) >> reversible/ irreversible
Alteraciones del Metabolismo Proteico• Degeneración hialina >> reversible/ irreversible• Depósitos hialinos intra y extracelulares
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Acumulación de Agua.
Cambio Hidrópico
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H2OH2O
> glucose
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( Cell death / point of no return)
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The process of acute cell swelling (hydropic degeneration).
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Cambio o Degeneración Hidrópica
normal
Edema celular
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Lumen
Núcleo
Lumen
Núcleo
Túbulo renal normal Túbulo renal con edema
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Estómago
mucosa edematosa
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Intestino delgado(intususcepción)
mucosa edematosa
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Hígado
Acute cell swelling, liver, mouse. Hepatic swelling in a mouse exposed to chloroform 24 hours previously. The accentuated lobular pattern and slight pallor in the liver on the left are the result of acute cell swelling (hydropic degeneration) and necrosis of centrilobular hepatocytes. The right liver is normal.
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Liver from a mouse with chloroform toxicosis. While many hepatocytes in the centrilobular areas (at right) are necrotic, several cells at the interface of normal and necrotic (arrows) are still undergoing acute cell swelling (hydropic degeneration).
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Ballooning degeneration, papular stomatitis, oral mucosa, cow. Cells infected by some types of virus, such as papular stomatitis virus, are unable to regulate their volume and swell at certain stages of the infection. These cells may become very large (ballooning degeneration) and eventually rupture. Some of the cells have viral inclusion bodies (arrows). H&E stain.
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Acumulación de Lípidos.
Cambio Graso
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Trastorno del Metabolismo de los Lípidos
Degeneración grasa, cambio graso, lipidosis, infiltración grasa, esteatosis celular:
• Acumulación intracelular excesiva de lípidos (triglicéridos) en tejidos no adiposos.
• Observado más frecuentemente en miocardio, hígado, epitelio tubular renal.
Causas: Dieta rica en grasas Caquexia Hipoxia Anoxia Tóxicos (tetracloruro de carbono, fósforo, tetraciclinas)
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Metabolismo de los Lípidos
el hígado en el transporte y almacenamiento de lípidos
• Facilita la digestión y absorción de lípidos mediante la formación de bilis (bilis y colesterol).
• Tiene sistemas enzimáticos para sintetizar triglicéridos.
• Convierte los ácidos grasos en cuerpos cetónicos.
• Desempeña una función integral durante la síntesis y metabolismo de lipoproteínas.
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Metabolismo de los Lípidos
1
2
3
4
5to thoracicduct
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LIPOPROTEIN LIPASE:• adipose tissue
• mammary gland• cardiac muscle• skeletal muscle
Lipid Absorption and Storage
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fatty_acid_metabolism[1].swf
Metabolismo de los LípidosMetabolismo de los Triglicéridos >> generalidades
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Metabolismo de los Lípidos
Ácidos grasos libres(AGL o quilomicrones)
AGL
1
Triglicéridos
Metabolismo•Ésteres del colesterol• Fosfolípidos• Oxidación a cetonas, CO2
2
Acetato
-glicerofosfato
3
Lipoproteínas
Apoproteína
4
5
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lipoproteins[1].swf
Metabolismo de los Lípidos
funciones de las lipoproteínas
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Causas de Hígado Graso
Ácidos grasos libres(AGL)
AGL
1
Triglicéridos
• Ésteres del colesterol• Fosfolípidos• Oxidación a cetonas, CO2
2
Acetato
-glicerofosfato
3
Lipoproteínas
Apoproteína
4
5
• Sobrealimentación• Desnutrición
O2
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Formas Intracelulares de Adiposis
a. Gotas finas b. Gotas finas y gruesas c. Células con forma de anillo
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Steatosis (fatty liver, fatty change, hepatic lipidosis), liver, ox. In this severely affected liver, all hepatocytes are vacuolated and their nuclei have been displaced to the side. H&E stain.
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Esteatosis Hepática
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COBALT DEFICIENCY, PRESUMPTIVE
normalliver esteatosis
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COBALT DEFICIENCY, PRESUMPTIVE
PHOTOSENSITIZING SKIN DISEASE
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COBALT DEFICIENCY, PRESUMPTIVE
PHOTOSENSITIZING SKIN DISEASE
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Fatty ChangeKidney
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Macrófagos ingiriendo lípidos.Moquillo canino
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HYPERCHOLESTEROLEMIA DUE TO 4% CHOLESTEROL DIET, EXPERIMENTAL
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Aurora borealis (Northern Lights)
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Nube Iridiscente
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Acumulación de Glucógeno
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Metabolismo de los Carbohidratosglucógeno
Las células no pueden almacenar grandes cantidades de moléculasde glucosa, porque una abundancia de éstas ejercería una tremendapresión osmótica que ocasionaría la entrada masiva de agua a lacélula.
En su lugar, muchos órganos como el hígado, músculo esqueléticoy cardíaco almacenan a este carbohidrato como glucógeno.
La formación de glucógeno a partir de glucosa se denominaglucogénesis. El proceso contrario se denomina glucogenólisis.
Tanto la glucólisis como la glucogenólisis están controlados porlas hormonas insulina, glucagon y epinefrina, y por las enzimas glucógenofosforilasa y glucógeno sintasa.
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Metabolismo de los Carbohidratosglucógeno y otros polisacáridos
(1→4)
(1→6)
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Metabolismo de los Carbohidratosglucógeno (anabolismo y catabolismo)
cell cytoplasm
glycogenesis
glycogenolysis
phosphoglucomutase
hepatocyteskeletal muscle
insulinglucagon
UDP-glucose
UTP
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Acumulación de Glucógeno
El glucógeno es la forma normal de almacenamiento de glucosa (dextrosa) en las células (hepáticas y musculares).
• Hiperglucemia de cualquier causa (Diabetes mellitus).
• Trastornos metabólicos inducidos por drogas (corticosteroides).
• Deficiencias enzimáticas.
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Metabolismo del Glucógeno
Glucosa
Glucosa
Glucógeno
Glucosa
1
2
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Glucocorticoid hepatopathy, liver, dog. Extensive accumulation of glycogen in hepatocytes leads to an enlarged and pale brown to beige liver in dogs with glucocorticoid excess from endogenous (Cushing’s disease) or exogenous sources. The liver is usually enlarged and the edges rounded. This cut surface would bulge on incision and not be greasy.
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Glucocorticoid hepatopathy, liver, dog. Note the swollen hepatocytes (arrows) with extensive cytoplasmic vacuolation. H&E stain.
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Acumulación de Proteínas
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Alteraciones del Metabolismo Proteico
• Degeneración hialina >> reversible/irreversible.
• Depósitos hialinos intra y extracelulares.
Hialina (Hyalos = Vidrio)
• Cualquier depósito, acumulación o desintegración de proteínas intra / extracelulares.
• Depósitos homogéneos y transparentes.
• Depósitos eosinófilos sin estructura definida al microscopio de luz.
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Hialinas Intracelulares
Observadas regularmente en el citoplasma de células glandulares o en células con alta producción de proteínas.
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Hígado Riñón
Corpúsculos de Mallory
Lumen
Hialinas Intracelulares
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Cell droplets and inclusion bodies. Resorption droplets, proteinuria, kidney, dog. The cytoplasm of the proximal tubule epithelial cells are filled with eosinophilic homogeneous droplets—protein that has been resorbed by the cells from the glomerular filtrate. H&E stain.
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Hialinas Intracelulares
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NúcleoNúcleo
Ac
RERRERdilatadodilatado
Corpúsculos de Russel
Hialinas Intracelulares
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Hialinas extracelulares
Afectan las fibras colágenas, las membranas basales de glándulas y vasos sanguíneos.
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Amyloidosis, kidney, cross section, dog. Note the blue-black foci, which are glomeruli-containing amyloid stained by Lugol’s iodine (arrows)
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Amyloidosis, kidney, dog. The renal glomerulus contains large amounts of pale homogeneous eosinophilic material, which is amyloid. H&E stain.
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Riñón Vaso sanguíneo
Bazo
Amiloidosis = amiloide = almidón
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Hepatic amyloidosis
This is usually associated with chronic immunoglobulin stimulation. Horse.
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Diabetes mellitus
Amyloidosis of Islets of Langerhans
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Crystalloids, kidney, dog. Note the elongated crystals in the nuclei of the hepatocytes
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Viral inclusion bodies, brain, dog. Note the intranuclear eosinophilic inclusion bodies in glial cells. H&E stain.
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Lead inclusion bodies, kidney, dog. The inclusions in the nuclei of these renal tubular epithelial cells are difficult to see with an H&E stain (arrows). Inset: An acid-fast stain is useful in identifying lead inclusions, which stain red. Ziehl Neelsen stain.
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WILLIAM KURELEK (1927-77)
The Maze (Canada, 1953)
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