接下来要看得是最後的部份, 要看细胞受伤後 细胞内的反应 细胞间的一些堆积 疾病引起的钙 还有细胞的老化 ------------------------------------- 细胞内的变化 LYSOSOMAL CATABOLISM lysosome会分解一些物质,透过下面两种形式 Heterophagy : 分解由endocytosis吞入的一些东西 Autophagy: 分解细胞内部自己的东西. 虽然lysosome有许多酵素可以分解东西,但非万能 有些东西无法分解,则会造成lysosome堆积, 有些药物也会造成lysosome pH值上升,导致lysosome功能异常 INDUCTION (HYPERTROPHY) OF SMOOTH ENDOPLASMIC RETICULUM sER是有一些分解毒物酵素所在地,所以细胞受到毒害, 这边也是挺忙的 MITOCHONDRIAL ALTERATIONS mit.在细胞受伤或是死亡中扮演重要角色 在压力下 number, size, and shape of mitochondria都会改变 CYTOSKELETAL ABNORMALITIES 细胞骨架失常後,会影响细胞的运动,也在细胞内堆积一些骨架原料 除此之外, 像是Thin filaments受损,也会影响一些蛋白质的调节 ---------------- 接下来谈细胞间的一些堆积 Intracellular Accumulations 正常细胞会堆积一些water, lipids, proteins, and carbohydrates 而不正常的细胞会作些 abnormal synthesis or metabolism 所产生 的东西和pigment Lipid堆积 许多种类的脂质都可以堆积, 例如CCl4等伤害肝脏後,造成 triglyceride 堆积 形态上, 在肝脏和心脏常出现 fatty change, 而造成在肝细胞(实质) 内出现泡状油滴.这类可以用Red-O染色染出. 肝脏堆积lipid, 会大到3-6kg, 且呈现黄色(脂肪肝) 油滴堆积在心肌细胞, 则会出现small droplets.常由缺氧或是心肌炎导致 另外, 胆固醇堆积也常在 动脉硬化, 黄疸, 发炎等疾病中发现. protein堆积 表徵是 unded, eosinophilic droplets, vacuoles, or aggregates in the cytoplasm 有几种情况可以看到这样的现象 1.肾脏近曲小管发生渗漏protein. 导致protein堆积 2.细胞合成过量的分泌性蛋白质,例如为了制造免疫球蛋白 3.Defects in protein folding HYALINE CHANGE The term hyaline usually refers to an alteration within cells or in the extracellular space, which gives a homogeneous, glassy, pink appearance in routine histologic sections stained with hematoxylin and eosin. 在细胞外在HE染色下会出现玻璃状. 当一些胶源蛋白所引起的fibrosis会出现 这样的变化 GLYCOGEN 在醣类代谢异常时会出现glycogen的堆积.periodic acid schiff (PAS)的染色 可以染出 PIGMENTS Exogenous Pigments 常见的就是一些空气污染的碳和煤渣所引起.macrophage会去吞这些脏东西 Endogenous Pigments 1. Lipofuscin is composed of polymers of lipids and phospholipids complexed with protein. lipofusin 可能是由lipid过氧化,或是未饱和lipid的 membrane所衍生而来. 呈现棕色. 2.Melanin; 成因: non-hemoglobin-derived, brown-black pigment formed when the enzyme tyrosinase catalyzes the oxidation of tyrosine to dihydroxyphenylalanine in melanocytes 3.Hemosiderin; 成因: 铁的一些沈积所造成. hemoglobin-derived, golden yellow-to-brown, granular or crystalline pigment in which form iron is stored in cells. 以下的一些状况, 会造成铁在组织器官的堆积, 称为 hemosiderosis (1) increased absorption of dietary iron, (2) impaired use of iron, (3) hemolytic anemias, and (4) transfusions because the transfused red cells constitute an exogenous load of iron. 可以看切片图,对於形态上的描述 Iron pigment appears as a coarse, golden, granular pigment lying within the cell's cytoplasm ------------------ Pathologic Calcification 钙化 对於钙化, 书上就先定义一下 Pathologic calcification is the abnormal tissue deposition of calcium salts, together with smaller amounts of iron, magnesium, and other mineral salts. It is a common process occurring in a variety of pathologic conditions. 书中介绍两种钙化的原因 DYSTROPHIC CALCIFICATION 只存在於necrosis细胞附近的钙化 形态上: the calcium salts have a basophilic, amorphous granular, sometimes clumped, appearance. 一但发生, 单一necrosis便会成回结晶的来源, 然後层层延伸. 形成psammoma bodies. Pathogenesis成因: 两个phase: 1) initiation (or nucleation) 胞内mit因为细胞死後,开始堆积钙质 2) propagation 有下面几步骤 (1) calcium ion binds to the phospholipids present in the vesicle membrane, (2) phosphatases associated with the membrane generate phosphate groups, which bind to the calcium, (3) the cycle of calcium and phosphate binding is repeated, raising the local concentrations and producing a deposit near the membrane, and (4) a structural change occurs in the arrangement of calcium and phosphate groups, generating a microcrystal, which can then propagate and perforate the membrane. METASTATIC CALCIFICATION 蔓延到正常组织的钙化 当发生 hypercalcemia 时候会有这样的钙化情况发生. 造成hypercalcemia原因, 书上提了四点 (1) increased secretion of parathyroid hormone (PTH) with subsequent bone resorption, as in hyperparathyroidism due to parathyroid tumors, and ectopic secretion of PTH-related protein by malignant tumors (Chapter 7); (2) destruction of bone tissue, occurring with primary tumors of bone marrow (e.g., multiple myeloma, leukemia) or diffuse skeletal metastasis (e.g., breast cancer), accelerated bone turnover (e.g., Paget disease), or immobilization; (3) vitamin D-related disorders, including vitamin D intoxication, sarcoidosis (in which macrophages activate a vitamin D precursor), and idiopathic hypercalcemia of infancy (Williams syndrome), characterized by abnormal sensitivity to vitamin D; and (4) renal failure, which causes retention of phosphate, leading to secondary hyperparathyroidism. 这在身体的各组织中都可以见到. ---------------------------------- 终於到了这章的末节 要谈得是细胞老化 当细胞老化会有生理和结构上的改变, 并且减缓proliferation. 接下来分成几个部份来谈 Structural and Biochemical Changes with Cellular Aging. 老化细胞减弱了吸收营养的能力, 导致於削弱修复DNA功能. 而胞内也出现了许多变化 不正常的lobed nuclei, pleomorphic vacuolated mitochondria, decreased endoplasmic reticulum, and distorted Golgi apparatus. 然後沈积一些色素 Replicative Senescence. 这个主要建立在 一个细胞具有有限的DNA复制能力, 然後提到telomer变短 然後慢慢造成cell cycle休止 Genes That Influence the Aging Process. 有些基因会跟老化有关系, 例如Foxo family Accumulation of Metabolic and Genetic Damage. 最後谈到当细胞/DNA累积许多伤害到一定的程度,会开始让细胞出现老化现象. 第一章导读大概就是这样 ^^ ※ 编辑: HIbaby 来自: 133.11.70.112 (06/12 15:25)