接下來要看得是最後的部份,
要看細胞受傷後
細胞內的反應
細胞間的一些堆積
疾病引起的鈣
還有細胞的老化
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細胞內的變化
LYSOSOMAL CATABOLISM
lysosome會分解一些物質,透過下面兩種形式
Heterophagy : 分解由endocytosis吞入的一些東西
Autophagy: 分解細胞內部自己的東西.
雖然lysosome有許多酵素可以分解東西,但非萬能
有些東西無法分解,則會造成lysosome堆積,
有些藥物也會造成lysosome pH值上升,導致lysosome功能異常
INDUCTION (HYPERTROPHY) OF SMOOTH ENDOPLASMIC RETICULUM
sER是有一些分解毒物酵素所在地,所以細胞受到毒害,
這邊也是挺忙的
MITOCHONDRIAL ALTERATIONS
mit.在細胞受傷或是死亡中扮演重要角色
在壓力下 number, size, and shape of mitochondria都會改變
CYTOSKELETAL ABNORMALITIES
細胞骨架失常後,會影響細胞的運動,也在細胞內堆積一些骨架原料
除此之外, 像是Thin filaments受損,也會影響一些蛋白質的調節
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接下來談細胞間的一些堆積
Intracellular Accumulations
正常細胞會堆積一些water, lipids, proteins, and carbohydrates
而不正常的細胞會作些 abnormal synthesis or metabolism 所產生
的東西和pigment
Lipid堆積
許多種類的脂質都可以堆積, 例如CCl4等傷害肝臟後,造成
triglyceride 堆積
形態上, 在肝臟和心臟常出現 fatty change, 而造成在肝細胞(實質)
內出現泡狀油滴.這類可以用Red-O染色染出.
肝臟堆積lipid, 會大到3-6kg, 且呈現黃色(脂肪肝)
油滴堆積在心肌細胞, 則會出現small droplets.常由缺氧或是心肌炎導致
另外, 膽固醇堆積也常在 動脈硬化, 黃疸, 發炎等疾病中發現.
protein堆積
表徵是 unded, eosinophilic droplets, vacuoles, or aggregates
in the cytoplasm
有幾種情況可以看到這樣的現象
1.腎臟近曲小管發生滲漏protein. 導致protein堆積
2.細胞合成過量的分泌性蛋白質,例如為了製造免疫球蛋白
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.
在細胞外在HE染色下會出現玻璃狀. 當一些膠源蛋白所引起的fibrosis會出現
這樣的變化
GLYCOGEN
在醣類代謝異常時會出現glycogen的堆積.periodic acid schiff (PAS)的染色
可以染出
PIGMENTS
Exogenous Pigments
常見的就是一些空氣污染的碳和煤渣所引起.macrophage會去吞這些髒東西
Endogenous Pigments
1.
Lipofuscin is composed of polymers of lipids and phospholipids
complexed with protein. lipofusin 可能是由lipid過氧化,或是未飽和lipid的
membrane所衍生而來. 呈現棕色.
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: 鐵的一些沈積所造成.
hemoglobin-derived, golden yellow-to-brown, granular or
crystalline pigment in which form iron is stored in cells.
以下的一些狀況, 會造成鐵在組織器官的堆積, 稱為 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.
可以看切片圖,對於形態上的描述
Iron pigment appears as a coarse, golden, granular pigment lying
within the cell's cytoplasm
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Pathologic Calcification 鈣化
對於鈣化, 書上就先定義一下
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.
書中介紹兩種鈣化的原因
DYSTROPHIC CALCIFICATION 只存在於necrosis細胞附近的鈣化
形態上:
the calcium salts have a basophilic,
amorphous granular, sometimes clumped, appearance.
一但發生, 單一necrosis便會成回結晶的來源, 然後層層延伸.
形成psammoma bodies.
Pathogenesis成因:
兩個phase:
1) initiation (or nucleation)
胞內mit因為細胞死後,開始堆積鈣質
2) propagation
有下面幾步驟
(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 蔓延到正常組織的鈣化
當發生 hypercalcemia 時候會有這樣的鈣化情況發生.
造成hypercalcemia原因, 書上提了四點
(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.
這在身體的各組織中都可以見到.
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終於到了這章的末節 要談得是細胞老化
當細胞老化會有生理和結構上的改變, 並且減緩proliferation.
接下來分成幾個部份來談
Structural and Biochemical Changes with Cellular Aging.
老化細胞減弱了吸收營養的能力, 導致於削弱修復DNA功能.
而胞內也出現了許多變化
不正常的lobed nuclei, pleomorphic vacuolated mitochondria, decreased
endoplasmic reticulum, and distorted Golgi apparatus.
然後沈積一些色素
Replicative Senescence.
這個主要建立在 一個細胞具有有限的DNA複製能力, 然後提到telomer變短
然後慢慢造成cell cycle休止
Genes That Influence the Aging Process.
有些基因會跟老化有關係, 例如Foxo family
Accumulation of Metabolic and Genetic Damage.
最後談到當細胞/DNA累積許多傷害到一定的程度,會開始讓細胞出現老化現象.
第一章導讀大概就是這樣 ^^
※ 編輯: HIbaby 來自: 133.11.70.112 (06/12 15:25)