Rabu, 25 Januari 2012

CHOLESTEROL 5 - Atherosclerosis 1 - Arteriosclerotic vascular disease - ASVD - 动脉硬化 - 動脈硬化 - Dòngmài yìnghuà


Daftar Jamu Godog Kendhil Kencana >>>Jamu Godog Penurun Cholesterol – LEMAK NORMAL

Vývoj aterosklerotických změn
Stages of endothelial dysfunction in atheroscerosis

Aterosklerosis (Atherosclerosis - Arteriosclerotic vascular disease - ASVD - 动脉硬化 - 動脈硬化 - Dòngmài yìnghuà) adalah radang pada pembuluh darah manusia yang disebabkan penumpukan plak ateromatus (atheromatous plaque)1.
1 In pathology, an atheroma (from ἀθήρωμα (athērōma)=“tumor full gruel-like matter”) is an accumulation and swelling in artery walls that is made up of (mostly) macrophage cells, or debris, that contain lipids (cholesterol and fatty acids), calcium and a variable amount of fibrous connective tissue. Atheroma occurs in atherosclerosis, which is one of the three subtypes of arteriosclerosis; atherosclerosis, Monckeberg's arteriosclerosis and arteriolosclerosis.
Pemahaman hingga saat ini mengenai aterogenesis2, lintasan pembentukan aterosklerosis, adalah sebuah proses peradangan yang terjadi pada dinding pembuluh darah, yang terjadi dengan beberapa fase dan tahap. Pada fase awal, yang terjadi adalah disfungsi endotelial3 dengan degradasi ikatan dan struktur mosaik, sehingga memungkinkan senyawa yang terdapat di dalam plasma darah seperti LDL untuk menerobos dan mengendap pada ruang sub-endotelial akibat peningkatan permeabilitas. Endapan tersebut dengan perlahan akan mengecilkan penampang pembuluh darah dalam rentang waktu dekade. 
2 Atherogenesis is the developmental process of atheromatous plaques. It is characterized by a remodeling of arteries leading to subendothelial accumulation of fatty substances called plaques. The build up of an atheromatous plaque is a slow process, developed over a period of several years through a complex series of cellular events occurring within the arterial wall, and in response to a variety of local vascular circulating factors. One recent theory suggests that, for unknown reasons, leukocytes, such as monocytes or basophils, begin to attack the endothelium of the artery lumen in cardiac muscle. The ensuing inflammation leads to formation of atheromatous plaques in the arterial tunica intima, a region of the vessel wall located between the endothelium and the tunica media. The bulk of these lesions is made of excess fat, collagen, and elastin. At first, as the plaques grow, only wall thickening occurs without any narrowing. Stenosis is a late event, which may never occur and is often the result of repeated plaque rupture and healing responses, not just the atherosclerotic process by itself.
3 Endothelial dysfunction is a systemic pathological state of the endothelium (the inner lining of blood vessels) and can be broadly defined as an imbalance between vasodilating and vasoconstricting substances produced by (or acting on) the endothelium. Normal functions of endothelial cells include mediation of coagulation, platelet adhesion, immune function and control of volume and electrolyte content of the intravascular and extravascular spaces. Endothelial dysfunction can result from and/or contribute to several disease processes, as occurs in septic shock, hypertension, hypercholesterolaemia, diabetes, it can also result from environmental factors, such as from smoking tobacco products and exposure to air pollution.
Keberadaan makrofaga4 pada arterial intima5 ditelisik memiliki peran yang sangat vital bagi perkembangan aterosklerosis, dengan sekresi beragam sitokina yang mempercepat patogenesis ini. Hasil studi menunjukkan bahwa guratan aterosklerosis adalah senyawa fatty streak6 yang terdiri dari sel foam, sejenis makrofaga yang kaya akan lipid, yang disebut ateroma. Guratan ateroma akan berkembang menjadi plak fibrous7 yang terdiri dari lipid yang tertutup oleh sel otot halus dan kolagen. Proses penutupan mula-mula berjalan lambat, namun dengan penumpukan keping darah dan fibrin8, proses ini akan berkembang lebih cepat seiring dengan mekanisme fibrotik (fibrosis)9 yang bergantung trombosis10.
4 Makrofaga (bahasa Inggris: macrophage, MAC, bahasa Yunani: makros, "pemakan besar" dan bahasa Yunani: phagein, "makan") adalah sel pada jaringan yang berasal dari sel darah putih yang disebut monosit. Monosit dan makrofaga merupakan fagosit, berfungsi baik pada pertahanan tidak spesifik dan juga pada pertahanan spesifik vertebrata. Peran mereka adalah untuk memfagositosis selular dan patogen baik sebagai sel tak berubah atau bergerak, dan untuk menstimulasikan limfosit dan sel imun lainnya untuk merespon patogen.
Tunica intima
5 The tunica intima (or just intima) is the innermost layer of an artery or vein. It is made up of one layer of endothelial cells and is supported by an internal elastic lamina. The endothelial cells are in direct contact with the blood flow.
The inner coat (tunica intima) can be separated from the middle (tunica media) by a little maceration, or it may be stripped off in small pieces; but, on account of its friability, it cannot be separated as a complete membrane. It is a fine, transparent, colorless structure which is highly elastic, and, after death, is commonly corrugated into longitudinal wrinkles.
6 Fatty streak, though composed of macrophage white blood cells, not fat, is the term generally given to the earliest stages of atheroma, as viewed at autopsy, looking at the inner surface of arteries, without magnification.
The fatty streak is the first grossly visible lesion in the development of atherosclerosis. It appears as an irregular off white to yellow-white discoloration near the luminal surface of the artery. The streaks are not actually fat but small collections of monocyte-derived macrophages located beneath the inner, endothelial layer of arteries. The fatty streak mainly consists of foamy appearing macrophage cells, sometimes with some additional T lymphocytes, aggregated platelets, localized smooth muscle cells, etc. Fatty streaks may be precursor of atheromas and not all fatty streaks are destined to become fibrous plaques.
The macrophage cells, under a microscope, have a foamy-like appearance because of large collections of membrane bound vesicles within their cytoplasm. Since cholesterol within cells resides primarily within the cell membranes, the large accumulation of membranes results in an elevated local content of membrane bound cholesterol and other fats.
En-mass the foamy macrophages usually have an off white to yellow-white color and were named because they were thought to "look like" "streaks of fat" against the otherwise quite red/pink muscular tissue background forming the wall of arteries.
Almost all children above the age of 10 years show evidence of fatty streaks, with coronary fatty streaks beginning to form in the adolescent years.
7 The fibrous plaque is also localized under the intima, within the wall of the artery resulting in thickening and expansion of the wall and, sometimes, spotty localized narrowing of the lumen with some atrophy of the muscular layer. The fibrous plaque contains collagen fibers (eosinophilic), precipitates of calcium (hematoxylinophilic) and, rarely, lipid-laden cells.
8 Fibrin (also called Factor Ia) is a fibrous, non-globular protein involved in the clotting of blood. It is a fibrillar protein that is polymerised to form a "mesh" that forms a hemostatic plug or clot (in conjunction with platelets) over a wound site.
Fibrin is involved in signal transduction, blood coagulation, platelet activation, and protein polymerization.
9 Fibrosis adalah proses pembentukan jaringan fibrin. Fibrosis dapat terjadi setelah proses degenerasi leiomioma. Beberapa sitokina yang dapat menginduksi fibrosis antara lain, TGF-β, TNF-α, PDGF, CTGF, endotelin, GM-CSF, IL-1β, IL-6, IL-10, dan IL-13.
Beberapa jenis fibrosis yang dikenal antara lain, mediastinal, retroperitoneal, periorbital, retroorbital, paru, hati, sistik.
10 Thrombosis (Greek: θρόμβωσις) is the formation of a blood clot (thrombus; Greek: θρόμβος) inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets (thrombocytes) and fibrin to form a blood clot to prevent blood loss. Alternatively, even when a blood vessel is not injured, blood clots may form in the body if the proper conditions present themselves. If the clotting is too severe and the clot breaks free, the traveling clot is now known as an embolus.
Thromboembolism is the combination of thrombosis and its main complication, embolism.
When a thrombus occupies more than 75% of surface area of the lumen of an artery, blood flow to the tissue supplied is reduced enough to cause symptoms because of decreased oxygen (hypoxia) and accumulation of metabolic products like lactic acid. More than 90% obstruction can result in anoxia, the complete deprivation of oxygen, and infarction, a mode of cell death.
Dua kata lain yang mirip dan sering membingungkan adalah:
  • Arteriosklerosis11, menurunnya elastisitas pembuluh darah besar (arteri), akibat penebalan hialina12 pada pembuluh dengan diameter antara 40–150 μm yang menyebabkan stenosis13 konsentrik pada dinding pembuluh.
  • Arteriolosklerosis14, menurunnya elastisitas pembuluh darah kecil (arteriole)15
11 Arteriosclerosis refers to a stiffening of arteries.
Arteriosclerosis is a general term describing any hardening (and loss of elasticity) of medium or large arteries (from the Greek arterio, meaning artery, and sclerosis, meaning hardening)
It should not be confused with "arteriolosclerosis" or "atherosclerosis".
Also known by the name "myoconditis" which is outdated and no longer in general use.
12 The term hyaline (Greek: ὑάλινος ‘glassy’ from Greek: ὕαλος, ‘crystal, glass’) denotes a substance with a glass-like appearance.
In histopathological medical usage, a hyaline substance appears glassy and pink after being stained with haematoxylin and eosin — usually it is an acellular, proteinaceous material. An example is hyaline cartilage, a transparent, glossy articular joint cartilage.
Some mistakenly refer to all hyaline as hyaline cartilage, however hyaline is a descriptive term that applies to other material besides the cartilage itself.
Arterial hyaline is seen in aging, high blood pressure, diabetes mellitus and in association with some drugs (e.g. calcineurin inhibitors). It is bright pink with PAS staining.
13 A stenosis (plural: stenoses; from Ancient Greek στένωσις, "narrowing") is an abnormal narrowing in a blood vessel or other tubular organ or structure.
It is also sometimes called a stricture (as in urethral stricture).
The term coarctation is synonymous, but is commonly used only in the context of aortic coarctation.
14 Arteriolosclerosis is a form of cardiovascular disease affecting the small arteries and arterioles.
Types include hyaline arteriolosclerosis and hyperplastic arteriolosclerosis, both associated with vessel wall thickening and luminal narrowing that may cause downstream ischemic injury. Arteriolosclerosis is most often associated with hypertension and/or diabetes mellitus.
The following terms are similar, yet distinct, in both spelling and meaning, and can be easily confused: arteriosclerosis, arteriolosclerosis, and atherosclerosis. Arteriosclerosis is a general term describing any hardening (and loss of elasticity) of medium or large arteries (from the Greek arteria, meaning artery, and sclerosis, meaning hardening); arteriolosclerosis is any hardening (and loss of elasticity) of arterioles (small arteries); atherosclerosis is a hardening of an artery specifically due to an atheromatous plaque. The term atherogenic is used for substances or processes that cause atherosclerosis.
15 An arteriole ( /ɑrˈtɪəri.oʊl/) is a small diameter blood vessel in the microcirculation that extends and branches out from an artery and leads to capillaries.
Arterioles have muscular walls (usually only one to two layers of smooth muscle) and are the primary site of vascular resistance. The greatest change in blood pressure and velocity of blood flow occurs at the transition of arterioles to capillaries. This reduces the pressure and velocity of flow for gas and nutrient exchange to occur within the capillaries. Arterioles receive autonomic nervous system innervation and respond to various circulating hormones in order to regulate their diameter. Further local responses to stretch, carbon dioxide, pH, and oxygen also influence tone. Generally, norepinephrine and epinephrine (hormones produced by sympathetic nerves and the adrenal gland medulla)are vasoconstrictive acting on alpha 1-adrenergic receptors. However, the arterioles of skeletal muscle, cardiac muscle, and pulmonary arterioles vasodilates in response to these hormones acting on beta-adrenergic receptors. Generally, stretch and high oxygen tension increase tone,and carbon dioxide and low pH promote vasodilation. Pulmonary arterioles are a noteworthy exception as they vasodilate to high oxygen. Brain arterioles are particularly sensitive to pH with reduced pH promoting vasodilation. A number of hormones influce arteriole tone such as angiotensin II (vasoconstrictive),endothelin (vasoconstrictive),bradykinin (vasodilation), atrial natruretic peptide (vasodilation), and prostacyclin (vasodilation).
Blood pressure in the arteries supplying the body is a result of the work needed to pump the cardiac output (the flow of blood pumped by the heart) through the vascular resistance, usually termed total peripheral resistance by physicians and researchers. An increase in the media to lumenal diameter ratio has been observed in hypertensive arterioles (arteriolosclerosis)as the vascular wall thickens and/or lumenal diameter decreases.
Para penderita dengan sindrom resistansi insulin (insulin resistance syndrome)16 dan tahap awal diabetes tipe 2, menunjukkan pola arteriosklerosis11 yang ekstensif dan difusional, dengan peningkatan rasio peptida C.
16 Insulin resistance can be linked to diabetes, hypertension, dyslipidemia, cardiovascular disease and other abnormalities. These abnormalities constitute the insulin resistance syndrome. Because resistance usually develops long before these diseases appear, identifying and treating insulin-resistant patients has potentially great preventive value. Insulin resistance should be suspected in patients with a history of diabetes in first-degree relatives; patients with a personal history of gestational diabetes, polycystic ovary syndrome or impaired glucose tolerance; and obese patients, particularly those with abdominal obesity. Present treatment consists of sensible lifestyle changes, including weight loss to attain healthy body weight, 30 minutes of accumulated moderate-intensity physical activity per day and increased dietary fiber intake. Pharmacotherapy is not currently recommended for patients with isolated insulin resistance.
Obesity, type 2 diabetes mellitus (formerly known as non–insulin-dependent diabetes), hypertension, lipid disorders and heart disease are common in most Western societies and are collectively responsible for an enormous burden of suffering. Many people have more than one—and sometimes all—of these conditions, leading to the hypothesis that the coexistence of these diseases is not a coincidence, but that a common underlying abnormality allows them to develop. In 1988 it was suggested that the defect was related to insulin, and the insulin resistance syndrome was first described.1 It is estimated that this syndrome affects 70 to 80 million Americans.
16 Sindrom Resistensi Insulin Berisiko Diabetes
Sel-sel tubuh kita membutuhkan gula (glukosa) untuk energi. Agar glukosa dapat masuk ke dalam sel, tubuh akan mengeluarkan insulin, hormon yang berfungsi seperti kunci pembuka pintu sel, sehingga glukosa bisa masuk ke dalam sel. Pada sebagian orang, sel-selnya tidak merespon insulin dengan baik. Itulah sekilas gambaran yang terjadi pada resistensi insulin.
Menurut dr. Sandra Utami Widiastuti, Sp.PD dari Diabetic & Wound Care Clinic RS.Siloam Kebon Jeruk, Jakarta, resistensi insulin merupakan cikal bakal mengapa seseorang menderita diabetes tipe 2. "Insulinnya diproduksi oleh tubuh tapi tidak bisa bekerja dengan baik," katanya.
Obesitas (kegemukan) adalah salah satu penyebab resistensi insulin. Simpanan adiposa yang tinggi pada orang gemuk mengaktifkan paling tidak salah satu enzim, yaitu lipoprotein lipase yang meningkatkan konsentrasi asam lemak bebas dalam darah. Konsentrasi tinggi asam lemak bebas menstimulasi pelepasan sitokin seperti TNF-a (tumor necrosis factor-alpha) yang memicu resistensi insulin.
"Penurunan berat badan pada pasien diabetes, terutama yang obesitas salah satunya untuk mengurangi gejala resistensi insulin tadi," kata dokter Sandra. Selain obesitas, pola makan cepat saji yang tinggi kalori dan lemak juga beresiko meningkatkan resistensi insulin.
Pada awalnya, resistensi insulin memang belum menyebabkan diabetes klinis karena sel beta pankreas masih dapat mengompensasi sehingga terjadi hiperinsulinemi namun kadar glukosa darah sedikit meningkat. Pada sebagian orang gula darahnya masih normal. Kemudian jika sel beta mulai kelelahan, yang ditandai dengan peningkatan kadar glukosa, baru timbul diabetes melitus.
Peningkatan produksi insulin, sebagai respon terhadap resistensi insulin, memicu perubahan hormon-hormon reproduksi, terutama bertambahnya hormon testoteron pada wanita. Menurut Neal D.Barnard, MD dari Universitas Washington, resistensi insulin dapat menyebabkan penyakit kista indung telur pada wanita. Kondisi ini juga menyebabkan gangguan siklus ovulasi dan ketidaksuburan.
Resistensi insulin juga berkaitan risiko penyakit kardiovaskular. Dalam jangka panjang lonjakan kadar gula darah akan merusak pelbagai organ tubuh. Oleh karena itu mencegah resistensi insulin berarti juga mencegah komplikasi penyakit-penyakit lain.
17 C-peptide is a protein that is produced in the body along with insulin. First preproinsulin is secreted with an A-chain, C-peptide, a B-chain, and a signal sequence. The signal sequence is cut off, leaving proinsulin. Then the C-peptide is cut off, leaving the A-chain and B-chain to form insulin.
C-peptide should not be confused with c-reactive protein or Protein C.

Daftar Jamu Godog Kendhil Kencana >>>Jamu Godog Penurun Cholesterol – LEMAK NORMAL

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