Stress can be physical or mental.

Stress results when something causes your body to behave as if it were under attack. Sources of stress can be
physical, like injury or illness. Or they can be mental, like problems in your marriage, job, health, or finances.

When stress occurs, the body prepares to take action. This preparation is called the fight-or-flight response. In
the fight-or-flight response [1], levels of many hormones shoot up. Their net effect is to make a lot of stored
energy — glucose and fat — available to cells. These cells are then primed to help the body get away from
danger.

Stres dapat bersifat fisik atau mental. Stres terjadi ketika sesuatu menyebabkan
tubuh Anda berperilaku seolah-olah sedang diserang. Sumber stres dapat berupa
fisik, seperti cedera atau penyakit. Atau bias dari mental, seperti masalah dalam
pernikahan, pekerjaan, kesehatan, atau keuangan Anda. Ketika stres terjadi, tubuh
bersiap untuk mengambil tindakan. Persiapan ini disebut respons fight-or-flight.
Dalam respon fight-or-flight, kadar banyak hormon meningkat. Efeknya membuat
banyak energi yang tersimpan - glukosa dan lemak - tersedia untuk sel. Sel-sel ini
kemudian disiapkan untuk membantu tubuh menjauh dari bahaya.

Physical and psychological stresses can induce a wide range of immunological alterations in the
cell mediated and humoral immunity1,2. Although the basic neurochemistry of the stress response
is now well understood, much remains to be discovered about how the components of this
system interact with one an- other, in the brain, and throughout the body3. Both negative and
positive stressors can lead to stress. The intensity and duration of stress changes, depending on
the circumstances and emotional condition of the person suffering from it and examples of
stressors ranges from sensory input such as pain, to life experiences such as poverty. Besides
releasing typical stress metabolites, characteristic enzymes and hormones, primary factors of
psychological stress situations, possible reactions and recognizable symptomatic organic changes
also show multi-factorial appearances1. Exposure to psychological stressors can modulate the
primary anti- body response and increased permanent stress levels can lead to pathological organ
changes, psychological alterations as well as psychosomatic diseases

Stres fisik dan psikologis dapat menyebabkan berbagai perubahan imunologis dalam sel yang dimediasi
dan imunitas humoral. Meskipun neurokimia dasar dari respons stres sekarang dipahami dengan baik,
masih banyak yang harus ditemukan tentang bagaimana komponen-komponen sistem ini berinteraksi
dengan satu sama lain, di otak, dan di seluruh tubuh. Stresor negatif dan positif dapat menyebabkan stres.
Intensitas dan lamanya dari perubahan stres, tergantung pada keadaan dan kondisi emosional orang yang
menderita itu dan contoh-contoh stresor berkisar dari input sensorik seperti rasa sakit, hingga
pengalaman hidup seperti kemiskinan. Selain melepaskan metabolit stres yang khas, enzim dan hormon
yang khas, faktor utama stres psikologis, reaksi yang mungkin dan perubahan organik simtomatik yang
dapat dikenali juga menunjukkan gejala multi-faktorial. Paparan terhadap stresor psikologis dapat
memodulasi respons antibodi primer dan peningkatan tingkat stres permanen dapat menyebabkan
perubahan organ patologis, perubahan psikologis serta penyakit psikosomatik.

Stres adalah respon tubuh yang tidak spesifik terhadap setiap kebutuhan tubuh yang terganggu,
suatu fenomena universal yang terjadi dalam kehidupan sehari-hari dan tidak dapat di hindari,
setiap orang mengalaminya. stres dapat berdampak secara total pada individu yaitu terhadap
fisik, psikologis, intelektual, sosial, dan spiritual, stres dapat mengancam keseimbangan
fisiologis.
Stres1 merupakan masalah umum yang terjadi dalam kehidupan umat manusia. Kupriyanov
dan Zhdanov (2014) menyatakan bahwa stres yang ada saat ini adalah sebuah atribut
kehidupan modren. Hal ini dikarenakan stres sudah menjadi bagian hidup yang tidak bisa
terelakkan. Baik di lingkungan sekolah, kerja, keluarga, atau dimanapun, stres bisa dialami
oleh sese- orang. Stres juga bisa menimpa siapapun termasuk anak-anak, remaja, dewasa,
atau yang sudah lanjut usia. Dengan kata lain, stres pasti terjadi pada siapapun dan
dimanapun. Yang menjadi masalah adalah apabila jumlah stres itu begitu banyak dialami
seseorang. Dampaknya adalah stres itu membahayakan kondisi fisik dan mentalnya.

Cannon merupakan peneliti pertama yang mengembangkan konsep stres yang dikenal
dengan “fight-or-flight response” pada tahun 1914 (Bartlett, 1998). Berdasarkan konsep yang
diperkenalkan Cannon tersebut, “the fight-or-flight response”, stres diartikan sebagai
respons tubuh terhadap sesuatu hal. Cannon menyatakan bahwa stres adalah sebagai
ganguan homeostasis yang menyebabkan perubahan pada keseimbangan fisiologis yang
dihasilkan dari adanya rangsangan terhadap fisik maupun psikologis.

The Canadian physiologist Hans Selye was the first scientist to study the effects of psychological stress on the human
body in 1936 [9]. He made a distinction between stress, stressor and stress reaction which he considered as a
complex phenomenon consisting of a set of nonspecific responses that result when the subject faces the situation. In
front of a danger, the system enters into a defense condition, trying to restore balance in di erent ways. It is an
adaptive mechanism, in which a series of physical changes predisposes the body to a “ flight or fight” reaction.
However, if the state of arousal continues over time, it can lead to negative consequences which Selye de nes “General
Adaptation Syndrome”.

Hans Selye, seorang fisiolog Kanada adalah ilmuwan pertama yang mempelajari efek dari
stress psikososial pada tubuh manusia di tahun 1936. Ia membuat perbedaan antara stress,
stressor dan reaksi stress yang ia anggap sebagai fenomena kompleks yang terdiri dari respon
nonspesifik ketika subyek menghadapi keadaan tersebut. Dalam menghadapi bahaya, sistem
tubuh akan berada dalam kondisi perlawanan, mencoba mengembalikan keseimbangan dalam
banyak cara. Ini adalah mekanisme adaptif, yang merupakan kumpulan perubahan fisik
terhadap respon flight-ot-fight. Akan tetapi, jika hal ini berlanjut, akan terjadi konsekuensi
negatif yang disebut Selye sebagai Sindroma Adaptasi Umum.

The author distinguishes three phases in response to a stressor. e rst is an “alarm reaction”: the homeostatic balance
is altered, generating a physiological mobilization comparable to a “natural biological doping”. Several functions
(blood glucose, blood pressure, muscle mobility, heartbeat, etc.) increase the availability of energy, making it easier to
face the situation.

Penulis membedakan tiga fase dalam respon terhadap suatu stressor. Yang pertama adalah
reaksi alarm: keseimbangan homeostatis terganggu, menghasilkan mobilisasi fisiologis yang
sebanding dengan doping biologis natural. Beberapa fungsi (glukosa darah, tekanan darah,
mobilitas otot, denyut jantung, dan lainnya) meningkatkan ketersediaan energi yang
membuatnya lebih mudah dalam menghadapi situasi. Ketika bahaya itu hilang, homeostasis
kan kembali dan badan kembali normal. Pada sebaliknya, jika stimulus stress tetap berlanjut,
ia akan memasuki fase kedua yang disebut resistensi atau adaptasi yang merupakan reaksi
biologis yang dimodifikasi. Selama bahaya itu ada, fungsi visceral dan parameter fisika-kimia
bertahan dalam kondisi yang terganggu. Ini menyiratkan pengeluaran energi yang cukup besar
dan tingkat fungsional sentral dan perifer yang lebih tinggi. Namun, individu tidak dapat
mengatasi lingkungan yang mengancam selamanya dan ketahanannya bervariasi sesuai dengan
faktor genetik, kognitif dan psikososial. Dalam jangka panjang, akan tejadi kelelahan dari
kemampuan adaptasi (fase ketiga), dan subyek akan merasakan sakit atau bahkan meninggal.
Hal ini terjadi ketika sumber bahaya tidak diatasi, tidak diinginkan dan berulang, sementara
jika stress hanya sebentar, badan akan kembali normal tanpa meninggalkan hal negatif

If the danger disappears, homeostasis is restored and the body returns to normal. On the

Prolonged exposure to adverse events, in fact, a ects hormonal balance, metabolism and immune function [13]. e
prolonged activation of the hypothalamus-pituitary-adrenal (HPA) axis, in particular, increases glucocorticoid levels,
causing pathologies related to hypercortisolism. Furthermore, this condition promotes the alteration of the immune
function and facilitates the development of central obesity, peripheral tissue resistance to insulin and glucose
intolerance.

In a physiological perspective, stress reaction is organized into two branches: the one governed by the sympathetic
nervous system, that operates quickly, and the one governed by neuroendocrine axis (HPA), that activates a delayed
response.

e rst one starts in the parvocellular nucleus of the hypothalamus, which is connected by a bundle of nerve bers to the
locus coeruleus, in the spinal cord. From here, the adrenal medulla is stimulated, so that it produces catecholamines
(adrenalin, noradrenalin, and dopamine), with physiological arousal

e functioning of the HPA axis, instead, begins from the paraventricular nucleus of hypothalamus, which releases
corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP). ese substances stimulate the pituitary gland
to produce adrenocorticotropic hormone (ACTH), that is released into the bloodstream and induces the adrenal
cortex to secrete cortisol [17,18].

e system is integrated because hypothalamic CRH and norepinephrine stimulate each other, according to a positive
feedback mechanism. However, there is also a negative feedback, which prevents the physiological activation from
lasting too long and damaging the body.

e hypothalamus, in fact, has particular receptors which detect cortisol levels and, depending on the case, activate the
axis more or deactivate it altogether.

Cortisol is one of the main actors mediating the e ect of stress on metabolism in general, and on glucose metabolism
in particular. Cortisol raises blood glucose levels by stimulating hepatic gluconeogenesis, and inhibiting the action of
insulin [36]. ese reactions - useful for initiating a ght or ight reaction - are not entirely suited to cope with the
stressors triggered by modern life, which are mostly relational, intangible and durable. e pressing rhythms imposed
by sedentary work, for example, do not involve an increase in energy requirements. e glucose mobilized from the
liver is not used and remains in the bloodstream, causing a rise in blood sugar. Moreover, the way by which
individuals evaluate events may in uence these reactions: an anxious person may anticipate di culties and amplify the
feeling of danger in the face of everyday situations. is anxiety may generate a state of perpetual alarm, that can induce
chronic hypercortisolism,
Kortisol adalah salah satu faktor utama yang memediasi efek stres pada
metabolisme secara umum, dan pada metabolisme glukosa pada khususnya.
Kortisol meningkatkan kadar glukosa darah dengan menstimulasi glukoneogenesis
hati, dan menghambat kerja insulin. Reaksi-reaksi ini berguna untuk memulai reaksi
ght atau ight - tidak sepenuhnya cocok untuk mengatasi stres yang dipicu oleh
kehidupan modern, yang sebagian besar relasional, tidak berwujud dan tahan lama.
Misalnya, ritme yang menekan yang dipaksakan oleh pekerjaan tidak bergerak, tidak
melibatkan peningkatan kebutuhan energi. Glukosa yang dimobilisasi dari hati tidak
digunakan dan tetap berada dalam aliran darah, menyebabkan peningkatan gula
darah. Selain itu, cara individu mengevaluasi peristiwa dapat memengaruhi reaksi-
reaksi ini: orang yang gelisah dapat mengantisipasi kesulitan dan memperkuat
perasaan bahaya dalam menghadapi situasi sehari-hari. Kecemasan dapat
menimbulkan keadaan alarm terus-menerus, yang dapat menyebabkan
hiperkortisolisme kronis

Stress is defined as the body response to any demand made on it. This response has two divisions that
are specific response and non-specific response. Specific response is the one which is actual response
to the particular stimulus that involves only a particular body system. However, non-specific response
is the one which is common to any type of stress and involves different body systems and leads to
fight or flight response. This is a favorable response, providing that the stress is physical stress which
is acute. This elevation of blood glucose is seen not only in physical stress but also other form of
stress such as psychosocial stress which is experienced in routine day lifestyle. Psychosocial stress
does not require increase in the blood glucose levels. Moreover, if the individual undergoes this type
of stress daily, there will be elevated blood glucose levels. However, chronic stress leads to several
deleterious effects. Stimulation of the secretion of different hormones during stress elevates blood
glucose levels.

Stres didefinisikan sebagai respons tubuh terhadap setiap permintaan yang dibuat padanya. Respons ini
memiliki dua bentuk yaitu respons spesifik dan respons non-spesifik. Respons spesifik adalah respons
aktual terhadap stimulus tertentu yang hanya melibatkan sistem tubuh tertentu. Namun, respons non-
spesifik adalah respons yang umum terjadi pada semua jenis stres dan melibatkan sistem tubuh yang
berbeda dan mengarah pada respon fight or flight. Ini adalah respons yang paling sering terjadi, di mana
stres adalah stres fisik yang akut.
Peningkatan glukosa darah ini tidak hanya terlihat pada stres fisik tetapi juga bentuk stres lainnya seperti
stres psikososial yang dialami dalam gaya hidup sehari-hari. Stres psikososial tidak memerlukan
peningkatan kadar glukosa darah. Akan tetapi, jika individu mengalami jenis stres yang sama setiap hari,
akan terjadi peningkatan kadar glukosa darah. Namun, stres kronis menyebabkan beberapa efek buruk.
Stimulasi sekresi berbagai hormon selama stres meningkatkan kadar glukosa darah.

Stress can be managed through the use of behavioral stress management programs or through the
administration of anxiolytic medications. Both types of interventions have been reported to improve
glycemic control

The experience of stress is associated with the release of counter- regulatory hormones and energy
mobilization, often resulting in elevated glucose levels (1,2). Several studies have demonstrated a
relationship of stress to glycemic control.

Jama punya di bawah

Generally, stressful events are thought to influence the patho- genesis of physical disease by causing
negative affective states (eg, feelings of anxiety and depression), which in turn ex- ert direct effects on
biological processes or behavioral pat- terns that influence disease risk.1 Exposures to chronic stress are
considered the most toxic because they are most likely to result in long-term or permanent changes in the
emo- tional, physiological, and behavioral responses that influ- ence susceptibility to and course of
disease.1,2 This in- cludes stressful events that persist over an extended duration (eg, caring for a spouse
with dementia) or brief focal events that continue to be experienced as overwhelming long af- ter they
have ended (eg, experiencing a sexual assault)
Behavioral changes occurring as adaptations or coping re- sponses to stressors such as increased
smoking, decreased ex- ercise and sleep, and poorer adherence to medical regimens provide an important
pathway through which stressors in- fluence disease risk. Stressor-elicited endocrine response pro- vides
another key pathway. Two endocrine response sys- tems are particularly reactive to psychological stress:
the hypothalamic-pituitary-adrenocortical axis (HPA) and the sympathetic-adrenal-medullary (SAM)
system. Cortisol, the primary effector of HPA activation in humans, regulates a broad range of
physiological processes, including anti- inflammatory responses; metabolism of carbohydrates, fats, and
proteins; and gluconeogenesis. Similarly, catechol- amines, which are released in response to SAM
activation, work in concert with the autonomic nervous system to exert regu- latory effects on the
cardiovascular, pulmonary, hepatic, skel- etal muscle, and immune systems. Prolonged or repeated ac-
tivation of the HPA and SAM systems can interfere with their control of other physiological systems,
resulting in in- creased risk for physical and psychiatric disorders.

That HPA and SAM systems mediate the effects of stress on disease is supported by experimental
evidence from ani- mal as well as human studies that show a wide variety of stressful stimuli provoke
activation of these systems. How- ever, stress also may influence disease risk through its ef- fects on other
systems. For example, psychological stress has been found to impair vagal tone,4 which also can in- crease
disease risk, particularly for CVD.

Effects of stress on the regulation of immune and inflam- matory processes have the potential to influence
depres- sion; infectious, autoimmune, and coronary artery disease; and at least some (eg, virally
mediated) cancers.5 Psycho- logical stress might alter immune function through direct innervation of
lymphatic tissue, through release of HPA and SAM hormones that bind to and alter the functions of im-
munologically active cells, or through stress-induced be- havioral changes such as increased smoking.

It is likely that DM-induced cognitive decline has a multifactorial etiology through mul- tiple mechanisms
including blood glucose and direct effect of chronic hyperglycemia on the brain [4], blood lipid [5], blood
pressure [6], insulin resistance [7], hypoglycemia [8], chron- ic complication as micro and macro-vascular
complications (diabetic vasculopathy) [9], dysregulation of limbic-hypotha- lamic-pituitary-adrenal axis
(LHPA) (stress response) [10, 11], advanced glycation end products, in ammatory cytokines, oxidative
stress [12] and diabetes-related depression [13, 14]. It has been suggested that insulin antagonistic action
of hor- mones and neuropeptides like catecholamines (adrenaline, noradrenaline and dopamine), GCs,
sex steroids and adipo- kines as well as dysregulation of autonomic nervous activity may contribute to
the early development of insulin resistance (pre-diabetic condition) and T2DM [15]. Some of these factors
can directly impair glucose uptake capacity and this might be due to alterations in key proteins involved
in insulin’s in- tracellular signaling pathways [16]. Glucocorticoids (GCs) and glucose regulation are
closely linked. In T2DM, several recent studies point to the dysregulation of the LHPA with distur- bances
in glucose regulation leading to hypercortisolemia [10, 11]. Under physiological conditions, corticotropin-
releasing hormone (CRH) from the hypothalamus leads to adrencorti- cotropic hormone (ACTH) release
from the pituitary. This in turn stimulates secretion of GCs from the adrenal cortex. By acting on a wide
array of target tissues, GCs are important for successful adaptation (stress response). Once elevated, GCs
exert a negative feedback via the pituitary, hypothalamus and hippocampus [17]. GCs modulate a broad
range of neural functions, including stress reactivity and emotional respons- es; neuronal excitability and
plasticity, learning and memory, neurogenesis and neuronal death. Normal brain function re- quires
optimal levels of the GCs signaling and that deviation from this optimal level in either direction is highly
deleterious [18, 19]. Although acute cortisol elevations during stress are protective, chronically elevated
levels have mostly negative effects [17]. Disturbance in glucose regulation as insulin resis- tance and
T2DM are associated with hypercortisolemia [10- 20]. Chronic hyperglycemia and hypercortisolemia are
known to have deleterious effects on the hippocampus [17], an area of the brain responsible for learning
and memory (particularly episodic and declarative memory and especially important for accurate and
reliable contextual memory) [21] and also with the highest colocalization of in insulin [22], glucocorti-
coid [21-23] and glutamate [24] receptors. However, reports on the relationship between
hypercortisolemia and cognitive impairment in patients with hyperglycemia are few or even inconsistent
and controversial.
In a physiological perspective, stress reaction is organized into two branches: the one governed by the sympathetic
nervous system, that operates quickly, and the one governed by neuroendocrine axis (HPA), that activates a delayed
response.

Dalam perspektif fisiologis, reaksi stres diatur ke dalam dua cabang: yang diatur oleh
sistem saraf simpatik, yang beroperasi dengan cepat, dan yang diatur oleh sumbu
neuroendokrin (HPA), yang mengaktifkan respons tertunda.

The first one starts in the parvocellular nucleus of the hypothalamus, which is connected by a bundle of nerve fibers
to the locus coeruleus, in the spinal cord. From here, the adrenal medulla is stimulated, so that it produces
catecholamines (adrenalin, noradrenalin, and dopamine), with physiological arousal

Yang pertama dimulai pada nukleus parvocellular dari hipotalamus, yang

dihubungkan oleh ikatan serabut saraf ke locus coeruleus, di medula spinalis. Dari
sini, medula adrenal dirangsang, sehingga menghasilkan katekolamin (adrenalin,
noradrenalin, dan dopamin) secara fisiologis.

The functioning of the HPA axis, instead, begins from the paraventricular nucleus of hypothalamus, which releases
corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP). ese substances stimulate the pituitary gland
to produce adrenocorticotropic hormone (ACTH), that is released into the bloodstream and induces the adrenal
cortex to secrete cortisol

Fungsi sumbu HPA, sebaliknya, dimulai dari inti paraventrikular hipotalamus, yang
melepaskan hormon pelepas kortikotropin (CRH) dan arginin vasopresin (AVP). Zat
ini merangsang kelenjar hipofisis untuk menghasilkan hormon adrenokortikotropik
(ACTH), yang dilepaskan ke dalam aliran darah dan menginduksi korteks adrenal
untuk mengeluarkan kortisol

The system is integrated because hypothalamic CRH and norepinephrine stimulate each other, according to a positive
feedback mechanism. However, there is also a negative feedback, which prevents the physiological activation from
lasting too long and damaging the body.

The hypothalamus, in fact, has particular receptors which detect cortisol levels and, depending on the case, activate
the axis more or deactivate it altogether.

Sistem ini terintegrasi karena CRH hipotalamus dan norepinefrin saling

menstimulasi, sesuai dengan mekanisme umpan balik positif. Namun, ada juga
umpan balik negatif, yang mencegah aktivasi fisiologis dari berlangsung terlalu lama
dan merusak tubuh. Hipotalamus, pada kenyataannya, memiliki reseptor khusus
yang mendeteksi kadar kortisol dan, tergantung pada kasusnya, mengaktifkan
sumbu lebih banyak atau menonaktifkannya sama sekali.