Pathophysiology of Dyspnea


Dyspnea is actually a common form of uncomfortable sensation in breathing. It is actually a common symptom which is found in several respiratory diseases. 1 Thus, it is commonly found in patients with cardiopulmonary disorders. However, it should be noted that dyspnea is not often a problem to be complained until the FEV1 has decreased below about 60% of the predicted value. 2

To understand more about the etiology or the cause of dyspnea, we should understand clearly about the pathophysiology of dyspnea itself. Hence, in this opportunity, we are going to discuss about pathophysiology of dyspnea.



Dyspnea is a subjective experience of breathing discomfort which is felt qualitatively in varying intensity. This sensation might derive from interactions of several aspects including physiological, psychological, social, and environmental factors. 3


Sense of Respiratory Effort

Respiratory sensations are actually the consequences of interactions between efferent – motor neuron, afferent – sensory neuron, and integrating neuron which processed the information in central nervous system; in respiratory cases, brain. These interactions influence the sense of respiratory effort. 3

Sense of respiratory effort is related with the ratio of pressure generated by respiratory muscles (Pbreath) to the maximum pressure generating capacity of the muscles (Pimax). 1

Hence, we can conclude that the sense of respiratory effort will increase when respiratory muscles exert higher pressure, such as when there is an increased in elasticity, resistive or threshold load. Similar thing happens when the pressure generating capacity of the muscles is decreased such as in weakened muscles due to fatigue or when the muscles experience mechanical disadvantage in increased lung volume. 1


Interactions between Sensory, Motoric, and Integrating Center

It has been mentioned previously that respiratory sensations are actually caused by the interactions of both motoric and sensory neurons with its integration center. All of these aspects can influence respiratory sensations variably. Interactions between these aspects will be explained by the figure below. 3 [Figure 1]

Figure 1. Algorithm for the inputs in dyspnea production 3



Motor efferent

When muscles are weak or fatigued, neural output from the motor cortex will increase via a corollary discharge. Thus, the neural signal will be sent to sensory cortex simultaneously with the transfer of motor output to ventilator muscles. 3

Sensory afferent

Sensory afferent functions to transfer information from chemoreceptors, mechanoreceptors, J-receptors, pulmonary vascular receptors, and metaboreceptors to be analyzed in central nervous system. 3

  • Chemoreceptors

Both peripheral and central chemoreceptors 1 such as chemoreceptors in carotid bodies and medulla will be activated in hypoxemia, acute hypercapnia, and acidemia condition. Activations of chemoreceptor will increase ventilation and may lead to a sensation in which the body is hungry of air. 1,3,4

  • Mechanoreceptors

These receptors are stimulated by bronchospasm and leads to chest tightness. Mechanoreceptors are spread throughout the respiratory system and are in charged for giving respond to mechanical stimuli. 1,3

  • Metaboreceptors

Metaboreceptors are richly found in skeletal muscles. When there are changes in local biochemical milieu of tissue active during exercise, it will be activated and lead to breathing discomfort. 3

  • Other sensory receptors

J-receptors are sensitive to interstitial edema. Meanwhile, when there are acute changes in pulmonary artery pressure, pulmonary vascular receptors will be activated and thus, lead to further air hunger. Hyperinflation might also lead to increase work of breathing, inability to get a deep breath, and unsatisfying breath. 3

Furthermore, Manning HL and Mahler DA said that there are classifications of receptors based on its location, which are upper airway receptors, chest wall receptors, and lung receptors. 1,4

  • Upper airway receptors

Based on the experiment, upper airway receptors will make the subject has a tendency to decrease their breathlessness intensity when sitting by a fan or open window. Thus, we can conclude that in normal subjects, the intensity of dyspnea or breathlessness can also be influenced by the receptors which are the distribution of trigeminal nerve. 4

  • Chest wall receptors

Chest wall is innervated by neuron receptors. Thus, joints, tendons, and muscles of the chest might influence ventilation and affect breathlessness sensations. For example, it has been found that such mechanical stimuli as vibration in the parasternal intercostal muscles will decrease dyspnea in both normal and COPD patients. 4

  • Lung receptors

Receptors in the lung will transmit signal gotten from the lung to central nervous system. These receptors include pulmonary stretch receptors – mechanoreceptors, chemoreceptors, irritant receptors, C-fibers (unmyelinated nerve endings) which is located in the alveolar wall and blood vessels – in charge of detecting interstitial congestion. Furthermore, vagal receptors are also reported to influence dyspnea depending on the activated receptors. For example, vagal irritant receptors will increase breathlessness and induce chest tightness or constriction. 1,4

Integration: efferent-reafferent mismatch

Intensity of dyspnea may increase when there is mistmatch between the feed-forward message to the ventilator muscles and feedback from receptors which monitor ventilator pump responses. This discrepancy is specifically related to mechanical derangement of ventilator pump, such as in asthma or chronic obstructive pulmonary disease (COPD). 3

Other factors influencing dyspnea

There are several factors such as emotional or affective factors which may contribute to dyspnea. For example, fear and acute anxiety might cause the worsening of dyspnea by resulting hyperinflation, increased breathing effort, and sense of unsatisfying breath. This is due to the alteration of sensory data interpretation or by leading breathing patterns which increase the physiologic abnormalities in the respiratory system. 3


Mechanism of Dyspnea in Common Respiratory Diseases

Dyspnea is a common symptom arisen in respiratory diseases. Each respiratory disease has different mechanism in inducing dyspnea. Details about mechanism of dyspnea in correlation with common respiratory diseases can be seen in the tabel below. 3 [Tabel 1]

Tabel 1. Mechanism of Dyspnea in Common Diseases 3




Dyspnea is a respiratory symptom which is characterized by discomfort or difficulty in breathing. 1,4 Dyspnea is common to be found in cardiorespiratory disorders, for example: dyspnea due to pneumonia arisen by Measles infection. Pneumonia caused by Measles infection can cause dyspnea by: 3

  • Increasing the work of breathing
  • Increasing drive to breathe
  • Stimulation of chemoreceptors due to hypoxemia and acute hypercapnia
  • Stimulation of pulmonary receptors





  1. Manning HL, Mahler DA. Pathophysiology of dyspnea. Monaldi Arch Chest Dis. 2001; 56(4):325-30.
  2. Grippi MA, Elias JA, Fishman JA, et al. Fishman’s pulmonary diseases and disorders. 5th New York: McGraw-Hill Education; 2015: 620.
  3. Longo DL, Fauci AS. Harrison’s gastroenterology and hepatology. NewYork: The McGraw-Hill; 2010:47e1-5.
  4. Epstein FH. Mechanism of Disease. N Engl J Med. 1995; 333(23):1547-53.

Diagnosis of Heart Failure


We know that when a patient comes to the doctor, patient will come with complaints; giving doctor symptoms like puzzles to be solved with a diagnosis. Sometimes, the symptoms include complaints from several systems in the body so that as physicians, we need to understand the correlation between each system to establish right diagnosis.

In this trigger, we learn about Congestive Heart Failure which is most likely to be caused by hypertension. However, it should be noted that there are several steps (algorithm) to help us in diagnosing patient so that we do not miss anything. Meanwhile, diagnosis of patient with suspected CHF includes history taking/anamnesis, physical examination, and such supporting diagnostic testing as electrocardiogram (ECG), thorax X-ray, echocardiogram, and laboratory test.



There are several clinical approaches need to be taken to be able to diagnose patient with heart failure. 1 Algorithm below shows the steps of diagnosing patient with suspected heart failure [Figure 1].


Figure 1. Algorithm for evaluation and diagnosis of heart failure.

King M, Kingery J, Casey B. Diagnosis and evaluation of heart failure. American Family Physician. 2012. 85(12): 1161-8.


History Taking

History taking / anamnesis (including alloanamnesis if the patient is unconscious) can be taken to points out possible etiologies and risk factors of heart failure in the patient. Most common etiologies and risk factors are the history or current illness of having coronary artery disease, hypertension, idiopathic cardiomyopathy, and valvular heart disease. History taking can also functions to know possible complication related to severity that the patient is having. 2,5


Physical Examination

Physical condition of the patient should be taken for identifying symptoms and characteristics of heart failure in the patient. Similar to other system’s physical examination, this examination includes inspection, palpation, auscultation, and percussion. 2

There are several criteria to diagnose heart failure. One of them which is widely used is Framingham criteria which is classified into 2 criteria, major and minor criteria. These criteria might be used to establish a diagnosis taken from symptoms gotten from physical examination session. These Framingham criteria includes: 1

  • Major criteria:
    • Acute pulmonary edema
    • Cardiomegaly
    • Hepatojugular reflex
    • Neck vein distension
    • Paroxysmal nocturnal dyspepsia or orthopnea
    • Rales
    • Third heart sound gallop
  • Minor criteria:
    • Ankle edema
    • Dyspnea on exertion
    • Hepatomegaly
    • Nocturnal cough
    • Pleural effusion
    • Tachycardia (>120 beats per minute)

Diagnosis of heart failure is taken when two major criteria or one major and two minor criteria of Framingham are met. 1


Electrocardiogram (ECG)

ECG is a tool to capture and observe electrical activity of the heart which is interpreted two-dimensionally (looking at the vector of heart movement). As we know, heart is a three-dimensional organ which moves three-dimensionally, too. 3 Thus, several leads are needed in each unique perspective to really interpret the movement of the heart two-dimensionally. There are twelve leads in ECG, which are then classified into several groups: 3

  • 3 standard limbs: 3
    • lead I: making the left arm the positive electrode and right arm negative electrode with angle of orientation 0 degree.
    • lead II: making legs the positive electrode and right arm negative electrode with angle of orientation 60 degrees.
    • lead III: making legs the positive electrode and left arm negative electrode with angle of orientation 120 degrees.
  • 3 augmented limbs: 3
    • lead aVL: making left arm positive and other limbs negative with angle of orientation -30 degrees
    • lead aVR: making right arm positive and other limbs negative with angle of orientation -150 degrees
    • lead aVF: making legs positive and other limbs negative with angle of orientation +90 degrees
  • 6 precordial leads: 3
    • V1: placed in the 4th intercostal space to the right of sternum
    • V2: placed in the 4th intercostal space to the left of sternum
    • V3: placed between V2 and V4
    • V4: placed in the 5th intercostal space in the midclavicular line
    • V5: placed between V4 and V6
    • V6: placed in the 5th intercostal space in the midaxillary line

Normally, heart pumps to anteriorly, slightly to the left, and downwards. Thus, these leads capture heart’s electrical activity in each’s own unique perspective. When the electrical activity of the heart moves towards the positive electrode of a lead, the lead will interpret a positive deflection in ECG result. On the other hand, when the electrical activity of the heart does not move towards the positive electrode of a lead (moves further apart), the lead will interpret a negative deflection in ECG result. For example, due to the fact that the electrical activity of the heart moves in different direction than lead aVF, ECG result in lead aVF will normally be negative deflection. 3,4


Figure 2. Waves, intervals, and segments in ECG

Sherwood L. Human physiology from cells to systems. 9th ed. Boston: Cengage Learning; 2016.


In ECG, there are P, QRS, T, and U waves which contribute to PR interval, PR segment, QRS interval, ST segment, QT interval. 3 Each of them represents different electrical activity of the heart. 3

  • P wave represents atrial depolarization.
  • PR interval represents the time from the start of atrial depolarization to the start of ventricular depolarization (normally lasts from 0.12-0.2 seconds).
  • PR segment represents time from the end of atrial depolarization to the beginning of ventricular depolarization.
  • QRS wave represents ventricular depolarization.
  • QRS interval represents duration of QRS complex, normally lasts from 0.06-0.1 seconds.
  • T represents ventricular repolarization.
  • ST segment represents the time from the end of ventricular depolarization to the start of ventricular repolarization, which is usually horizontal or slightly upsloping in all leads (isoelectric).
  • QT interval represents the time from the beginning of ventricular depolarization to the end of ventricular repolarization.
  • TP segment represents duration between the end of ventricular repolarization and the beginning of atrial depolarization. 4

Hypertrophy and Enlargement of the Heart

It should be taken into account that hypertrophy and enlargement is different. Hypertrophy accounts for an increase in muscle mass while enlargement means dilation of a particular chamber in the heart. 3


Figure 3. Hypertrophy and Enlargement of Left Ventricle

Thaler MS. The only EKG book you’ll ever need. 8th ed. New York: Wolters Kluwer; 2015.

Any changes in heart chamber (decreasing size due to increasing heart muscle mass and increasing size due to dilation) also affect ECG result by increasing time to depolarize, increasing amplitude since chamber generates more current and voltage, and eventually change the electrical axis of the heart. Normal mean electrical axis of the heart is usually between -30° to +90° while heart usually pumps between 0° to +90°, reflecting the electrical dominance of much larger left ventricle over the right ventricle. 3

As explained before, any changes of the heart can change mean electrical axis of the heart. Hypertrophy of the heart might change electrical axis of the heart accordingly to the hypertrophied side. For instance, if the mean electrical axis of the heart is shifted to -30° to -90°, the person is experiencing left axis deviation. On the other hand, right axis deviation is experienced when the mean electrical axis is shifted to +90° until +180°. 3


Figure 4. Axis of the Heart

Thaler MS. The only EKG book you’ll ever need. 8th ed. New York: Wolters Kluwer; 2015


Ventricular Hypertrophy

Ventricular hypertrophy may happen in both left ventricle and right ventricle. Each of them gives different ECG interpretation and different complication. Left ventricular hypertrophy might cause left-sided heart failure, systemic hypertension, and valvular disease. Meanwhile, right ventricular hypertrophy will also cause right-sided heart failure, congenital heart disease, and pulmonary disease. 3,5

Right ventricular hypertrophy induces right axis deviation, a swift of QRS complex axis to +90° and +180°. Other distinct characteristics of right ventricular hypertrophy is seen when: 3

  • Lead I have a negative deflection of QRS complex axis
  • R wave is larger than S wave in lead V1
  • S wave is larger than R wave in lead V6


Figure 5. Example of ECG Interpretation with Right Ventricular Hypertrophy

Thaler MS. The only EKG book you’ll ever need. 8th ed. New York: Wolters Kluwer; 2015.

On the other hand, the diagnosis of left ventricular hypertrophy is more complicated than right ventricular hypertrophy. In left ventricular hypertrophy, R wave amplitude should increase in leads overlying left ventricle while S wave amplitude should increase in leads overlying the right ventricle. There are several criteria needed to establish left ventricular hypertrophy diagnosis: 3

  • Precordial leads 3
    • R wave amplitude in lead V5 or V6 plus the S wave amplitude in lead V1 or V2 exceeds 3.5mV
    • R wave amplitude in lead V5 exceeds 2.6mV
    • R wave amplitude in lead V6 exceeds 2mV
    • R wave amplitude in lead V6 exceeds R wave amplitude in lead V5
  • Standard and augmented (limb) leads 3
    • R wave amplitude in lead aVL exceeds 1.1mV
    • R wave amplitude in lead aVF exceeds 2mV
    • R wave amplitude in lead I exceeds 1.3mV
    • R wave amplitude in lead I plus S wave amplitude in lead III exceeds 2.5mV


Figure 6. Example of ECG Interpretation with Left Ventricular Hypertrophy

Thaler MS. The only EKG book you’ll ever need. 8th ed. New York: Wolters Kluwer; 2015.


Atrial Enlargement

Both right and left ventricle hypertrophy can result in right and left atrium enlargement due to the pressure exceeds by hypertrophied ventricles might make atrioventricular valves insufficiency; inducing regurgitation to respective atria. Furthermore, atrial enlargement can also be caused by severe lung disease. 3,5

Right atrial enlargement will strengthen electrical activity of right atrium due to the fact that sinoatrial node (SA node) is located in the upper part of right atrial wall. Thus, there will be an increase P wave amplitude in lead II (we see lead II to observe P wave clearly due to the fact that lead II is located in the direction of normal electrical axis of the heart). Right atrial enlargement is commonly caused by severe lung disease – with electrocardiographic picture is commonly known as P pulmonale. 3


Figure 7. Example of ECG Interpretation with Right Atrial Enlargement

Thaler MS. The only EKG book you’ll ever need. 8th ed. New York: Wolters Kluwer; 2015.


On the other hand, due to fact that electrical activity of the heart travels from right atrium to left atrium, enlargement in left atrium might slower down electrical transmission. Thus, there will be an increase in duration of transmission, increase in amplitude of the second portion P wave, slowly drop to more than 0.1mV below the isoelectric line in lead V1. Left atrial enlargement is usually caused by mitral valve disease (the electrocardiographic picture is called P mitrale). 3


Figure 8. Example of ECG Interpretation with Left Atrial Enlargement

Thaler MS. The only EKG book you’ll ever need. 8th ed. New York: Wolters Kluwer; 2015.



In relation to the trigger, the man was experiencing difficulty in breathing, swollen feet (pitting edema), left margin of the heart shifted to anterior axillary line, jugular vein fully filled, increased heart sound 2, S3 gallop, wet rales in lung fields. According to the 5 major criteria and 3 minor criteria of Framingham; suggesting that the man was experiencing congestive heart failure. High possibility of this heart failure is caused by uncontrolled hypertension, causing left ventricular hypertrophy. This hypertrophied left ventricle of the heart is also supported by ECG result which shows:

  • Summation of R wave in lead V5 and S wave in V1 exceeds 3.5mV
  • R wave exceeds 2.6mV in lead V5
  • R wave exceeds 2mV in lead V6
  • R wave in lead I exceeds 1.3mV
  • Summation of R wave in lead I and S wave in lead III exceeds 2.5mV





  1. King M, Kingery J, Casey B. Diagnosis and evaluation of heart failure. American Family Physician. 2012. 85(12): 1161-8.
  2. Harrison TR, Resnick BF, Wintrobe MM, et al. Harrison’s principles of internal medicine. 19th New York: McGraw-Hill Education; 2015: 1500-5.
  3. Thaler MS. The only EKG book you’ll ever need. 8th ed. New York: Wolters Kluwer; 2015: 32-103.
  4. Sherwood L. Human physiology from cells to systems. 9th Boston: Cengage Learning; 2016: 312.
  5. Kumar V, Abbas AK, Aster JC. Robbins basic pathology. 9th ed. Philadelphia: Elsevier; 2013: 367-8.

Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is actually an immune-mediated chronic intestinal condition. It is more commonly found in women during adolescence or in young adults. 1 There are several factors which are predicted to be the causes of IBD, such as genetics, mucosal immune responses, epithelial defects, and combination of errant host interactions with intestinal microbiota. 1-2

Pathogenesis of Inflammatory Bowel Disease (IBD)


IBD is a hereditary disease that carries a 10% possibility of first-degree relative being affected. Children with IBD affected parents may have a 36% chance of being affected. Moreover, it is also stated that Ulcerative Colitis and Crohn’s Disease (major types of IBD) are associated with Turner’s syndrome, while Hermansky-Pudlak syndrome is associated with granulomatous colitis, another type of IBD. The table below explains the differences of tendencies leading to UC and CD. Furthermore, the occurrence of  CD is often correlated with NOD2 polymorphisms in which certain variants of NOD2 polymorphisms are not effective enough in combating luminal microbes which are why they are able to enter lamina propria and trigger inflammatory reactions. 1-2


Tabel 1. Epidemiology of IBD Harrison’s Gastroenterology and Hepatology. 2010.

Mucosal immune responses

Polarization of helper T cells to the TH1 type and TH17T cells are suggested be the factors contributing to the occurrence of the disease. Moreover, certain polymorphisms from IL-23 also gives protection from CD and UC while mucosal IL-13 production may increase in UC (lesser in CD), pointing that combination of mucosal immunity activation and immunoregulation suppression contribute to the development of UC and CD. 1

Epithelial defects

Certain NOD2 polymorphisms may be associated with the epithelial integrity, regarding the defects in intestinal epithelial tight junction barrier. However, it is also stated that CD patients with ATGI6LI mutations have abnormal Paneth cell granules which supposedly carry antimicrobial peptides. 1


As we know, the quantity of microbial organisms in the gastrointestinal lumen is large. The precise role of microbiota to IBD pathogenesis remains unclear despite of growing data of their effects to IBD pathogenesis. 1


Figure 1. Microscopic view of Ulcerative Colitis Robbins Basic Pathology 9th Ed. 2013.

When IBD is initiated, the immune inflammatory response is perpetuated by T-cell activation; activating such cytokines as IL-1, IL-6, and TNF to promote fibrogenesis, collagen production, activation of tissue metalloproteinases, and activation of blood coagulation factor in localized tissue. These activations of proinflammatory cells are not in balance with anti-inflammatory mediators, causing prolonged inflammation of the bowel. 1

There are 2 (two) major types of Inflammatory Bowel Disease (IBD), which are Ulcerative Colitis and Crohn’s Disease.

Ulcerative Colitis

Ulceratic Colitis (UC) is a mucosal disease which is often founded in rectum and extends towards proximal, involving all or part of the colon. It is an inflammatory reaction of the colon in which there is erythematous mucosa with a fine granular surface which looks like sandpaper in mild inflammation case. In severe inflammation, the mucosa is hemorrhagic, edematous, and ulcerated. In long-standing (chronic) disease, there might be inflammatory polyps (pseudopolyps) as a result of epithelial regeneration. The mucosa appears normal at first, however it proceeds to appear atrophic and featureless; thus, making the whole colon appears narrowed and shortened. 2


Figure 2. Macroscopic view of Ulcerative Colitis Robbins Basic Pathology 9th Ed. 2013.

Microscopically, we can see a distorted crypt architecture of the colon and the crypts may be bifid and reduced in number. Multiple basal lymphoid and basal plasma cells aggregates may also be seen. Additionally, neutrophils invasion can also be seen in the crypts, giving rise to cryptitis and crypt abscesses. 2


Figure 3. Microscopic view of Ulcerative Colitis Harrison’s Gastroenterology and Hepatology. 2010.

There are several sites of predilection in UC and we can classify them based on the locations. For example, pancolitis is UC which occurs at the entire colon. Disease limited to the rectum or rectosigmoid will be named as ulcerative proctitis or ulcerative proctosigmoiditis. Moreover, if it is located in the distal ileum, it will be called backwash ileitis. 1

Unlike in CD, there is no mural thickening, serosal surface appears normal and there is hardly any strictures occur. Nevertheless, the inflammation can damage muscularis propria and disturb neuromuscular function which may lead to toxic megacolon, carries high risk of perforation. Moreover, granulomas are also not present in UC. 1

UC has the symptoms of having diarrhea, rectal bleeding, tenesmus, passage of mucus, and crampy abdominal pain. Colonic motility is also altered by inflammation with rapid transit through the inflamed intestine. However, the diarrhea is mostly nocturnal. 2

Crohn’s Disease

Different with UC, Chron’s Disease (CD) can affect the whole gastrointestinal tract, starting from mouth to anus. However, the rectum area is commonly spared in CD condition (unlike CD). However, CD inflammatory lesions are segmental with skip areas in the midst of diseased intestine. 2

Small superficial ulcerations characterize mild disease while stellate ulcerations fuse longitudinally and transversely in the more active disease. However, pseudopolyps can also be found in CD similarly to UC. However, the CD lesions are transmural while UC lesions are only limited to mucosa and submucosa layers. Active CD is characterized by focal inflammation and formation of fistula tracts, which resolve by fibrosis and structuring of the bowel. Bowel wall thickens and becomes narrowed and fibrotic, proceeds to chronic recurrent bowel obstruction. 2 In severe case of transmural disease, mesenteric fat frequently extends around the serosal surface, this condition is commonly called as creeping fat. 1

Crypt abscess, groups of neutrophils infiltration in colonic crypt, will destruct the integrity of the colon These destructions will be followed by regeneration phase. This cycle will go on and lead to distortion of mucosal architecture, making the colonic crypts form bizarre branching shapes and unusual orientations to one another (which normally should be straight and parallel) 1


Figure 5. Macroscopic view of Crohn’s Disease. Robbins Basic Pathology 9th Ed. 2013.

As is explained before, aphthoid ulcerations and focal crypt abscesses with loose aggregations of macrophages form noncaseating granulomas in all of the bowel wall. Granulomas can be seen in lymph nodes, mesentery, peritoneum, liver, and pancreas. Furthermore, thickened mesentery projections which encase the colon, together with serosal and mesenteric inflammation will promote adhesions and fistula formation. 1-2


Figure 6. Microscopic view of Crohn’s Disease. Robbins Basic Pathology 9th Ed. 2013.

Moreover, there is also tendency of CD to lead to epithelial metaplasia which often takes the form of gastric antral-appearing glands (pseudopyloric metaplasia). Moreover, Paneth cell metaplasia may also occur in the left colon. Not to mention the noncaseating franylomas, which may rise in any area of intestinal wall (in both involved/diseased or uninvolved regions). 1

Patients with CD often have intermittent attacks of mild bloody diarrhea, fever, abdominal pain in lower right quadrant. This disease can be reactivated (thus resulting in recurrent symptoms) due to such external stimulations as physical or emotional stress, cigarette smoking, and specific dietary items. 1


Tabel 2. Differentiating CD and UC. Robbins Basic Pathology 9th Ed. 2013.

Indeterminate Colitis

UC and CD have similar symptoms and clinical manifestations to other diseases. For differentiating UC and CD themselves, they are often hard to be distinguished in up to 15% cases. This condition is called indeterminate colitis. 2 Patients with overlapping clinical symptoms of certain patients might still be treated effectively. However, it is recommended to differentiate UC and CD while we can as the evolving medical therapies and surgical management are specific to each type of IBD. 1 We can differentiate CD and UC by several aspects which have already been shown in the previous table and the table below:


Tabel 3. CD and UC differences based on clinical, endoscopic, and radiographic features. Harrison’s Gastroenterology and Hepatology. 2010.


  1. Kumar V, Abbas AK, Aster JC. Robbins Basic Pathology 9th Philadelphia: Elsevier; 2013: 587-91.
  2. Longo DL, Fauci AS. Harrison’s Gastroenterology and Hepatology. NewYork: The McGraw-Hill; 2010: 174-83.


Pilihan Terapi Klinis untuk Penderita Artritis Reumatoid

Artritis Reumatoid (AR) merupakan penyakit reumatik yang disebabkan oleh sistem autoimun. Etiologi dari penyakit ini belum diketahui. Akan tetapi dapat ditinjau dari sinovitis erosif yang simetris dan melibatkan jaringan ekstraartikular.

Prevalensi reumatik di Indonesia masih cukup tinggi, yaitu 23,6%-31,3% dengan penyakit AR sekitar 0,4% populasi di urban dan rural. Pada hasil survey epidemiologi di Malang, penduduk berusia di atas 40 tahun memiliki prevalensi RA senilai 0,6% di daerah kabupaten. Sementara di poliklinik reumatologi RSUPN Cipto Mangunkusumo Jakarta pada periode Januari hingga Juni 2007, terdapat angka insidensi RA sebesar 15,1%. Akan tetapi, prevalensi RA akan lebih besar ditemukan di wanita. Perbandingan prevalensi AR pada wanita dan pria adalah 3:1 pada semua kelompok umum, dengan prevalensi tertinggi terdapat pada dekade keempat dan kelima.

Sejatinya, AR memiliki 2 terapi umum yang dikhususkan untuk mencegah progresivitas dari AR yaitu dengan Disease Modifying Anti Rheumatic Drugs (DMARD) dan penggunaan agen biologik dan mengurangi rasa sakit dan inflamasi pada sendi yang terdiri dari Obat Anti Inflamasi Non Steroid (OAINS) serta kortikosteroid dosis rendah.

DMARD adalah suatu pilihan pengobatan yang terdiri dari obat anti reumatik seperti metotreksat (MTX), sulfasalazine, leflunomide, klorokuin basa, dan siklosporin. Tata laksana pengobatan ini dipercaya dapat mengurangi kerusakan sendi, mempertahankan integritas sehingga nantinya dapat meningkatkan produktivitas sendi dari pasien AR. Dengan penjelasan di mana diperlukan 7,5-25 mg/minggu dosis metotreksat untuk menurunkan kemotaksis PMN serta memengaruhi sintesis DNA; 2×500 mg – 3×1000 mg sulfasalasin per hari untuk menghambat angiogenesis dan migrasi PMN; 20mg/hari leflumonide untuk menghambat pembelahan auto reaktif limfosit T; 6.5 mg/kg bb/ hari klorokuin basa untuk menghambat lisosom; dan pelepasan IL-1, dan 2.5-5mg/kg bb siklosporin untuk menghambat sintesis IL-1 dan IL-2.

Di samping itu, agen biologik juga dapat digunakan untuk mencegah progresivitas dari AR. Namun, mengingat mahalnya biaya dan efek samping (TB, hepatitis B) dari terapi ini, rekomendasi pengobatan ini lebih baik dilakukan oleh dokter konsultan rematologi maupun spesialis penyakit dalam dengan pelatihan khusus. Agen biologik yang dimaksud ini dapat berupa etanercept dengan dosis 25 mg sc 2x/minggu atau 50mg sc/minggu; rituximab sebesar 1000 mg iv pada hari ke-0 dan ke-15, serta 8 mg tocilizumab per kilogram iv setiap 4 minggu.

Terapi mengurangi progesivitas AR juga harus dilaksanakan bersamaan dengan terapi pengurang rasa sakit dengan kortikosteroid oral maupun OINS. Pemberian kortikosteroid oral harus dalam jangka waktu sesingkat mungkin dengan dosis serendah mungkin yang digunakan untuk mencapai efek klinis. Akan tetapi, perlu diketahui bahwa penggunaan kortikosteroid oral tidak bersamaan dengan pemberian OAINS. Kortikosteroid oral dapat diberikan dengan dosis rendah (setara prednisone <7,5 mg sehari) maupun dosis sedang (7,5 – 30 mg sehari). Penggunaan kortikosteroid sebagai obat pengurang rasa sakit tentunya dapat menimbulkan beberapa efek samping seperti hipertensi, hiperglikemi, osteroporosis, katarak, dan ateroskelosis. Sehingga, penggunaan pasien yang menjalani terapi kortikosteroid oral juga harus diperhatikan dalam aspek ini.

Selain itu, OAINS juga dapat diberikan untuk mengurangi rasa sakit pasien AR. Penggunaan OAINS dilakukan sama dengan kortikosteroid oral, yaitu pemberian dengan dosis serendah mungkin dalam waktu sesingkat mungkin. Akan tetapi, kombinasi dari dua atau lebih OAINS harus dihindari dalam maksud menambah efektivitas dari terapi. Hal ini dilakukan untuk mengurangi efek samping yang didapatkan karena kombinasi OAINS tidak dapat menambah efektivitas dari terapi tersebut.



  1. Naimggolan O. Prevalensi dan determinan penyakit rematik di Indonesia. Mai Kedokt Indon. Desember 2009; 59(12): 289-94.
  2. Perhimpunan Reumatologi Indonesia. Diagnosis dan pengelolaan artritis reumatoid 2014.

What Actually Happens in Ageing


Recently, people are prone to forgetfulness, especially the elderly people. Moreover, there are so many cases about such neurodegenerative diseases as dementia and Alzheimer’s disease. These diseases affect person’s various abilities, starting from cognitive ability, memory, to coordination. However, these kind of diseases usually occur when people age, meaning that most neurodegenerative diseases cases are found in elderly.

These cases make us wonder whether aging makes people prone to neurodegenerative diseases. This question may even lead to another. For instance, does aging itself a normal physiologic process? Is it normal that people forget things as they age? These questions will be easier to be answered if we understand the normal process of aging as we can see what goes wrong in aging process, which are also going to be discussed in this opportunity.



People will absolutely age as they grow older and this ageing process will definitely lead to death. Therefore, it should be taken into account that aging is a normal physiologic process, not a pathogenic process.

Ageing induces various changes throughout human body. In the brain, ageing may cause changes in the brain size, vasculature, and cognitive. These changes occur in both molecular to morphology level of human body. 1

Physical changes

For physical changes in size, human brain shrinks as they age. Studies found that the rate of the declining weight and volume of the brain is approximately 5% per decade after people reach 40, this number could increase when people reach 70. The shrinking of the brain is caused by the shrinking of both gray and white matter as myelin sheath also decreases even in the normal ageing.  Furthermore, the prefrontal cortex is the most affected area in the shrinking of the brain size. It is followed by striatum, temporal lobe, cerebellar vermis, cerebellar hemispheres, and hippocampus with occipital cortex being the area which is least affected. The picture below is the example of the brain MRI in normal ageing: 2

normal brain healthy 75 yo woman

Normal brain – healthy 75 years old woman Reference: UCSF Memory and Aging Center. Overview of Ageing. 2016

This figure in healthy elderly is absolutely different than the brain morphology in Alzheimer’s disease elderly as the healthy ageing brain shows the symmetrical view of the brain and no significant changes in the hippocampus area. 3 The figure below will show you the damages brain in neurodegenerative diseases, such as Alzheimer’s disease.

brain with AD

Comparison between the brains of normal and AD patient Reference:

Cognitive changes

This cognitive change in ageing is highly associated with the memory. As we know, memory is divided into four major sections, such as episodic memory, semantic memory, procedural memory, and working memory in which the episodic and semantic memory being the ones which are affected in ageing. 1

Episodic memory is the memory for recalling information which is related about where and when the information was picked up. On the other hand, semantic memory is the memory which stores the meaning of something. 1

Changes in neurotransmitter

Despite several changes which are already explained above, decreasing of such neurotransmitters as serotonin and dopamine also increase in ageing. These changes are highly associated with the regulation of brain synaptic plasticity and neurogenesis. Apart from that, such substance which is related to neurotransmitter level as monoamine oxidase, may also increase while people age and act as the liberate free radicals, thus disturbing the homeostatic function of the brain, resulting in several neuronal death. 1

Vascular changes

Not only human body which ages, but human’s vasculature will also age. This will be resulting in the increasing blood pressure . Therefore, people especially elderly are prone to the stroke and ischaemia. There are studies which found that white matter lesion and hyperintensities are highly related to the increasing of several vascular disturbances, such as cardiovascular risk, reduction in cerebral blood flow, and cerebral reactivity. 1



Ageing is the normal physiologic process. Ageing brain will have several changes including the physical changes (shrinking in size), changes in neurotransmitter, vascular changes, cognitive changes, etc. When brain ages, it is normal to have forgetfulness in semantic and episodic memory. 1 However, the pathologic condition comes when the elderly is having neurodegenerative diseases such as Alzheimer’s disease, which damages several parts of the brain.




  1. Peters R. Ageing and the brain. Postgrad Med J. 2006 Feb; 82(964): 84-88.
  2. UCSF Memory and Aging Center. Overview of Aging [Internet]. San Francisco: University of California San Francisco. 2016 [cited date May 6th 2016]. Available from:
  3. Whalley LJ. Brain ageing and dementia: what makes the difference? The British Journal of Psychiatry. Nov 2002; 181 (5):369-71.

Is Genetically Modified Food (GMO) Really Good for Health?

As the technology and knowledge about genetics and microbiology have improved, there are thoughts about improving the quality of life, including eliminating or inserting certain genes to enhance the benefits of organism including plants, animals, etc. However, first of all, we should know what exactly is the genetically modified organism or food.

Genetically modified organism (GMO) or genetically modified food is a kind of food which has foreign genes (from other organism: plants or animals) in its genetic codes. Genetically engineered food may make the food be more nutritious, tastier, decreased use of pesticides, etc. 1 However, the effect of modified plants or animals may be harmful because they has unexpected genetic changes. Moreover, they can also interbreed with natural organisms thus creating contamination which could lead to extinction. They can also cause toxicity or allergic reactions in many people because of the modifications. 2




  1. Wax E. Genetically engineered foods [Internet]. Bethesda: United States National Library of Medicine. 2014 [last updated May 3, 2016; cited date May 18, 2016]. Available from:
  2. Genetic Science Learning Center. Genetically Modified Foods [Internet]. Salt Lake City: University of Utah. 2016 [cited date May 18, 2016]. Available from:

How to Prevent Your Babies from Cronobacter sakazakii Infection



Cronobacter sp., which is formerly called as Enterobacter sakazakii is a gram – negative pathogens which can survive in extremely dry conditions. This bacteria can be obtained from food and environment. Even though cases regarding Cronobacter infections are rare, infection due to this bacteria is extremely dreadful especially for young infants which are susceptible for this bacteria in their early weeks of life as this bacteria can live in powdered infant formula, powdered milk, herbal teas, starches, etc. 1



Cronobacter sakazakii is a bacteria which survive in dry condition and can cause severe blood infections (sepsis), meningitis, necrotizing enterocolitis (NEC), etc. 1-2 As it can survive in dry condition, it can live in powdered infant formula as powdered milk is not sterile unlike the liquid milk. 1 Therefore, several steps to prevent Cronobacter spp. infection is needed to decrease the risk of infants getting this infection.

As is stated by Hunter et al. 2 , Cronobacter sakazakii is relatively resistant to osmotic, heat, and dry stresses. By other means, it can survive in quite an extreme condition and even regular routine sterilization methods cannot really eliminate it. Several ways of preventions should be conducted to cease this matter, such as: 1-2

  • Promoting breast feeding
  • Using gamma radiation to sterilize utensils
  • Using Cronobacter sakazakii – targeted bacteriophage therapy to reduce bacterial growth
  • Strict hand washing and contact isolation of both affected and susceptible infants
  • Avoid any possible contaminations for powdered infant formula.
  • Using hot water (above 70 degrees C) to make formula
  • Using formula within 2 hours of preparation



To sum up, special and additional care should be conducted to prevent the risk of infection for Cronobacter sakazii in infants. As Cronobacter sakazii lives in powdered infant milk, steps to prevent the colonization of this bacteria may start from the preparation of the milk itself, from the hygiene of the utensils, usage of the formula, until promoting breast feeding (avoid intake of formula milk) to reduce the risk of Cronobacter sakazii infection.



  1. Hunter CJ, Petrosyan M, Ford HR, Prasadarao NV. Enterobacter sakazakii: an emerging pathogen in infants and neonates. Surgical Infections (Larchmt). 2008 Oct; 9(5): 533 – 39.
  2. National Center for Emerging and Zoonotic Infectious Diseases. Learn about Cronobacter Infection [Internet]. Atlanta: United States Department of Health and Human Services. 2016 [last updated April 13, 2016; cited date May 18, 2016]. Available from:

Pasta Gigi untuk Mengobati Luka Bakar, Apakah itu Benar?

Penggunaan pasta gigi sebagai cara pertolongan pertama pada luka bakar kerap sekali dilakukan oleh banyak orang di Indonesia maupun di negara Asia lainnya. Paskanya, sensasi dingin dan menyegarkan yang diberikan pasta gigi pada luka bakar sering kali dipercaya sebagai sensasi “menyembuhkan” dari pasta gigi tersebut. Akan tetapi, benarkah pasta gigi dapat menyembuhkan luka bakar?

Untuk mengetahui jawabannya, perlu kita selidiki sendiri komposisi standar dari suatu pasta gigi. Banyak pasta gigi yang beredar di Indonesia mengandung mentol maupun senyawa kimia lain yang membuat adanya sensasi dingin seperti yang kita rasakan ketika sedang mengosok gigi. Sensasi ini  jugalah yang membuat luka yang kita oles dengan pasta gigi terasa dingin dan menyegarkan. Sehingga, dalam aspek sensasi dingin ini, pasta gigi tidak terbukti dapat menyembuhkan luka bakar.

Sementara itu, Dr Ankur Bhatnagar dari Department of Plastic Surgery and Burns di Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGI), India, menambahkan bahwa pemberian pasta gigi pada luka bakar dapat meningkatkan resiko infeksi dan iritasi berlanjut karena senyawa – senyawa kimia yang terdapat pada pasta gigi tersebut, contohnya seperti Kalsium.

Lalu, apa yang harus kita lakukan sebagai pertolongan pertama pada luka bakar?

  1. Taruh area yang mengalami luka bakar dengan air mengalir hingga sensasi terbakar berhenti
  2. Tutup luka bakar dengan kain / kasa yang bersih
  3. Bawa ke dokter (rumah sakit terdekat maupun puskesmas) untuk penanganan luka lebih lanjut

Jadi, sudah tahu bukan bahwa menggunakan pasta gigi untuk mengobati luka bakar itu tidak benar dan bahkan membahayakan? Oleh sebab itu, mari kita hentikan penggunaan home remedy yang tidak benar itu dan ajarkan pula orang – orang di sekitar kita dalam memberikan pertolongan pertama pada luka bakar! ~sky

Fast info:

  1. Jangan gunakan pasta gigi untuk mengobati luka bakar
  2. Gunakan air mengalir sebagai pertolongan pertama dalam menangani luka bakar, lalu balut luka dengan kasa bersih steril
  3. Minta pertolongan dari tim medik



The Times of India. Never apply toothpaste on burn area say doctors [Internet]. [Place unknown]: Times News Network; 2013 [cited date June 29, 2016]. Available from: