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CLINICAL THERAPEUTICS
1.
COMMON COLD
INTRODUCTION:
The common cold (also known as nasopharyngitis, rhinopharyngitis, acute coryza, or a cold)
is a viral infectious disease of the upper respiratory system which affects primarily the nose.
Symptoms include a cough, sore throat, runny nose, and fever which usually resolve in seven to
ten days, with some symptoms lasting up to three weeks. Well over 200 viruses are implicated in
the cause of the common cold; the rhinoviruses are the most common. Upper respiratory tract
infections are loosely divided by the areas they affect, with the common cold primarily affecting
the nose, the throat (pharyngitis), and the sinuses (sinusitis). Symptoms are mostly due to the
body's immune response to the infection rather than to tissue destruction by the viruses
themselves. The primary method of prevention is by hand washing with some evidence to
support the effectiveness of wearing face masks.
No cure for the common cold exists, but the symptoms can be treated. It is the most frequent
infectious disease in humans with the average adult contracting two to three colds a year and the
average child contracting between six and twelve. These infections have been with humanity
since antiquity.
HISTORY:
The cause of the common cold has only been identified since the 1950s while the disease has
been with humanity since antiquity. Its symptoms and treatment are described in the Egyptian
Ebers papyrus, the oldest existing medical text, written before the 16th century BCE. The name
"common cold" came into use in the 16th century, due to the similarity between its symptoms
and those of exposure to cold weather. In the United Kingdom, the Common Cold Unit was set
up by the Medical Research Council in 1946 and it was here that the rhinovirus was discovered
in 1956. In the 1970s, the CCU demonstrated that treatment with interferon during the incubation
phase of rhinovirus infection protects somewhat against the disease, but no practical treatment
could be developed. The unit was closed in 1989, two years after it completed research of zinc
gluconate lozenges in the prophylaxis and treatment of rhinovirus colds, the only successful
treatment in the history of the unit.
EPIDEMIOLOGY:
The common cold is the most common human disease and all peoples globally are affected.
Adults typically have two to five infections annually and children may have six to ten colds a
year (and up to twelve colds a year for school children). Rates of symptomatic infections
increase in the elderly due to a worsening immune system.
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ETIOLOGY:
Coronaviruses are a group of viruses known for causing the
common cold. They have a halo, or crown-like (corona)
appearance when viewed under an electron microscope. The
common cold is a viral infection of the upper respiratory tract.
The most commonly implicated virus is a rhinovirus (30–80%), a
type of picornavirus with 99 known serotypes. Others include:
coronavirus (10–15%), influenza (5–15%), human parainfluenza
viruses, human respiratory syncytial virus, adenoviruses, enteroviruses, and metapneumovirus.
Frequently more than one virus is present. In total over 200 different viral types are associated
with colds.
Poor immune function is also a risk factor for disease. Insufficient sleep and malnutrition have
been associated with a greater risk of developing infection following rhinovirus exposure; this is
believed to be due to their effects on immune function.
TRANSMISSION:
The common cold virus is typically transmitted via airborne droplets (aerosols), direct contact
with infected nasal secretions, or fomites (contaminated objects). Which of these routes is of
primary importance has not been determined. The viruses may survive for prolonged periods in
the environment and can be picked up by people's hands and subsequently carried to their eyes or
nose where infection occurs. Transmission is common in daycare and at school due to the close
proximity of many children with little immunity and frequently poor hygiene. These infections
are then brought home to other members of the family. There is no evidence that recirculated air
during commercial flight is a method of transmission. However, people sitting in close proximity
appear at greater risk. Rhinovirus-caused colds are most infectious during the first three days of
symptoms; they are much less infectious afterwards.
PATHOPHYSIOLOGY
The common cold is a disease of the upper respiratory tract.
The symptoms of the common cold are believed to be
primarily related to the immune response to the virus. The
mechanism of this immune response is virus specific. For
example, the rhinovirus is typically acquired by direct contact;
it binds to human ICAM-1 receptors through unknown
mechanisms to trigger the release of inflammatory mediators.
These inflammatory mediators then produce the symptoms. It
does not generally cause damage to the nasal epithelium. The
respiratory syncytial virus (RSV) on the other hand is
contacted by both direct contact and air born droplets. It then
replicates in the nose and throat before frequently spreading to
the lower respiratory tract. RSV does cause epithelium damage.
Human parainfluenza virus typically results in inflammation of the nose, throat, and bronchi. In
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young children when it affects the trachea it may produce the symptoms of croup due to the
small size of their airway.
COMPLICATIONS:
Often, symptoms of the common cold are no more than irritating. But, sometimes the common
cold can lead to a more serious infection, such as sinusitis, bronchitis, or ear infection, and
require antibiotics or other medications to get well. These are;
1. Sinusitis: Sinusitis is a fairly common complication of a cold among adults and older
children, occurring in an estimated 0.5-2% of cases. Sinusitis is an infection of the small,
air-filled cavities inside the cheekbones and forehead. Symptoms of sinusitis include:
 Pain and tenderness around your nose, eyes and forehead
 A blocked and runny nose
In most cases, the symptoms of sinusitis will resolve without the need for treatment.
2. Otitis media: Otitis media is a middle ear infection and a common complication of colds
in children who are under five years old. It occurs in an estimated 20% of cases.
Symptoms of otitis media include:
 Severe earache.
 A high temperature (fever) of or above 38°C (100°F).
 Flu-like symptoms, such as vomiting and lethargy (a lack of energy).
 Some loss of hearing.
Approximately 80% of cases of otitis media will resolve themselves without treatment,
usually within three days. Additional treatment is usually only required if your child has
repeated episodes of otitis media.
3. Acute bronchitis (also called a chest cold): The common cold poses a risk for
bronchitis and pneumonia in nursing home patients, and in other people who may be
vulnerable to infection. Some experts believe that the rhinovirus may play a more
significant role than the flu in causing lower respiratory infections in the vulnerable
population.
4. Aggravation of Asthma: Rhinovirus infections can aggravate asthma in both children
and adults. In fact, rhinovirus has been reported to be the most common infectious
organism associated with asthma attacks. Colds may promote allergic inflammation of
the airways, and increase the intensity of their responsiveness for weeks.
SIGNS AND SYMPTOMS
The typical symptoms of a cold include cough, runny nose, nasal congestion and a sore throat,
sometimes accompanied by muscle ache, fatigue, headache, and loss of appetite. A sore throat is
present in about 40% of the cases and a cough in about 50%, while muscle ache occurs in about
half. In adults, a fever is generally not present but it is common in infants and young children.
The cough is usually mild compared to that accompanying influenza. While a cough and a fever
indicate a higher likelihood of influenza in adults, a great deal of similarity exists between these
two conditions. A number of the viruses that cause the common cold may also result in
asymptomatic infections. The color of the sputum or nasal secretion may vary from clear to
yellow to green and does not predict the class of agent causing the infection.
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A cold usually begins with fatigue, a feeling of being chilled, sneezing and a headache, followed
in a couple of days by a runny nose and cough. Symptoms typically peak two to three days after
infection onset, and usually resolve in seven to ten days but some can last for up to three weeks.
In children, the cough lasts for more than ten days in 35–40% of the cases and continues for
more than 25 days in 10%.
High fever, significantly swollen glands, severe sinus pain, and a cough that produces mucus
may be signs that you have a complication or more serious illness. If you have any of these signs,
you should contact your healthcare provider.
DIAGNOSIS
The distinction between different viral upper respiratory tract infections is loosely based on the
location of symptoms with the common cold affecting primarily the nose, pharyngitis the throat,
and bronchitis the lungs. There however can be significant overlap and multiple areas can be
affected. The common cold is frequently defined as nasal inflammation with varying amount of
throat inflammation. Self diagnosis is frequent. Isolation of the actual viral agent involved is
rarely performed, and it is generally not possible to identify the virus type through symptoms.
MANAGEMENT
There are currently no medications or herbal remedies which have been conclusively
demonstrated to shorten the duration of infection. Treatment thus comprises symptomatic relief.
Getting plenty of rest, drinking fluids to maintain hydration, and gargling with warm salt water,
are reasonable conservative measures. Much of the benefit from treatment is however attributed
to the placebo effect.
Symptomatic treatment: Treatments that help alleviate symptoms include simple analgesics
and antipyretics such as ibuprofen and acetaminophen/paracetamol. Evidence does not show
that cough medicines are any more effective than simple analgesics and they are not
recommended for use in children due to a lack of evidence supporting effectiveness and the
potential for harm. In 2009, Canada restricted the use of over-the-counter cough and cold
medication in children six years and under due to concerns regarding risks and unproven
benefits. The misuse of dextromethorphan (an over-the-counter cough medicine) has led to its
ban in a number of countries.
In adults the symptoms of a runny nose can be reduced by first generation antihistamines;
however, they are associated with adverse effects such as drowsiness. Other decongestants such
as pseudoephedrine are also effective in this population. Ipratropium nasal spray may reduce
the symptoms of a runny nose but there is little effect on stuffiness. Second-generation
antihistamines however do not appear to be effective.
Due to lack of studies, it is not known whether increased fluid intake improves symptoms or
shortens respiratory illness and a similar lack of data exists for the use of heated humidified air.
One study has found chest vapor rub to be effective at providing some symptomatic relief of
nocturnal cough, congestion, and sleep difficulty.
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Antibiotics and antivirals: Antibiotics have no effect against viral infections and thus have no
effect against the viruses that cause the common cold. Due to their side effects they cause overall
harm; however, they are still frequently prescribed. Some of the reasons that antibiotics are so
commonly prescribed include: people's expectations for them, physicians' desire to do
something, and the difficulty in excluding complications that may be amenable to antibiotics.
There are no effective antiviral drugs for the common cold even though some preliminary
research has shown benefit.
Alternative treatments: There are many alternative treatments used for the common cold. As of
2010 there is insufficient evidence to recommend for or against either honey or nasal irrigation.
Studies suggested that Zinc, if taken within 24 hours of the onset of symptoms, reduces the
duration and severity of the common cold in healthy people. Due to wide differences between the
studies, further research may be needed to determine how and when zinc may be effective.
Vitamin C's effect on the common cold while extensively researched is disappointing, except in
limited circumstances, specifically, individuals exercising vigorously in cold environments.
Evidence about the usefulness of echinacea is inconsistent. Different types of echinacea
supplements may vary in their effectiveness. It is unknown if garlic is effective.
PREVENTION
Physical measure to prevent the spread of cold viruses has been deemed the only potentially
effective measure for prevention. Zinc supplementation may be effective at decreasing the rate of
colds. Routine vitamin C supplementation does not reduce the risk or severity of the common
cold, though it may reduce its duration. No vaccine has been developed for the common cold,
which can be caused by many different viruses. But you can take some common-sense
precautions to slow the spread of cold viruses:
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Wash your hands. Clean your hands thoroughly and often, and teach your children the
importance of hand washing.
Scrub your stuff. Keep kitchen and bathroom countertops clean, especially when
someone in your family has a common cold. Wash children's toys periodically.
Use tissues. Always sneeze and cough into tissues. Discard used tissues right away, and
then wash your hands carefully. Teach children to sneeze or cough into the bend of their
elbow when they don't have a tissue. That way they cover their mouths without using
their hands.
Don't share. Don't share drinking glasses or utensils with other family members. Use
your own glass or disposable cups when you or someone else is sick. Label the cup or
glass with the name of the person with the cold.
Steer clear of colds. Avoid close, prolonged contact with anyone who has a cold.
Choose your child care center wisely. Look for a child care setting with good hygiene
practices and clear policies about keeping sick children at home.
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2. TONSILLITIS
INTRODUCTION:
The term tonsils most commonly means the palatine tonsils, which can be seen in the back of the
human throat. The lingual tonsils, palatine tonsils and the nasopharyngeal tonsil are
lymphoepithelial tissues located near the oropharynx and nasopharynx. These immunocompetent
tissues are the immune system's first line of defense against ingested or inhaled foreign
pathogens. However, the fundamental immunological roles of tonsils have yet to be understood.
Tonsillitis is inflammation of the tonsils most commonly caused by a viral or bacterial infection.
Symptoms of tonsillitis include sore throat and fever while no treatment has been found to
shorten the duration of viral tonsillitis. Bacterial causes such as streptococcal pharyngitis are
treatable with antibiotics. It usually takes one to three weeks to recover.
Top
TYPES OF TONSILLITIS:
 On the basis of severity there are 3 types of tonsillitis;
1. Acute
tonsillitis:
It may be caused by Bacterial or Viral infection. It has rapid onset and short duration.
2. Subacute
tonsillitis:
Infection of the tonsils lasting from 3 weeks to 3 months is termed as Subacute tonsillitis.
3. Chronic
tonsillitis:
Here the episodes of tonsillitis last for long periods of time when not treated. Most often
are caused by bacterial infections.
EPIDEMIOLOGY:
In UK general practice, recurrent sore throat has an annual incidence of 100 per 1000 population.
In the US, sore throat accounts for 2.1% of ambulatory visits. Acute tonsillitis is more common
in children between the ages of 5 and 15 years. The prevalence of bacterial tonsillitis,
specifically group A beta-haemolytic streptococci (GABHS), is 15% to 30% of children with
sore throat and 5% to 15% of adults with sore throat. Acute tonsillitis is most commonly seen in
winter and early spring in temperate climates, although it may occur at any time of the year.
ETIOLOGY:
Virus: The most common causes of tonsillitis are adenovirus, rhinovirus, influenza, coronavirus,
and respiratory syncytial virus. It can also be caused by Epstein-Barr virus, herpes simplex virus,
cytomegalovirus, or HIV.
Bacteria: The second most common causes are bacterial. The most common bacterial cause is
Group A β-hemolytic streptococcus (GABHS), which causes strep throat. Less common bacterial
causes include: Staphylococcus aureus ( including methicillin resistant Staphylococcus aureus or
MRSA), Streptococcus pneumoniae, Mycoplasma pneumoniae, Chlamydia pneumoniae,
pertussis, Fusobacterium, diphtheria, syphilis, and gonorrhea. Anaerobic bacteria have been
implicated in tonsillitis. These include pigmented Prevotella and Porphyromonas, Fusobacterium
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and Actinomyces spp. The possible role of anaerobes in the acute inflammatory process in the
tonsils is supported by several clinical and scientific observations: anaerobes have been isolated
from the cores of tonsils of children and adults with recurrent GABHS and non streptococcal
tonsillitis, and peritonsillar and retropharyngeal abscesses in many cases without any aerobic
bacteria, their recovery as pathogens in well-established anaerobic infections of the tonsils
(Vincent's angina), the increased recovery rate of encapsulated pigmented Prevotella and
Porphyromonas spp. in acutely inflamed tonsils, and the response to antibiotics in patients with
non streptococcal tonsillitis.
Others: Sometimes, tonsillitis is caused by an infection of spirochaeta and treponema, in this
case called Vincent's angina or Plaut-Vincent angina.
PATHOPHYSIOLOGY:
Diseased tonsils are associated with decreased antigen transport, decrease antibody production
above baseline levels and chronic bacterial infection. Local inflammatory pathways result in
oropharyngeal swelling, oedema, erythema, and pain. Rarely, the swelling may progress to the
soft palate and uvula (uvulitis), or inferiorly to the region of the supraglottis (supraglottitis).
COMPLICATIONS
Complications resulting from tonsillitis are uncommon. Some of the problems that occur are
outlined below. These are;
1. Middle ear infection: Middle ear infection (otitis media) is when the fluid in the middle
ear, between the eardrum and inner ear becomes infected by bacteria. In most cases, the
infection clears by itself.
2. Quinsy: A much less common complication of tonsillitis is called quinsy. An abscess
may develop lateral to the tonsil during an infection, typically several days after the onset
of tonsillitis. This is termed a peritonsillar abscess (or quinsy). This is a collection of pus
(an abscess) that develops between the back of one of the tonsils and the wall of the
throat. Quinsy is relatively rare. Only 1 in 1,000 children with tonsillitis will go on to
develop quinsy.Quinsy is usually treated using a combination of antibiotics and surgery
to drain the pus from the abscess.
3. Septicemia: Rarely, the infection may spread beyond the tonsil resulting in inflammation
and infection of the internal jugular vein giving rise to a spreading septicaemia infection
(Lemierre's syndrome).
4. Sleep apnoea: If your child has persistent or recurring tonsillitis (chronic tonsillitis) it
may cause breathing difficulties during sleep. This is known as obstructive sleep apnoea.
Your child will not usually wake up during sleep, but their deep sleep will be disturbed.
This can make them feel very tired during the day. Children affected by sleep apnoea will
often snore or gasp loudly as they sleep. If your child develops sleep apnoea due to
tonsillitis, it would usually be recommended that their tonsils are surgically removed
(tonsillectomy).
5. Acute Suppurative cervical lymphadenitis:
6. Acute gangrenous tonsillitis:
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7. Edema of the larynx:
8. Other complications: Other complications of tonsillitis are now very rare and usually
only occur if an underlying bacterial infection is left untreated. They include:
 Scarlet fever : A condition that causes a distinctive pink-red skin rash
 Rheumatic fever: This causes widespread inflammation throughout the body, leading to
symptoms such as joint pain, skin rashes and jerky body movements
 Glomerulonephritis: An infection (swelling) of the filters in the kidneys that can cause
vomiting and loss of appetite.
SIGNS AND SYMPTOMS
Common symptoms of tonsillitis include:
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red and/or swollen tonsils
white or yellow patches on the tonsils
tender, stiff, and/or swollen neck
swollen lymph nodes
sore throat
cough
headache
sore eyes
body aches
earache
fever
chills
nasal congestions
ulceration
In cases of acute tonsillitis, the surface of the tonsil may be bright red and with visible white
areas or streaks of pus. Tonsilloliths occur in up to 10% of the population frequently due to
episodes of tonsillitis.
DIAGNOSIS
The diagnosis of GABHS tonsillitis can be confirmed by culture. Samples are obtained by
swabbing both tonsillar surfaces and the posterior pharyngeal wall are plated on sheep blood agar
medium. The isolation rate can be increased by incubating the cultures under anaerobic
conditions and using selective media. A single throat culture has a sensitivity of 90%-95% for
the detection of GABHS. False-negative results are possible if the patient received antibiotics.
The identification of GABHS requires 24 to 48 hours. The use of bacitracin disc provides
presumptive identification. Attempts to identify beta hemolytic streptococci other than group A
may be important in adults. Commercial kits containing group-specific antisera are available.
Rapid methods for GABHS detection (10–60 minutes), are available. Older antigen tests detect
the surface Lancefield group A carbohydrate. Newer tests identify GABHS serotypes using
nucleic acid (DNA) probes or polymerase chain reaction. Rapid detection kits have a sensitivity
of 85 to 90. Bacterial culture should be performed in cases of a negative rapid streptococcal test.
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True infection with GABHS, rather than colonization, is defined as the presence of >10 colonies
of GABHS per blood agar plate. However, this method is difficult to implement because of the
overlap between carriers and infected patients. An increase in antistreptolysin O (ASO)
streptococcal antibody titer 3–6 weeks following the acute infection can provide retrospective
evidence of GABHS infection. ASO titers are considered definitive proof of GABHS infection.
When GAHBS is not isolated, the clinician should seek other potential pathogens. However,
many of these organisms are part of the normal flora residing in the pharynx, making
interpretation of the results difficult. A finding of a membrane in the throat should prompt a
search for corynebacteria. Culture should be obtained from beneath the membrane, and use of a
special moisture-reducing transport medium is necessary. A heterophile slide test or other rapid
test for infectious mononucleosis can provide a specific diagnosis.
TREATMENT
Treatments to reduce the discomfort from tonsillitis symptoms include:
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Pain relief, anti-inflammatory, fever reducing medications (acetaminophen/paracetamol and/or
ibuprofen)
Sore throat relief (warm salt water gargle, lozenges, and warm liquids).
Bacterial cause treatment: If the tonsillitis is caused by group A streptococus, then antibiotics
are useful with penicillin or amoxicillin being first line. Cephalosporins and macrolides are
considered good alternatives to penicillin in the acute setting. A macrolide such as erythromycin
is used for people allergic to penicillin. Individuals who fail penicillin therapy may respond to
treatment effective against beta-lactamase producing bacteria such as clindamycin or
amoxicillin-clavulanate. Aerobic and anaerobic beta lactamase producing bacteria that reside in
the tonsillar tissues can "shield" group A streptococcus from penicillins. Third line drugs are
flouroquinolones such as septran.
Virus cause treatment: When tonsillitis is caused by a virus, the length of illness depends on
which virus is involved. Usually, a complete recovery is made within one week; however,
symptoms may last for up to two weeks. Chronic cases may be treated with tonsillectomy
(surgical removal of tonsils) as a choice for treatment.
3.
PHARYNGITIS
INTRODUCTION:
Pharyngitis comes from the Greek word pharynx meaning
throat and the suffix -itis meaning inflammation. It is an
inflammation of the throat. In most cases it is quite painful, and
is the most common cause of a sore throat. Like many types of
inflammation, pharyngitis can be acute, characterized by a rapid
onset and typically a relatively short course or chronic.
Pharyngitis can result in very large tonsils which cause trouble
swallowing and breathing. Pharyngitis can be accompanied by a
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cough or fever, for example, if caused by a systemic infection. Most acute cases are caused by
viral infections (40–80%), with the remainder caused by bacterial infections, fungal infections,
or irritants such as pollutants or chemical substances. Treatment of viral causes are mainly
symptomatic while bacterial or fungal causes may be amenable to antibiotics and anti-fungal
respectively.
CLASSIFICATION OF PHARYNGITIS:
Pharyngitis is a type of inflammation, most commonly caused by an upper respiratory tract
infection. It may be classified as acute or chronic.
i.
ii.
Acute pharyngitis: An acute pharyngitis may be catarrhal, purulent or ulcerative,
depending on the virulence of the causative agent and the immune capacity of the affected
individual.
Chronic pharyngitis: It is the most common otolaringologic disease and may be catarrhal,
hypertrophic or atrophic.
If the inflammation includes tonsillitis, it is called pharyngotonsillitis. Another sub classification
is nasopharyngitis (the common cold).
EPIDEMIOLOGY
Acute pharyngitis is the most common cause of a sore throat and sore throat and cough is
diagnosed in more than 1.9 million people a year in the United States. In U.K general practice,
recurrent sore throat has an annual incidence of 100 per 1000 population. Acute tonsilitis is most
commonly seen in winter and early spring in temperate climates, although it may occur at any
time of the year.
ETIOLOGY:
The majority of cases are due to an infectious organism acquired from close contact with an
infected individual.
A. Infectious causes:
a) Viral cause: A throat infection which tested negative for
streptococcus, thus presumably of viral origin. The white
exudate on the tonsils which frequently also occurs with a viral
infection. These comprise about 40–80% of all infectious cases
and can be a feature of many different types of viral infections.
 Adenovirus: The most common of the viral causes. Typically
the degree of neck lymph node enlargement is modest and the
throat often does not appear red, although it is very painful.
 Orthomyxoviridae: Which cause influenza, present with rapid
onset high temperature, headache and generalised ache. A sore
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throat may be associated.
 Epstein- Barr virus: Infectious mononucleosis ("glandular fever") caused by the EpsteinBarr virus. This may cause significant lymph gland swelling and an exudative tonsillitis
with marked redness and swelling of the throat. The heterophile test can be used if this is
suspected.
 Common cold: rhinovirus, coronavirus, respiratory syncytial virus, parainfluenza virus
can cause infection of the throat, ear, and lungs causing standard cold-like symptoms and
often extreme pain.
b) Bacterial causes: A number of different bacteria can infect the human throat. The most
common is Group A streptococcus, others include Corynebacterium diphtheriae,
Neisseria gonorrhoeae, Chlamydophila pneumoniae, and Mycoplasma pneumoniae.
 Streptococcal pharyngitis: Streptococcal pharyngitis or strep throat is caused by group A
beta-hemolytic streptococcus (GAS). It is the most common bacterial cause of cases of
pharyngitis (15–30%). Common symptoms include fever, sore throat, and large lymph
nodes. It is a contagious infection, spread by close contact with an infected individual. A
definitive diagnosis is made based on the results of a throat culture. Antibiotics are useful
to both prevent complications and speed recovery.
 Fusobacterium necrophorum: Fusobacterium necrophorum are normal inhabitants of the
oropharyngeal flora. Occasionally however it can create a peritonsillar abscess. In 1 out
of 400 untreated cases Lemierre's syndrome occurs.
 Diphtheria: Diphtheria is a potentially life threatening upper respiratory infection caused
by Corynebacterium diphtheriae which has been largely eradicated in developed nations
since the introduction of childhood vaccination programs, but is still reported in the Third
World and increasingly in some areas in Eastern Europe. Antibiotics are effective in the
early stages, but recovery is generally slow.
 Others: Few other causes are rare, but possibly fatal and include parapharyngeal space
infections, peritonsillar abscess, submandibular space infection & epiglottitis.
c) Fungal causes: Some cases of pharyngitis are caused by fungal infection such as
Candida albicans causing oral thrush.
B. Non-infectious
Pharyngitis may also be caused by mechanical, chemical or thermal irritation, for example cold
air or acid reflux. Some medications may produce pharyngitis such as pramipexole and
antipsychotics.
PATHOPHYSIOLOGY:
Pharyngitis is an inflammation of the pharynx that can lead to a sore throat. Etiologic agents are
passed through person-to-person contact, most likely via droplets of nasal secretions or saliva.
Symptoms often manifest after an incubation period ranging from 1 to 5 days, and occur most
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commonly in the winter or early spring. Outbreaks of pharyngitis may occur in households or
classrooms, and, infrequently, may be linked to food or animal sources. The most common
bacterial cause of pharyngitis, GABHS, is also known as Streptococcus pyogenes and may exist
as single, paired, or chained gram-positive cocci. These bacteria possess protein M, a potent
virulence factor that inhibits bacterial phagocytosis, as well as a hyaluronic acid capsule that
enhances its ability to invade tissues. Multiple exotoxins and two hemolysins (Streptolysin S and
Streptolysin O) further enhance the virulence of GABHS.
Respiratory tract infection by invasive begun to nasopharyngitis, and then step down to produce
supraglottic infection cellulitis, accompanied by significant inflammation and epiglottis epiglottis
Valley, spoon-shaped epiglottis wall, arytenoid cartilage and throat room with the inflammation.
Caused by the cases of Haemophilus influenzae is often accompanied by bacteremia.
Inflammation of the epiglottis mechanically block the respiratory tract, the respiratory difficulty
increased, resulting in carbon dioxide retention and hypoxia. Inflammatory disorders also
occurred in the removal of secretions: these factors combined can be fatal within hours of
suffocation.
COMPLICATIONS:
Complications may include;
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In general, complications throat (especially common in cases of bacterial pharyngitis)
consist of sinusitis, otitis media, epiglottis (inflammation of the epiglottis), mastoiditis
and pneumonia.
Recurrence of infection is usually because of non-compliance with treatment, bacterial
resistance to antibiotics or a new exposure.
Suppurative complications of bacterial throat infection occur as a result of dissemination
from the mucosa of the pharynx, either marrow or lymphatic route or by direct extension
(most common case of strep) and consist of: periamigdalian abscess, abscess
retrofaringian or cervical lymphadenitis.
Nesupurative complications (incidence 3%) specific group A streptococcal infections in
rheumatic fever consists of (RAA) poststreptococica glomerulonephritis and toxic shock
syndrome.
Complications of infectious mononucleosis refers to: splenic rupture (justifying the
necessity of avoiding contact sports for 6 weeks), hepatitis, Guillain Barre syndrome,
encephalitis, hemolytic anemia, myocarditis, nasopharyngeal carcinoma. Use of penicillin
in cases of infectious mononucleosis has resulted in a 100% incidence of rash (rash).
SIGN AND SYMPTOMS:
The main symptom is a sore throat. Other symptoms may include:





Fever
Headache
Joint pain and muscle aches
Skin rashes
Swollen lymph nodes in the neck
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DIAGNOSTIC APPROACH:
It is hard to differentiate a viral and a bacterial cause of a sore throat based on symptoms alone.
Thus often a throat swab is done to rule out a bacterial cause.
During diagnosis of phyrangitis, following steps should be taken, these are;
1. Diagnosis may be aided by the Centor criteria. That is;
 Fever
 No Cough
 Tonsilar exudate
 Tender anterior cervical lymph nodes.
 Abdominal pain, nausea and vomiting also are common in children.
2. Conduct a physical examination: The most likely findings include a red, inflamed throat
and uvula. Other common sighs of pharyngitis include swollen tonsils with grayish-white
patches and swollen lymph nodes.
3. Take a throat culture by swabbing the tonsils and posterior pharynx vigorously, and
culture the sample for two days in sheep blood agar. The false negative rate for a properly
performed throat culture test is 5 to 10 percent.
4. Run rapid antigen detection tests. These tests are more expensive than throat cultures and
can be completed in minutes at the bedside. Rapid antigen detection tests that use
chemiluminescent DNA probes have sensitivities and specificities that are comparable to
throat cultures.
5. Elevated antibody levels will confirm a recent group A Streptococcus infection and also
may be helpful in diagnosing complications such as acute rheumatic fever. The most
common antibodies to test for are antideoxyribonuclease B and antistreptolysin O.
TREATMENT:
The majority of time treatment is symptomatic. Specific treatments are effective for bacterial,
fungal, and herpes simplex infections.
Medications:





Analgesics such as NSAIDs and acetaminophen can help reduce the pain associated with
a sore throat. (Note: Don't use salicylates, like aspirin, for influenza: Increased risk of
Reyes Syndrome)
Steroids (such as dexamethasone) have been found to be useful for severe pharyngitis.
Viscous lidocaine relieves pain by numbing the mucus membranes.
Antibiotics are useful if a bacterial infection is the cause of the sore throat. For viral
infections, antibiotics have no effect.
Oral analgesic solutions, the active ingredient usually being Phenol, but also less
commonly Benzocaine, Cetylpyridinium chloride and/or Menthol. Chloraseptic and
Cepacol are two examples of brands of these kinds of analgesics.
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Alternative medicines:
Alternative medicines are promoted and used for the treatment of sore throats. Using them to
treat viral infections helps strengthen bacteria and make them resistant to antibiotics. The
following tips may help your sore throat feel better:






Drink warm liquids such as lemon tea or tea with honey.
Gargle several times a day with warm salt water (1/2 tsp of salt in 1 cup water).
Drink cold liquids or suck on popsicles.
Suck on hard candies or throat lozenges. Young children should not be given such
products because they can choke on them.
A cool-mist vaporizer or humidifier can moisten and soothe a dry and painful throat.
Try over-the-counter pain medications, such as acetaminophen.
4. PNEUMONIA
INTRODUCTION:
Pneumonia is an inflammatory condition of the lung especially affecting the microscopic air
sacs (alveoli), associated with fever, chest symptoms, and a lack of air space (consolidation) on a
chest X-ray. Pneumonia is typically caused by an infection but there are a number of other
causes. Infectious agents include: bacteria, viruses, fungi, and parasites. Vaccines to prevent
certain types of pneumonia are available. Treatment depends on the underlying cause. Presumed
bacterial pneumonia is treated with antibiotics.
CLASSIFICATION OF PNEUMONIA:
Pneumonia can be classified in several ways. It is most commonly classified by where or how it
was acquired (community-acquired, aspiration, healthcare-associated, hospital-acquired, and
ventilator-associated pneumonia), but may also be classified by the area of lung affected (lobar
pneumonia, bronchial pneumonia and acute interstitial pneumonia), or by the causative
organism. Pneumonia in children may additionally be classified based on signs and symptoms as
non-severe, severe, or very severe.
 On the basis of where or how it was acquired, pneumonia is classified as;
i. Community-Acquired Pneumonia: Community-acquired pneumonia (CAP) occurs
outside of hospitals and other health care settings. Most people get CAP by breathing in
germs (especially while sleeping) that live in the mouth, nose, or throat. CAP is the most
common type of pneumonia. Most cases occur during the winter. About 4 million people
get this form of pneumonia each year. About 1 out of every 5 people who has CAP needs
to be treated in a hospital.
ii. Hospital-Acquired Pneumonia: Some people catch pneumonia during a hospital stay
for another illness. This is called hospital-acquired pneumonia (HAP). You're at higher
risk of getting HAP if you're on a ventilator (a machine that helps you breathe). HAP
tends to be more serious than CAP because you're already sick.
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Health Care-Associated Pneumonia: Patients also may get pneumonia in other health
care settings, such as nursing homes, dialysis centers, and outpatient clinics. This type of
pneumonia is called health care-associated pneumonia.
Aspiration Pneumonia: This type of pneumonia can occur if you inhale food, drink,
vomit, or saliva from your mouth into your lungs. This may happen if something disturbs
your normal gag reflex, such as a brain injury, swallowing problem, or excessive use of
alcohol or drugs. Aspiration pneumonia can cause pus to form in a cavity in the lung.
When this happens, it's called a lung abscess (AB-ses).
Atypical Pneumonia: Several types of bacteria Legionella pneumophila, mycoplasma
pneumonia, and Chlamydophila pneumoniae cause atypical pneumonia, a type of CAP.
Atypical pneumonia is passed from person to person.
HISTORY:
Pneumonia has been a common disease throughout human history. The symptoms were
described by Hippocrates. Maimonides (1135–1204 AD) observed "The basic symptoms that
occur in pneumonia and that are never lacking are as follows: acute fever, sticking pleuritic pain
in the side, short rapid breaths, serrated pulse and cough." This clinical description is quite
similar to those found in modern textbooks, and it reflected the extent of medical knowledge
through the Middle Ages into the 19th century.
Bacteria were first seen in the airways of individuals who died from pneumonia by Edwin Klebs
in 1875. Initial work identifying the two common bacterial causes Streptococcus pneumoniae
and Klebsiella pneumoniae was performed by Carl Friedländer and Albert Fränkel in 1882 and
1884, respectively.
Several developments in the 1900s improved the outcome for those with pneumonia. With the
advent of penicillin and other antibiotics, modern surgical techniques, and intensive care in the
twentieth century, mortality from pneumonia, which had approached 30%, dropped precipitously
in the developed world. Vaccination of infants against Haemophilus influenzae type B began in
1988 and led to a dramatic decline in cases shortly thereafter. Vaccination against Streptococcus
pneumoniae in adults began in 1977, and in children in 2000, resulting in a similar decline.
EPIDEMIOLOGY:
Pneumonia is a common illness affecting approximately 450 million people a year and occurring
in all parts of the world. It is a major cause of death among all age groups resulting in 4 million
deaths (7% of the world's yearly total). Rates are greatest in children less than five, and adults
older than 75 years of age. It occurs about five times more frequently in the developing world
versus the developed world. Viral pneumonia accounts for about 200 million cases. In 2008
pneumonia occurred in approximately 156 million children (151 million in the developing world
and 5 million in the developed world). It resulted in 1.6 million deaths, or 28–34% of all deaths
in those under five years of age, of which 95% occurred in the developing world.
ETIOLOGY:
Pneumonia is due primarily to infections, with less common causes including irritants and the
unknown. Although more than one hundred strains of microorganisms can cause pneumonia,
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only a few are responsible for most cases. The most common types of infectious agents are
viruses and bacteria, with its being less commonly due to fungi or parasites. Mixed infections
with both viruses and bacteria may occur in up to 45% of infections in children and 15% of
infections in adults.
Bacterial cause: Bacteria are the most common cause of
community acquired pneumonia, with Streptococcus
pneumoniae isolated in nearly 50% of cases. Other
commonly isolated bacteria include: Haemophilus
influenzae in 20%, Chlamydophila pneumoniae in 13%,
Mycoplasma pneumoniae in 3%, Staphylococcus aureus,
Moraxella catarrhalis, Legionella pneumophila and gramnegative bacilli.
Risk factors for infection depend on the organism involved. Alcoholism is associated with
Streptococcus pneumoniae, anaerobic organisms, and Mycobacterium tuberculosis, smoking is
associated with Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and
Legionella pneumophila, exposure to bird with Chlamydia psittaci, farm animals with Coxiella
burnetti, aspiration of stomach contents with anaerobes, and cystic fibrosis with Pseudomonas
aeruginosa and Staphylococcus aureus. Streptococcus pneumoniae is more common in the
winter.
Viral Cause: In adults, viruses account for approximately a third of pneumonia cases.
Commonly implicated agents include: rhinoviruses, coronaviruses, influenza virus, respiratory
syncytial virus (RSV), adenovirus, and parainfluenza. Herpes simplex virus is a rare cause of
pneumonia, except in newborns. People with weakened immune systems are at increased risk of
pneumonia caused by cytomegalovirus (CMV).
Fungal cause: The pathophysiology of pneumonia caused by fungi is similar to that of bacterial
pneumonia. Fungal pneumonia is most often caused by Histoplasma capsulatum, blastomyces,
Cryptococcus neoformans, Pneumocystis jiroveci, and Coccidioides immitis. Histoplasmosis is
most common in the Mississippi River basin, and coccidioidomycosis is most common in the
southwestern United States.
Parasites cause: A variety of parasites can affect the lungs. These parasites typically enter the
body through the skin or the mouth. Once inside the body, they travel to the lungs, usually
through the blood. In parasitic pneumonia, as with other kinds of pneumonia, a combination of
cellular destruction and immune response causes disruption of oxygen transportation. One type
of white blood cell, the eosinophil, responds vigorously to parasite infection. Eosinophils in the
lungs can lead to eosinophilic pneumonia, thus complicating the underlying parasitic pneumonia.
The most common parasites causing pneumonia are Toxoplasma gondii, Strongyloides
stercoralis, and Ascariasis.
Idiopathic cause: Idiopathic interstitial pneumonia or noninfectious pneumonia are a class of
diffuse lung diseases. They include: diffuse alveolar damage, organizing pneumonia, nonspecific
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interstitial pneumonia, lymphocytic interstitial pneumonia, desquamative interstitial pneumonia,
respiratory bronchiolitis interstitial lung disease, and usual interstitial pneumonia.
PATHOPHYSIOLOGY:
Pneumonia frequently starts as an upper respiratory tract infection that moves into the lower
respiratory tract.
Viral attack: Viruses invade cells in order to reproduce. Typically, a virus reaches the lungs
when airborne droplets are inhaled through the mouth or nose. Once in the lungs, the virus
invades the cells lining the airways and alveoli. This
invasion often leads to cell death, either from damage to
the cell by the virus or from a protective process called
apoptosis in which the infected cell destroys itself before it
can be used as a conduit for virus reproduction. When the
immune system responds to the viral infection, even more
lung damage occurs. White blood cells, mainly
lymphocytes, activate certain chemical cytokines that
allow fluid to leak into the alveoli. This combination of
cell destruction and fluid-filled alveoli interrupts the
normal transportation of oxygen into the bloodstream. As
well as damaging the lungs, many viruses affect other
organs and thus disrupt many body functions. Viruses can
also make the body more susceptible to other bacterial
infections; in this way bacterial pneumonia can arise as a
co-morbid condition.
Bacterial attack: Bacteria typically enter the lung when airborne droplets are inhaled, but can
also reach the lung through the bloodstream when there is an infection in another part of the
body. Many bacteria live in parts of the upper respiratory tract, such as the nose, mouth, and
sinuses, and can easily be inhaled into the alveoli. Once inside, bacteria may invade the spaces
between cells and between alveoli through connecting pores. This invasion triggers the immune
system to send neutrophils, a type of defensive white blood cell, to the lungs. The neutrophils
engulf and kill the offending organisms, and also release cytokines, causing a general activation
of the immune system. This leads to the fever, chills, and fatigue common in bacterial and fungal
pneumonia. The neutrophils, bacteria, and fluid from surrounding blood vessels fill the alveoli
and interrupt normal oxygen transportation.
COMPLICATIONS:
Pneumonia is more likely to cause complications in older people, smokers and people with heart
failure or lung disease, such as COPD. Pneumonia complications may include:
1. Bacteria in your bloodstream: The smallest airways in your lungs terminate in tiny air sacs
called alveoli, where blood cells exchange carbon dioxide for oxygen. In pneumonia, alveoli
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3.
4.
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contain bacteria that may enter the bloodstream during gas exchange. Infection then spreads
through the bloodstream, potentially causing shock and failure of multiple organs.
Septic shock: Unchecked bacterial growth in the bloodstream can shut down normal
circulation. Blood fills the veins and leaks through the walls of the capillaries, causing
uncontrolled tissue swelling and possibly organ failure, which can lead to death.
Fluid accumulation and infection around your lungs: Sometimes fluid accumulates
between the thin, transparent membrane (pleura) covering your lungs and the membrane that
lines the inner surface of your chest wall - a condition known as pleural effusion. When the
pleurae around your lungs become inflamed (pleurisy), often as a result of pneumonia, fluid
can accumulate and may become infected (empyema).
Lung abscess: Occasionally a cavity containing pus (abscess) forms within the area affected
by pneumonia.
Acute respiratory distress syndrome (ARDS): When pneumonia involves most areas of
both lungs, breathing is difficult and your body doesn't get enough oxygen. Underlying lung
disease of any kind, but especially COPD, makes you more susceptible to ARDS.
SIGNS AND SYMPTOMS:
People with infectious pneumonia often have a productive cough, fever accompanied by shaking
chills, shortness of breath, sharp or stabbing chest pain during deep breaths, confusion, and an
increased respiratory rate. In the elderly, confusion may be the most prominent symptom. The
typical symptoms in children under five are fever, cough, and fast or difficult breathing. Fever,
however, is not very specific, as it occurs in many other common illnesses, and may be absent in
those with severe disease or malnutrition. In addition, a cough is frequently absent in children
less than 2 months old. More severe symptoms may
include: central cyanosis, decreased thirst, convulsions,
persistent vomiting, or a decreased level of
consciousness.
Some causes of pneumonia are associated with classic,
but non-specific, clinical characteristics. Pneumonia
caused by Legionella may occur with abdominal pain,
diarrhea, or confusion, while pneumonia caused by
Streptococcus pneumoniae is associated with rusty
colored sputum, and pneumonia caused by Klebsiella
may have bloody sputum often described as "currant
jelly".
Physical examination may sometimes reveal low blood
pressure, a high heart rate, or a low oxygen saturation.
Examination of the chest may be normal, but may show decreased chest expansion on the
affected side. Harsh breath sounds from the larger airways that are transmitted through the
inflamed lung are termed bronchial breathing, and are heard on auscultation with a stethoscope.
Rales (or crackles) may be heard over the affected area during inspiration. Percussion may be
dulled over the affected lung, and increased, rather than decreased, vocal resonance distinguishes
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pneumonia from a pleural effusion. Struggling to breathe, confusion, and blue-tinged skin are
signs of a medical emergency.
DIAGNOSIS:
Pneumonia is typically diagnosed based on a combination of physical signs and a chest X-ray.
Confirming the underlying cause can be difficult, however, with no definitive test able to
distinguish between bacterial and not-bacterial origin. These are;
a) Breath examinations: A rapid respiratory rate is defined as greater than 60 breaths per
minute in children under 2 months old, 50 breaths per minute in children two months to
one year old, or greater than 40 breaths per minute in children one to five years old. In
children, an increased respiratory rate and lower chest indrawing are more sensitive than
hearing chest crackles with a stethoscope.
b) Other tests: In adults, investigations are in general not needed in mild cases as if all vital
signs and auscultation are normal the risk of pneumonia is very low. In those requiring
admission to a hospital, pulse oximetry, chest radiography, and blood tests including a
complete blood count, serum electrolytes, C-reactive protein, and possibly liver function
tests are recommended.
c) Imaging: A chest radiograph is frequently used in diagnosis. In people with mild disease,
imaging is needed only in those with potential
complications, those who have not improved with
treatment, or those in which the cause in uncertain. If
a person is sufficiently sick to require hospitalization,
a chest radiograph is recommended. Findings do not
always correlate with severity of disease and do not
reliably distinguish between bacterial infection and
viral infection. X-ray signs of bacterial community
acquired pneumonia classically show lung
consolidation of one lung segmental lobe. However, radiographic findings may be
variable, especially in other types of pneumonia. Aspiration pneumonia may present with
bilateral opacities primarily in the bases of the lungs and on the right side. Radiographs of
viral pneumonia cases may appear normal, hyper-inflated, have bilateral patchy areas, or
present similar to bacterial pneumonia with lobar consolidation. A CT scan can give
additional information in indeterminate cases.
d) Bronchoscopy: This diagnostic tool is also used to look inside the lungs airways. The
bronchoscopy picture of the respiratory parts are taken inside the body with the help of a
camera.
e) Microbiology tests: For those not responsive to treatment, sputum culture should be
considered, and culture for Mycobacterium tuberculosis should be carried out in those
with a chronic productive cough. Testing for other specific organisms may be
recommended during outbreaks, for public health reasons. In those who are hospitalized
for severe disease both sputum and blood cultures are recommended. Viral infections can
be confirmed via detection of either the virus or its antigens with culture or polymerase
chain reaction (PCR) among other techniques. With routine microbiological testing a
causative agent is determined in only 15% of cases.
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TREATMENT:
Typically, oral antibiotics, rest, simple analgesics, and fluids suffice for complete resolution.
However, those with other medical conditions, the elderly, or those with significant trouble
breathing may require more advanced care. If the symptoms worsen, the pneumonia does not
improve with home treatment, or complications occur, hospitalization may be required.
Bacterial infection treatment: Antibiotics improve outcomes in those with bacterial
pneumonia. Antibiotic choice depends initially on the characteristics of the person affected, such
as age, underlying health, and the location the infection was acquired. In the UK, empiric
treatment with amoxicillin is recommended as the first line for community-acquired pneumonia,
with doxycycline or clarithromycin as alternatives. In North America, where the "atypical"
forms of community-acquired pneumonia are more common, macrolides (such as azithromycin),
and doxycycline have displaced amoxicillin as first-line outpatient treatment in adults. In
children with mild or moderate symptoms amoxicillin remains the first line. The use of
fluoroquinolones in uncomplicated cases is discouraged due to concerns about side effects and
resistance. Antibiotics recommended for hospital-acquired pneumonia include third- and fourthgeneration cephalosporins, carbapenems, fluoroquinolones, aminoglycosides, and
vancomycin. These antibiotics, often given intravenously, may be used in combination.
Viral infection treatment: Neuraminidase inhibitors may be used to treat viral pneumonia
caused by influenza viruses (influenza A and influenza B). No specific antiviral medications are
recommended for other types of community acquired viral pneumonias including SARS
coronavirus, adenovirus, hantavirus, and parainfluenza virus. Influenza A may be treated with
rimantadine or amantadine, while influenza A or B may be treated with oseltamivir,
zanamivir or peramivir. The use of antibiotics in viral pneumonia is recommended by some
experts as it is impossible to rule out a complicating bacterial infection.
Aspiration pneumonia treatment: In general, aspiration pneumonitis is treated conservatively
with antibiotics indicated only for aspiration pneumonia. The choice of antibiotic will depend on
several factors, including the suspected causative organism and whether pneumonia was acquired
in the community or developed in a hospital setting. Common options include clindamycin, a
combination of a beta-lactam antibiotic and metronidazole, or an aminoglycoside.
Corticosteroids are commonly used in aspiration pneumonia, but there is no evidence to support
their effectiveness.
PREVENTION:
Prevention includes vaccination, environmental measures, and appropriately treating other
diseases.
i.
Vaccination: Vaccination is effective for preventing certain bacterial and viral
pneumonias in both children and adults. Influenza vaccines are modestly effective against
influenza A and B. The Center for Disease Control and Prevention (CDC) recommends
that everyone 6 months and older get yearly vaccination. Vaccinations against
Haemophilus influenzae and Streptococcus pneumoniae have good evidence to support
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their use. Vaccinating children against Streptococcus pneumoniae has also led to a
decreased incidence of these infections in adults, because many adults acquire infections
from children. A vaccine against Streptococcus pneumoniae is also available for adults,
and has been found to decrease the risk of invasive pneumococcal disease.
Environmental control: Reducing indoor air pollution is recommended as is smoking
cessation.
Others: There are several ways to prevent pneumonia in newborn infants. Testing
pregnant women for Group B Streptococcus and Chlamydia trachomatis, and giving
antibiotic treatment, if needed, reduces pneumonia in infants. Suctioning the mouth and
throat of infants with meconium-stained amniotic fluid decreases the rate of aspiration
pneumonia.
5.
TUBERCULOSIS
INTRODUCTION:
Tuberculosis is a common, and in many cases lethal, infectious disease caused by various strains
of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis typically attacks the lungs,
but can also affect other parts of the body. It is spread through the air when people who have an
active TB infection cough, sneeze, or otherwise transmit their saliva through the air. Most
infections are asymptomatic and latent, but about one in 10 latent infections eventually
progresses to active disease which, if left untreated, kills more than 50% of those so infected.
CLASSIFICATION OF TUBERCULOSIS:
Tuberculosis is a contagious disease that affects almost all the important organs of the body.
Clinically, tuberculosis is broadly categorized into four major categories.
i.
ii.
iii.
Primary Tuberculosis: When tuberculosis affects a person who had never been exposed
to the bacterium earlier, the condition is called primary tuberculosis. In this form of
tuberculosis, the source of bacterium is external. Its symptoms are very much similar to
pneumonia. In primary tuberculosis the lymph nodes get affected leading to their
swelling. Lesions are also formed which are removed during treatment. The removal of
the lesion does not indicate bacterial removal as the bacteria may have gone into a
dormant phase and if left untreated, it can cause TB when favourable condition comes.
Secondary Tuberculosis: It is also known as post-primary tuberculosis. This type of
tuberculosis occurs in a person who previously had TB. In primary TB, the bacterium
goes into an inactive phase while in secondary tuberculosis; the bacterium regains its
active mode and causes the symptoms. Secondary tuberculosis is mostly localised to
lungs as oxygen pressure is highest there. Secondary tuberculosis is more infectious than
primary tuberculosis. Secondary TB increases the chance of the infection’s spread to
other organs such as kidneys, heart and brain.
Disseminated Tuberculosis: Disseminated tuberculosis means that the tuberculosis has
infected the entire body system. It is a very rare type of the disease. Disseminated TB
primarily affects the bones of spines, hips, joints and knees, the genital tract of women,
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the urinary tract and even the central nervous system. It infects the cerebrospinal fluids,
the gastrointestinal tract, the adrenal gland, skin of the neck and even the heart.
Miliary Tuberculosis: It is the most severe type of tuberculosis infection. Whole of the
blood stream gets infected with the bacterium. Numerous tiny lesions appear throughout
the body. If the infection reaches bone marrow, it can cause anaemia. The infection in the
blood causes uncontrolled multiplication of white blood cells, thereby leading to
leukaemia-like conditions.
HISTORY:
Tuberculosis has been present in humans since antiquity. The earliest unambiguous detection of
M. tuberculosis involves evidence of the disease in the remains of bison dated to approximately
17,000 years ago. Skeletal remains show prehistoric humans (4000 BC) had TB, and researchers
have found tubercular decay in the spines of Egyptian mummies dating from 3000–2400 BC.
During the years 1838–1845, Dr. John Croghan, the owner of Mammoth Cave, brought a number
of people with tuberculosis into the cave in the hope of curing the disease with the constant
temperature and purity of the cave air; they died within a year. Hermann Brehmer opened the
first TB sanatorium in 1859 in Sokołowsko, Poland.
Albert Calmette and Camille Guérin achieved the first genuine success in immunization against
tuberculosis in 1906, using attenuated bovine-strain tuberculosis. It was called bacillus of
Calmette and Guérin (BCG).
EPIDEMIOLOGY:
One third of the world's population is thought to have been infected with M. tuberculosis, with
new infections occurring at a rate of about one per second. In 2007, there were an estimated 13.7
million chronic active cases globally, while in 2010, there were an estimated 8.8 million new
cases and 1.5 million associated deaths, mostly occurring in developing countries. The absolute
number of tuberculosis cases has been decreasing since 2006, and new cases have decreased
since 2002. The distribution of tuberculosis is not uniform across the globe; about 80% of the
population in many Asian and African countries test positive in tuberculin tests, while only 5–
10% of the United States population tests positive. More people in the developing world contract
tuberculosis because of compromised immunity, largely due to high rates of HIV infection and
the corresponding development of AIDS.
ETIOLOGY:
Some of the main causes of tuberculosis are;
1. Mycobacteria: The main cause of TB is Mycobacterium tuberculosis, a small, aerobic,
nonmotile bacillus. The high lipid content of this pathogen accounts for many of its unique
clinical characteristics. It divides every 16 to 20 hours, which is an extremely slow rate
compared with other bacteria, which usually divide in less than an hour.
The M. tuberculosis complex (MTBC) includes four other TB-causing mycobacteria: M.
bovis, M. africanum, M. canetti, and M. microti. M. africanum is not widespread, but it is a
significant cause of tuberculosis in parts of Africa. M. bovis was once a common cause of
tuberculosis, but the introduction of pasteurized milk has largely eliminated this as a public
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health problem in developed countries. M. canetti is rare and seems to be limited to the Horn
of Africa, although a few cases have been seen in African emigrants. M. microti is also rare
and is mostly seen in immunodeficient people, although the prevalence of this pathogen has
possibly been significantly underestimated. Other known pathogenic mycobacteria include
M. leprae, M. avium, and M. kansasii.
2. Risk factors: A number of factors make people more susceptible to TB infections.
a) The most important risk factor globally is HIV. This is a particular problem in subSaharan Africa, where rates of HIV are high.
b) Tuberculosis is closely linked to both overcrowding and malnutrition, making it one of
the principal diseases of poverty.
c) Chronic lung disease is another significant risk factor - with silicosis increasing the risk
about 30-fold. Those who smoke cigarettes have nearly twice the risk of TB than
nonsmokers.
d) Other disease states can also increase the risk of developing tuberculosis, including
alcoholism, kidney diseases and diabetes mellitus (threefold increase).
e) Certain medications, such as corticosteroids and infliximab (an anti-αTNF monoclonal
antibody) are becoming increasingly important risk factors, especially in the developed
world.
f) There is also a genetic susceptibility for which overall importance is still undefined.
TRANSMISSION:
a) When people with active pulmonary TB cough, sneeze, speak, sing, or spit, they expel
infectious aerosol droplets 0.5 to 5.0 µm in diameter. A single sneeze can release up to
40,000 droplets. Each one of these droplets may transmit the disease, since the infectious
dose of tuberculosis is very low (the inhalation of fewer than 10 bacteria may cause an
infection).
b) People with prolonged, frequent, or close contact with people with TB are at particularly
high risk of becoming infected, with an estimated 22% infection rate. A person with
active but untreated tuberculosis may infect 10–15 (or more) other people per year.
Transmission should only occur from people with active TB, those with latent infection
are not thought to be contagious.
The probability of transmission from one person to another depends upon several factors,
including the number of infectious droplets expelled by the carrier, the effectiveness of
ventilation, the duration of exposure, the virulence of the M. tuberculosis strain, the level of
immunity in the uninfected person, and others.
PATHOPHYSIOLOGY:
Once inhaled, the infectious droplets settle throughout the airways. The majority of the bacilli are
trapped in the upper parts of the airways where the mucus-secreting goblet cells exist. The mucus
produced catches foreign substances, and the cilia on the surface of the cells constantly beat the
mucus and its entrapped particles upward for removal. This system provides the body with an
initial physical defense that prevents infection in most persons exposed to tuberculosis.
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Bacteria in droplets that bypass the mucociliary system and reach the alveoli are quickly
surrounded and engulfed by alveolar macrophages, the most abundant immune effector cells
present in alveolar spaces. These macrophages, the next line of host defense, are part of the
innate immune system and provide an opportunity for the body to destroy the invading
mycobacteria and prevent infection. Macrophages are readily available phagocytic cells that
combat many pathogens without requiring previous exposure to the pathogens. Several
mechanisms and macrophage receptors are involved in uptake of the mycobacteria. The
mycobacterial lipoarabinomannan is a key ligand for a macrophage receptor. The complement
system also plays a role in the phagocytosis of the bacteria. The complement protein C3 binds to
the cell wall and enhances recognition of the mycobacteria by macrophages. Opsonization by C3
is rapid, even in the air spaces of a host with no previous exposure to M tuberculosis. The
subsequent phagocytosis by macrophages initiates a cascade of events that results in either
successful control of the infection, followed by latent tuberculosis, or progression to active
disease, called primary progressive tuberculosis. The outcome is essentially determined by the
quality of the host defenses and the balance that occurs between host defenses and the invading
mycobacteria.
After being ingested by macrophages,
the mycobacteria continue to multiply
slowly, with bacterial cell division
occurring every 25 to 32 hours.
Regardless of whether the infection
becomes controlled or progresses, initial
development involves production of
proteolytic enzymes and cytokines by
macrophages in an attempt to degrade
the bacteria. Released cytokines attract
T lymphocytes to the site, the cells that
constitute cell-mediated immunity.
Macrophages
then
present
mycobacterial antigens on their surface
to the T cells. This initial immune
process continues for 2 to 12 weeks; the
microorganisms continue to grow until
they reach sufficient numbers to fully
elicit the cell-mediated immune
response, which can be detected by a
skin test.
For persons with intact cell-mediated
immunity, the next defensive step is
formation of granulomas around the M
tuberculosis organisms. These nodulartype lesions form from an accumulation
FIGURE: Pathophysiology of tuberculosis: inhalation of bacilli (A),
containment in a granuloma (B), and breakdown of the granuloma in
less immunocompetent individuals (C).
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of activated T lymphocytes and macrophages, which creates a micro-environment that limits
replication and the spread of the mycobacteria. This environment destroys macrophages and
produces early solid necrosis at the center of the lesion; however, the bacilli are able to adapt to
survive. In fact, M tuberculosis organisms can change their phenotypic expression, such as
protein regulation, to enhance survival. By 2 or 3 weeks, the necrotic environment resembles soft
cheese, often referred to caseous necrosis, and is characterized by low oxygen levels, low pH,
and limited nutrients. This condition restricts further growth and establishes latency. Lesions in
persons with an adequate immune system generally undergo fibrosis and calcification,
successfully controlling the infection so that the bacilli are contained in the dormant, healed
lesions. Lesions in persons with less effective immune systems progress to primary progressive
tuberculosis.
For less immunocompetent persons, granuloma formation is initiated yet ultimately is
unsuccessful in containing the bacilli. The necrotic tissue undergoes liquefaction, and the fibrous
wall loses structural integrity. The semiliquid necrotic material can then drain into a bronchus or
nearby blood vessel, leaving an air-filled cavity at the original site. In patients infected with M
tuberculosis, droplets can be coughed up from the bronchus and infect other persons. If discharge
into a vessel occurs, occurrence of extrapulmonary tuberculosis is likely. Bacilli can also drain
into the lymphatic system and collect in the tracheobronchial lymph nodes of the affected lung,
where the organisms can form new caseous granulomas.
COMPLICATIONS:
Tuberculosis is an infectious disease which leads to numerous health complications. It attacks the
body’s immune system by affecting the B cells and T cells of the immune system. Without
treatment, tuberculosis can be fatal. Untreated active disease typically affects your lungs, but it
can spread to other parts of the body through your bloodstream. Examples include:
1. Bones: Spinal pain and joint destruction may result from TB that infects your bones. In
many cases, the ribs are affected.
2. Brain: Tuberculosis in your brain can cause meningitis, a sometimes fatal swelling of the
membranes that cover your brain and spinal cord.
3. Liver or kidneys: Liver and kidneys help filter waste and impurities from your
bloodstream. These functions become impaired if the liver or kidneys are affected by
tuberculosis. Tuberculosis can cause complications in the excretory system leading to
painful urination. Sometimes the person feels uncomfortable during urination. In severe
cases, blood appears in the urine.
4. Heart complications: Tuberculosis can infect the tissues that surround your heart,
causing inflammation and fluid collections that may interfere with your heart's ability to
pump effectively. This condition, called cardiac tamponade, can be fatal. The pumping
action of the heart gets disturbed due to myocardial infection. This increases the chances
of heart attack and strokes.
5. Drug resistance: If tuberculosis is not treated properly, it develops resistance against
drugs or antibiotics. This condition is known as multi-drug resistance tuberculosis. The
reason for this is that the bacterium undergoes mutation, thereby becoming resistant
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against multiple antibiotics. Tuberculosis which has aggravated to this extent takes a long
course of medication to be treated.
6. Lung complications: Untreated tuberculosis causes severe lung complications. The
bacteria can cause permanent damage to the lungs leading to breathing problems. As the
disease becomes severe, the patient notices blood in cough.
7. Eyes: Tuberculosis can affect eyes by damaging the retina. This can hamper the vision
causing blindness.
8. Other complications: Other complications of tuberculosis include loss of appetite, pain
in the chest, recurring fever with chills, sudden weight loss, vomiting and shortness of
breath.
Tuberculosis is not limited to lungs, but it affects other body parts as well. It’s always advisable
to complete the course of tuberculosis treatment as leaving it in the middle makes the bacteria
resistant against antibiotics. These mutated bacteria cause serious health complications. A proper
diagnosis followed by a proper treatment regimen can protect a person from tuberculosis
complications.
SIGNS AND SYMPTOMS:
General signs and symptoms include fever, chills, night sweats, loss of appetite, weight loss, and
fatigue, and significant finger clubbing may also occur.
Pulmonary signs and symptoms: If a tuberculosis infection does become active, it most
commonly involves the lungs (in about 90% of cases). Symptoms may include chest pain and a
prolonged cough producing sputum. About 25% of people may not have any symptoms.
Occasionally, people may cough up blood in small amounts, and in very rare cases, the infection
may erode into the pulmonary artery, resulting in massive bleeding (Rasmussen's aneurysm).
Tuberculosis may become a chronic illness and cause extensive scarring in the upper lobes of the
lungs. The upper lung lobes are more frequently affected by tuberculosis than the lower ones.
The reason for this difference is not entirely clear. It may be due either to better air flow, or to
poor lymph drainage within the upper lungs.
Extrapulmonary signs and symptoms: In 15–20% of active cases, the infection spreads outside
the respiratory organs, causing other kinds of TB. These are collectively denoted as
"extrapulmonary tuberculosis". Extrapulmonary TB occurs more commonly in
immunosuppressed persons and young children. In those with HIV, this occurs in more than 50%
of cases. Notable extrapulmonary infection sites include the pleura (in tuberculous pleurisy), the
central nervous system (in tuberculous meningitis), the lymphatic system (in scrofula of the
neck), the genitourinary system (in urogenital tuberculosis), and the bones and joints (in Pott's
disease of the spine), among others. When it spreads to the bones, it is also known as "osseous
tuberculosis". a form of osteomyelitis. A potentially more serious, widespread form of TB is
called "disseminated" TB, commonly known as miliary tuberculosis. Miliary TB makes up about
10% of extrapulmonary cases.
DIAGNOSIS:
Diagnosis of tuberculosis based on stage of disease, these are;
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Active tuberculosis: Diagnosing active tuberculosis based merely on signs and symptoms is
difficult, as is diagnosing the disease in those who are immunosuppressed. A diagnosis of TB
should, however, be considered in those with signs of lung disease or constitutional symptoms
lasting longer than two weeks. A chest X-ray and multiple sputum cultures for acid-fast bacilli
are typically part of the initial evaluation. Interferon-γ release assays and tuberculin skin tests are
of little use in the developing world.
A definitive diagnosis of TB is made by identifying M. tuberculosis in a clinical sample (e.g.
sputum, pus, or a tissue biopsy). However, the difficult culture process for this slow-growing
organism can take two to six weeks for blood or sputum culture. Thus, treatment is often begun
before cultures are confirmed.
Nucleic acid amplification tests and adenosine deaminase testing may allow rapid diagnosis of
TB. These tests, however, are not routinely recommended, as they rarely alter how a person is
treated. Blood tests to detect antibodies are not specific or sensitive, so they are not
recommended.
CT scan may be done to diagnose TB. It is a painless and non-invasive test, which takes a series
of detailed pictures of different parts of the body that is being examined. A radiologist can see
the images and diagnose if there is an abnormality in the lung that is suggestive of TB infection.
CT scan of other parts such as the brain, kidney or abdomen may be done if TB infection is
suspected in these organs. CT scan can be more informative than a chest X-ray to diagnose TB.
Latent tuberculosis: The Mantoux tuberculin skin test is
often used to screen people at high risk for TB. Those who
have been previously immunized may have a false-positive
test result. The test may be falsely negative in those with
sarcoidosis, Hodgkin's lymphoma, malnutrition, or most
notably, in those who truly do have active tuberculosis.
Interferon gamma release assays (IGRAs), on a blood
sample, are recommended in those who are positive to the
Mantoux test. These are not affected by immunization or most environmental mycobacteria, so
they generate fewer false-positive results. However they are affected by M. szulgai, M. marinum
and M. kansasii. IGRAs may increase sensitivity when used in addition to the skin test but may
be less sensitive than the skin test when used alone.
TREATMENT:
First line Drugs: All first-line anti-tuberculous drug names have a standard three-letter and a
single-letter abbreviation:




Ethambutol is EMB or E,
isoniazid is INH or H,
pyrazinamide is PZA or Z,
rifampicin is RMP or R,
Second line Drugs: There are six classes of second-line drugs (SLDs) used for the treatment of
TB. A drug may be classed as second-line instead of first-line for one of three possible reasons: it
may be less effective than the first-line drugs (e.g., p-aminosalicylic acid); or, it may have toxic
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side-effects (e.g., cycloserine); or it may be unavailable in many developing countries (e.g.,
fluoroquinolones):




aminoglycosides: e.g., amikacin (AMK), kanamycin (KM);
polypeptides: e.g., capreomycin, viomycin, enviomycin;
Fluoroquinolones: e.g., ciprofloxacin (CIP), levofloxacin, moxifloxacin (MXF);
thioamides: e.g. ethionamide, prothionamide
Third line Drugs: These drugs may be considered "third-line drugs" and are listed here either
because they are not very effective (e.g., clarithromycin) or because their efficacy has not been
proven (e.g., linezolid, R207910). Rifabutin is effective, but is not included on the WHO list
because for most developing countries, it is impractically expensive.







rifabutin
macrolides: e.g., clarithromycin (CLR);
linezolid (LZD);
thioacetazone (T);
thioridazine;
arginine;
vitamin D;
Treatment of TB uses antibiotics to kill the bacteria. Effective TB treatment is difficult, due to
the unusual structure and chemical composition of the mycobacterial cell wall, which hinders the
entry of drugs and makes many antibiotics ineffective. The two antibiotics most commonly used
are isoniazid and rifampicin, and treatments can be prolonged, taking several months. Latent TB
treatment usually employs a single antibiotic, while active TB disease is best treated with
combinations of several antibiotics to reduce the risk of the bacteria developing antibiotic
resistance. People with latent infections are also treated to prevent them from progressing to
active TB disease later in life.
Treatment of new onset :
1. First type of Six month regimen: The recommended treatment of new-onset pulmonary
tuberculosis is six months of a combination of antibiotics containing rifampicin, isoniazid,
pyrazinamide and ethambutol for the first two months, and only rifampicin and isoniazid for
the last four months. Where resistance to isoniazid is high, ethambutol may be added for the
last four months as an alternative. This four drug, 6-month regimen is effective even when
the infecting organism is resistant to INH. This recommendation applies to both HIVinfected and uninfected persons. However, in the presence of HIV infection it is critically
important to assess the clinical and bacteriologic response. If there is evidence of a slow or
suboptimal response, therapy should be prolonged as judged on a case by case basis.
2. First type of Six month regimen: A 6-month regimen consisting of isoniazid, rifampin, and
pyrazinamide given for 2 month followed by isoniazid and rifampin for 4 month is the
preferred treatment for patients with fully susceptible organisms who adhere to treatment.
Ethambutol (or streptomycin in children too young to be monitored for visual acuity) should
be included in the initial regimen until the results of drug susceptibility studies are available,
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unless there is little possibility of drug resistance (i.e., there is less than 4% primary
resistance to isoniazid in the community, and the patient has had no previous treatment with
antituberculosis medications, is not from a country with a high prevalence of drug resistance,
and has no known exposure to a drug-resistant case).
3. Nine month regimen: A 9-month regimen of isoniazid and rifampin is acceptable for
persons who cannot or should not take pyrazinamide. Ethambutol (or streptomycin in
children too young to be monitored for visual acuity) should also be included until the results
of drug susceptibility studies are available, unless there is little possibility of drug resistance.
After 2 month, for furtther seven month isoniazid, rifampicin and pyridoxine is continued. If
INH resistance is demonstrated, rifampin and ethambutol should be continued for a minimum
of 12 month.
4. Tweleve month regimen: It is inexpensive and reasonably effective. In Regimen 1, which is
100% effective, includes isoniazid (15mg/kg/day) and pyridoxine (1tablet of 10mg daily). In
regimen 2, which is very cheap and effective upto 90%, includes tablet thiocetazone (150mg
OD) and pridoxine (10mg OD).
5. Four month regimen: A 4-month regimen of isoniazid and rifampin is acceptable therapy
for adults who have active tuberculosis and who are sputum-smear and culture negative, if
there is little possibility of drug resistance.
6. Extrapulmonary tuberculosis treatment: Extrapulmonary tuberculosis should be managed
according to the principles and with the drug regimens outlined for pulmonary tuberculosis,
except for children who have miliary tuberculosis, bone/joint tuberculosis, or tuberculous
meningitis who should receive a minimum of 12 month of therapy.
7. Multiple-drug-resistant tuberculosis (i.e., resistance to at least isoniazid and rifampin)
presents difficult treatment problems. Treatment must be individualized and based on
susceptibility studies. In such cases, consultation with an expert in tuberculosis is
recommended.
8. Directly observed therapy short course (DOTS): In order to improve compliance, special
clinics are used to supervise treatment regimens directly.
9. Children should be managed in essentially the same ways as adults using appropriately
adjusted doses of the drugs. This document addresses specific important differences between
the management of adults and children.
10. The major determinant of the outcome of treatment is patient adherence to the drug regimen.
Careful attention should be paid to measures designed to foster adherence and to ensure that
patients take the drugs as prescribed. The use of fixed drug combinations may enhance
patient adherence and may reduce the risk of inappropriate monotherapy, and it may prevent
the development of secondary drug resistance. For this reason, the use of such fixed drug
combinations is strongly encouraged in adults. Virtually all the treatment regimens may be
given intermittently if directly observed, thus assuring adherence.
11. Latent TB: If you have latent TB, the doctor may prescribe just one or two types of TB
drugs for a few months.
Treatment of Recurrent disease:
If tuberculosis recurs, testing to determine to which antibiotics it is sensitive is important before
determining treatment. If multiple drug-resistant TB (MDR-TB) is detected, treatment with at
least four effective antibiotics for 18 to 24 months is recommended.
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PREVENTION:
The only type of tuberculosis that is contagious is the active variety, when it affects the lungs. So
if you can prevent your latent tuberculosis from becoming active, you won't transmit tuberculosis
to anyone else. Following are preventions guidelines, these are;
Protect your family and friends: If you have active TB, keep your germs to yourself. It
generally takes a few weeks of treatment with TB medications before you're not contagious
anymore. Follow these tips to help keep your friends and family from getting sick:
i.
ii.
iii.
iv.
Stay home. Don't go to work or school or sleep in a room with other people during the
first few weeks of treatment for active tuberculosis.
Ventilate the room. Tuberculosis germs spread more easily in small closed spaces where
air doesn't move. If it's not too cold outdoors, open the windows and use a fan to blow
indoor air outside.
Cover your mouth. Use a tissue to cover your mouth anytime you laugh, sneeze or
cough. Put the dirty tissue in a bag, seal it and throw it away.
Wear a mask. Wearing a surgical mask when you're around other people during the first
three weeks of treatment may help lessen the risk of transmission.
Avoid contact with infected person: A person with active TB is infective. They become noninfective after a few weeks of treatment. Avoid close contact with a person, who is diagnosed
with TB, until he or she becomes non-infective.
Finish your entire course of medication: This is the most important step you can take to
protect yourself and others from tuberculosis. When you stop treatment early or skip doses, TB
bacteria have a chance to develop mutations that allow them to survive the most potent TB
drugs. The resulting drug-resistant strains are much more deadly and difficult to treat.
Vaccinations: In countries where tuberculosis is more common, infants are vaccinated with
bacillus Calmette-Guerin (BCG) vaccine because it can prevent severe tuberculosis in children.
The BCG vaccine is not recommended for general use in the United States because it isn't very
effective in adults and it causes a false-positive result on a TB skin test. Researchers are working
on developing a more effective TB vaccine. Tuberculosis prevention and control efforts
primarily rely on the vaccination of infants and the detection and appropriate treatment of active
cases. The World Health Organization has achieved some success with improved treatment
regimens, and a small decrease in case numbers.
The only currently available vaccine as of 2011 is bacillus Calmette–Guérin (BCG) which, while
it is effective against disseminated disease in childhood, confers inconsistent protection against
contracting pulmonary TB. Nevertheless, it is the most widely used vaccine worldwide, with
more than 90% of all children being vaccinated. However, the immunity it induces decreases
after about ten years. As tuberculosis is uncommon in most of Canada, the United Kingdom, and
the United States, BCG is only administered to people at high risk. A number of new vaccines
are currently in development.
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6. ANEMIA
INTRODUCTION:
Anemia is a decrease in number of red blood cells (RBCs) or less than the normal quantity of
hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each
hemoglobin molecule due to deformity or lack in numerical development as in some other types
of hemoglobin deficiency. Because hemoglobin (found inside RBCs) normally carries oxygen
from the lungs to the tissues, anemia leads to hypoxia (lack of oxygen) in organs. Since all
human cells depend on oxygen for survival, varying degrees of anemia can have a wide range of
clinical consequences.
CLASSIFICATION:

In general, there are three major types of anemia, classified according to the size of the
red blood cells:
1. If the red blood cells are smaller than normal, (under 80 fl), this is called microcytic
anemia. The major causes of this type are iron deficiency (low level iron) anemia and
thalassemia (inherited disorders of hemoglobin).
2. If the red blood cells size are normal (80–100 fl) in size (but low in number), this is
called normocytic anemia, such as anemia that accompanies chronic disease or anemia
related to kidney disease.
3. If red blood cells are larger than normal(over 100 fl), then it is called macrocytic
anemia. Major causes of this type are pernicious anemia and anemia related to
alcoholism.
 On the basis of etiology, the anemia is divided into five types, these are;
1. Hemorrhagic anemia: Anemia due to hemorrhage is known as hemorrhagic anemia. It
occure both in acute and chronic hemorrhagic conditions. Hemorrhage occurs in
conditions like accident, ulcer and hemophilia.
2. Hemolytic anemia: Hemolytic anemia occurs because of excess destruction of RBCs. It
occurs in two inherited conditions called sickle cell anemia and thalassemia.
3. Nutrition defeciency anemia: It is due to the defeciency of iron, proteins and vitamins
like C, B12 and folic acid. e.g. iron defeciency anemia, protein defeciency anemia,
pernicious anemia, megaloblastic anemia etc.
4. Aplastic anemia: It is due to the disorder of red bone marrow. The red bone marrow is
reduced and replaced by fatty tissues. It occurs in conditions like repeated exposure to Xray or gamma ray radiation and by the presence of bacterial toxins, quinine, radium etc.
5. Anemia of chronic diseases: This type of anemia develops after few months of sustained
disease. Its causes are non-infectioous inflammatory disease and tuberculosis etc.
EPIDEMIOLOGY:
Anemia is a common, multifactorial condition. World wide, over 50% of pregnant women and
over 40% of infants are anaemic. The World Health Organization (WHO) definition of anemia
(hemoglobin concentration <12 g/dL in women and <13 g/dL in men) is most often used in
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epidemiologic studies of older adults. More than 10% of community-dwelling adults age 65
years and older has WHO-defined anemia. After age 50 years, prevalence of anemia increases
with advancing age and exceeds 20% in those 85 years and older. In nursing homes, anemia is
present in 48% to 63% of residents. Incidence of anemia in older adults is not well characterized.
Among older adults with anemia, approximately one third have evidence of iron, folate, and/or
vitamin B(12) deficiency, another third have renal insufficiency and/or chronic inflammation,
and the remaining third have anemia that is unexplained. Several studies demonstrate that anemia
is associated with poorer survival in older adults. This review details the distribution and
consequences of anemia in older adults and identifies future epidemiologic research needs.
ETIOLOGY:
Many medical conditions cause anemia. Common causes of anemia include the following:
1. Anemia from active bleeding: Loss of blood through heavy menstrual bleeding or,
wounds can cause anemia. Gastrointestinal ulcers or cancers such as cancer of the colon
may slowly ooze blood and can also cause anemia.
2. Iron deficiency anemia: The bone marrow needs iron to make red blood cells. Iron plays
an important role in the proper structure of the hemoglobin molecule. If iron intake is
limited or inadequate due to poor dietary intake, anemia may occur as a result. This is
called iron deficiency anemia. Iron deficiency anemia can also occur when there are
stomach ulcers or other sources of slow, chronic bleeding (colon cancer, uterine cancer,
intestinal polyps, hemorrhoids, etc). In these kinds of scenarios, because of ongoing,
chronic slow blood loss, iron is also lost from the body (as a part of blood) at a higher
rate than normal and can result in iron deficiency anemia.
3. Anemia of chronic disease: Any long-term medical condition can lead to anemia. The
exact mechanism of this process in unknown, but any long-standing and ongoing medical
condition such as a chronic infection or a cancer may cause this type of anemia.
4. Anemia related to kidney disease: The kidneys release a hormone called the
erythropoietin that helps the bone marrow make red blood cells. In people with chronic
(long-standing) kidney disease, the production of this hormone is diminished, and this in
turn diminishes the production of red blood cells, causing anemia. This is called anemia
related to chronic kidney disease.
5. Anemia related to pregnancy: Water weight gain during pregnancy dilutes the blood,
which may be reflected as anemia.
6. Anemia related to poor nutrition: Vitamins and minerals are required to make red
blood cells. In addition to iron, vitamin B12 and folate are required for the proper
production of hemoglobin. Deficiency in any of these may cause anemia because of
inadequate production of red blood cells. Poor dietary intake is an important cause of low
folate and low vitamin B12 levels. Strict vegetarians who do not take sufficient vitamins
are at risk to develop vitamin B12 deficiency.
7. Pernicious Anemia: There also may be a problem in the stomach or the intestines
leading to poor absorption of vitamin B12. This may lead to anemia because of vitamin
B12 deficiency known as pernicious anemia.
8. Sickle cell anemia: In some individuals, the problem may be related to production of
abnormal hemoglobin molecules. In this condition the hemoglobin problem is qualitative,
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or functional. Abnormal hemoglobin molecules may cause problems in the integrity of
the red blood cell structure and they may become crescent-shaped (sickle cells). There are
different types of sickle call anemia with different severity levels. This is typically
hereditary and is more common in those of African, Middle Eastern, and Mediterranean
ancestry.
9. Thalassemia: This is another group of hemoglobin-related causes of anemia. There are
many types of thalassemia, which vary in severity from mild (thalassemia minor) to
severe (thalassemia major). These are also hereditary, but they cause quantitative
hemoglobin abnormalities, meaning an insufficient amount of the correct hemoglobin
type molecules is made.
10. Alcoholism: Poor nutrition and deficiencies of vitamins and minerals are associated with
alcoholism. Alcohol itself may also be toxic to the bone marrow and may slow down red
blood cell production. The combination of these factors may lead to anemia in alcoholics.
11. Bone marrow-related anemia: Anemia may be related to diseases involving the bone
marrow. Some blood cancers such as leukemia or lymphomas can alter the production of
red blood cells and result in anemia. Other processes may be related to a cancer from
another organ spreading to the bone marrow.
12. Aplastic anemia: Occasionally some viral infections may severely affect the bone
marrow and significantly diminish production of all blood cells. Chemotherapy (cancer
medications) and some other medications may pose the same problems.
13. Hemolytic anemia: The normal red blood cell shape is important for its function.
Hemolytic anemia is a type of anemia in which the red blood cells rupture (known as
hemolysis) and become dysfunctional. This could happen due to a variety of reasons.
Some forms of hemolytic anemia can be hereditary with constant destruction and rapid
reproduction of red blood cells (for example, as in hereditary spherocytosis, hereditary
elliptocytosis, and glucose-6-phosphate dehydrogenase or G6GD deficiency) . This type
of destruction may also happen to normal red blood cells in certain conditions, for
example, with abnormal heart valves damaging the blood cells or certain medications that
disrupt the red blood cell structure.
14. Anemia related to medications: Many common medications can occasionally cause
anemia as a side effect in some individuals. The mechanisms by which medications can
cause anemia are numerous (hemolysis, bone marrow toxicity) and are specific to the
medication. Medications that most frequently cause anemia are chemotherapy drugs used
to treat cancers. Other common medications that can cause anemia include some seizure
medications, transplant medications, HIV medications, some malaria medications, some
antibiotics (penicillin, chloramphenicol), antifungal medications, and antihistamines.
15. Other less common causes of anemia include thyroid problems, cancers, liver disease,
autoimmune diseases (lupus), paroxysmal nocturnal hemoglobinuria (PNH), lead
poisoning, AIDS, malaria, viral hepatitis, mononucleosis, parasitic infections
(hookworm), bleeding disorders, and insecticide exposure.
PATHOPHYSIOLOGY:
Anemia can also be defined physiologically by the degree of impairment of tissue oxygenation.
Oxygen supply to tissues is controlled by a well-balanced mechanism that depends on the
relative rate of oxygen supply and demand. Tissue oxygen delivery is dependent on the
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hemoglobin concentration, oxygen saturation and oxygen affinity, the degree and rate of change
in blood volume, and the capacity for the cardiovascular and pulmonary systems to compensate.
These, in turn, determine the clinical manifestations of anemia, on which the decision to
transfuse should ultimately be based. Tissue oxygen delivery is also the major controlling factor
of erythropoiesis through the synthesis and release of erythropoietin (EPO) by the proximal
tubular cells or the peritubular interstitial cells in the kidney. EPO synthesis is governed by the
activation of hypoxia inducible factor-1 (HIF-1), which controls the metabolic responses of
multiple gene products to hypoxia. HIF-1 binds and activates the hypoxia-responsive
transcriptional enhancer in the erythropoietin gene regulatory region that upregulates
erythropoietin expression. Erythropoietin stimulates erythroid precursor cells (CFU-E [colonyforming units erythroid]), leading to increased proliferation and shortening of their maturation
time. The marrow responds to increased erythropoietin maximally in 4 to 7 days if enough iron is
available. Erythropoiesis can be increased by as much as a factor of 8. Typical of an endocrine
loop feedback mechanism, there is an inverse relation between the hemoglobin and
erythropoietin levels measured in the blood. Although this relation holds true in simple iron
deficiency, it is somewhat distorted in the anemia associated with inflammation or chronic
disease, in which there may be a blunted erythropoietin response. This has made prediction of
the hemoglobin response to treatment with exogenous erythropoietin unpredictable, except in
limited circumstances.
COMPLICATIONS:
Most cases of anemia are mild, including those that occur as a result of chronic disease.
Nevertheless, even mild anemia can reduce oxygen transport in the blood, causing fatigue and a
diminished physical capacity. Moderate-to-severe iron-deficiency anemia is known to reduce
endurance. Because a reduction in red blood cells decreases the ability to absorb oxygen from the
lungs, serious problems can occur in prolonged and severe anemia that is not treated. Anemia
can lead to secondary organ dysfunction or damage, including heart arrhythmia and heart failure.
Certain inherited forms of anemia, including thalassemia major, pernicious anemia, and sicklecell anemia, can be life threatening. Thalassemia major and sickle-cell anemia affect children
and are particularly devastating. The different complications are;
i.
ii.
iii.
iv.
v.
Severe fatigue. When anemia is severe enough, you may be so tired that you can't
complete everyday tasks. You may be too exhausted to work or play.
Heart problems. Anemia can lead to a rapid or irregular heartbeat. Your heart must
pump more blood to compensate for the lack of oxygen in the blood when you're anemic.
This can even lead to congestive heart failure.
Death. Some inherited anemias, such as sickle cell anemia, can be serious and lead to
life-threatening complications. Losing a lot of blood quickly results in acute, severe
anemia and can be fatal.
Effects of Anemia in Pregnant Women: Pregnant women with significant anemia may
have an increased risk for poor pregnancy outcomes, particularly if they are anemic in the
first trimester.
Complications from Anemia in Children and Adolescents: In children, severe anemia
can impair growth and motor and mental development. Children may exhibit a shortened
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attention span and decreased alertness. Children with severe iron-deficiency anemia may
also have an increased risk for stroke.
Effects of Anemia in the Elderly: Anemia is common in older people and can have
significantly more severe complications than anemia in younger adults. Effects of anemia
in the elderly include decreased strength and increased risk for falls. Anemia may have
adverse effects on the heart and increase the severity of cardiac conditions, including
reducing survival rates from heart failure and heart attacks. Even mild anemia may
possibly lead to cognitive impairment or worsen existing dementia.
Effects of Vitamin B12 Deficiencies and Pernicious Anemia: In addition to anemia,
vitamin B12 deficiency can cause neurologic damage, which can be irreversible if it
continues for long periods without treatment.
Anemia in Patients with Cancer: Anemia is particularly serious in cancer patients. In
people with many common cancers, the presence of anemia is associated with a shorter
survival time.
Anemia in Patients with Kidney Disease: Anemia is associated with higher mortality
rates and possibly heart disease in patients with kidney disease.
Anemia in Patients with Heart Failure: The combination of anemia and heart failure
can increase the risk of hospitalization or death by 30 - 60%. Patients with heart failure
whose hemoglobin levels decline do worse than patients with stable levels.
Effects of Excess Iron: Patients with certain types of anemia require frequent blood
transfusions. These transfusions can cause iron overload.
SIGNS AND SYMPTOMS
Because a low red blood cell count decreases oxygen delivery to every tissue in the body, anemia
may cause a variety of signs and symptoms. It can also make almost any other underlying
medical condition worse. If anemia is mild, it may not cause any symptoms. If anemia is slowly
ongoing (chronic), the body may adapt and compensate for the change; in this case there may not
be any symptoms until the anemia becomes more severe. Symptoms of anemia may include the
following:
i. Fatigue
ii. Decreased energy
iii. Weakness
iv.
Shortness of breath
v. Lightheadedness
vi.
Palpitations (feeling of the heart racing or beating irregularly)
vii.
Looking pale
Symptoms of severe anemia may include:
 Chest pain, angina, or heart attack
 Dizziness
 Fainting or passing out
 Rapid heart rate
Some of the signs that may indicate anemia in an individual may include:
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Change in stool color, including black and tarry stools (sticky and foul smelling),
maroon-colored, or visibly bloody stools if the anemia is due to blood loss through the
gastrointestinal tract.
Rapid heart rate
Low blood pressure
Rapid breathing
Pale or cold skin
Yellow skin called jaundice if anemia is due to red blood cell breakdown
Heart murmur
Enlargement of the spleen with certain causes of anemia
Chronic anemia may result in behavioral disturbances in children as a direct result of impaired
neurological development in infants, and reduced scholastic performance in children of school
age. Restless legs syndrome is more common in those with iron-deficiency anemia.
DIAGNOSIS:
Doctors can easily detect anemia by drawing a blood sample for a complete blood count. Based
on the results of the test and thorough evaluation of the patient, the doctor may order more tests
to determine the exact cause of anemia. The complete blood count may be done as part of a
routine general check-up or based upon the presence of signs and symptoms that can be related
to anemia. The different guidelines for diagnosis are;
1.
Physical examination: Physical examination play a crucial role in diagnosing causes of
anemia. While performing a complete physical examination, the physician may particularly
focus on general appearance (signs of fatigue, paleness), jaundice (yellow skin and eyes),
paleness of the nail beds, enlarged spleen (splenomegaly) or liver (hepatomegaly), heart
sounds, and lymph nodes.
2.
Medication and disease history: Some of the important features in medical history cover
questions about family history, previous personal history of anemia or other chronic
conditions, medications, color of stool and urine, bleeding problems, and occupation and
social habits (such as alcohol intake).
3.
Laboratory tests: Because anemia is only a symptom of another disease, doctors will want
to determine what condition is causing the anemia. Some people may need many additional
tests, and others may need very few. Doctors also take into consideration the severity of the
anemia when deciding the tests to order. When a person has severe anemia, the cause must
be determined rapidly so that it can be treated appropriately. Lab tests for anemia may
include the following:
i. Complete blood count (CBC): Determines the severity and type of anemia (microcytic
anemia or small sized red blood cells, normocytic anemia or normal sized red blood cells,
or macrocytic anemia or large sized red blood cells) and is typically the first test ordered.
Information about other blood cells (white cells and platelets) are also included in the
CBC report. The severity of anemia is categorized by the following hemoglobin
concentration ranges:
 Mild anemia is considered when hemoglobin is between 9.5 - 13.0 g/dL.
 Moderate anemia is considered when hemoglobin is between 8.0 - 9.5 g/dL
 Severe anemia is considered for hemoglobin concentrations below 8.0 g/dL
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iii.
iv.
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Stool hemoglobin test: Tests for blood in stool which may detect bleeding from the
stomach or the intestines.
Peripheral blood smear: Looks at the red blood cells under a microscope to determine
the size, shape, number, and color as well as evaluate other cells in the blood.
Iron level: An iron level may tell the doctor whether anemia may be related to iron
deficiency or not. This test is usually accompanied by other tests that measure the body's
iron storage capacity, such as transferrin level and ferritin level.
Transferrin level: Evaluates a protein that carries iron around the body.
Ferritin: Evaluates at the total iron available in the body.
Folate: A vitamin needed to produce red blood cells, which is low in people with poor
eating habits.
Vitamin B12: A vitamin needed to produce red blood cells, low in people with poor
eating habits or in pernicious anemia.
Bilirubin: Useful to determine if the red blood cells are being destroyed within the body
which may be a sign of hemolytic anemia.
Lead level: Lead toxicity used to be one of the more common causes of anemia in
children.
Hemoglobin electrophoresis: Sometimes used when a person has a family history of
anemia; this test provides information on sickle cell anemia or thalassemia.
Reticulocyte count: A reticulocyte count is a quantitative measure of the bone marrow's
production of new red blood cells. The reticulocyte production index is a calculation of
the ratio between the level of anemia and the extent to which the reticulocyte count has
risen in response. If the degree of anemia is significant, even a "normal" reticulocyte
count actually may reflect an inadequate response.
Liver function tests: A common test to determine how the liver is working, which may
give a clue to other underlying disease causing anemia.
Kidney function test: A test that is very routine and can help determine whether any
kidney dysfunction exists.
Bone marrow biopsy: Evaluates production of red blood cells and may be done when a
bone marrow problem is suspected.
TREATMENTS:
Treatments for anemia depend on severity and cause. These are;
1. Iron deficiency anemia. This form of anemia is treated with changes in your diet and
iron supplements. If the underlying cause of iron deficiency is loss of blood other than
from menstruation, the source of the bleeding must be located and stopped. This may
involve surgery.
2. Vitamin deficiency anemias. Folic acid deficiency anemia is treated with folic acid
supplements. If your digestive system has trouble absorbing vitamin B-12 from the food
you eat, you may receive vitamin B-12 injections.
3. Anemia of chronic disease. There's no specific treatment for this type of anemia.
Doctors focus on treating the underlying disease. If symptoms become severe, a blood
transfusion or injections of synthetic erythropoietin, a hormone normally produced by
your kidneys, may help stimulate red blood cell production and ease fatigue.
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4. Aplastic anemia. Treatment for this anemia may include blood transfusions to boost
levels of red blood cells. You may need a bone marrow transplant if your bone marrow is
diseased and can't make healthy blood cells.
5. Anemias associated with bone marrow disease. Treatment of these various diseases
can range from simple medication to chemotherapy to bone marrow transplantation.
6. Hemolytic anemias. Managing hemolytic anemias includes avoiding suspect
medications, treating related infections and taking drugs that suppress your immune
system, which may be attacking your red blood cells. Short courses of treatment with
steroids or immune suppressant medications can help suppress your immune system's
attack on your red blood cells. Depending on the severity of your anemia, a blood
transfusion or plasmapheresis may be necessary. Plasmapheresis is a type of bloodfiltering procedure.
7. Sickle cell anemia. Treatment for this anemia may include the administration of oxygen,
pain-relieving drugs, and oral and intravenous fluids to reduce pain and prevent
complications. Doctors may also recommend blood transfusions, folic acid supplements
and antibiotics. A bone marrow transplant may be an effective treatment in some
circumstances. A cancer drug called hydroxyurea (Droxia, Hydrea) also is used.
Medications For Anemia: Medications and treatments that correct the common underlying
causes of anemia include the following:
i. Iron (Fe): Iron may be taken during pregnancy and when iron levels are low. It is
important to determine the cause of iron deficiency and treat it properly.
Oral Iron: Iron deficiency from nutritional causes is rare in men and postmenopausal
women. The diagnosis of iron deficiency mandates a search for potential sources of loss,
such as gastrointestinal bleeding from ulcers or colon cancer. Mild to moderate irondeficiency anemia is treated by oral iron supplementation with ferrous sulfate, ferrous
fumarate, or ferrous gluconate. When taking iron supplements, stomach upset and/or
darkening of the feces are commonly experienced. Vitamin C aids in the body's ability to
absorb iron, so taking oral iron supplements with orange juice is of benefit. In anemias of
chronic disease, associated with chemotherapy, or associated with renal disease, some
clinicians prescribe recombinant erythropoietin or epoetin alfa, to stimulate RBC
production.
Parenteral Iron: In cases where oral iron has either proven ineffective, would be too
slow (for example, pre-operatively) or where absorption is impeded (for example in cases
of inflammation), parenteral iron can be used. The body can absorb up to 6 mg iron daily
from the gastrointestinal tract. In many cases the patient has a deficit of over 1,000 mg of
iron which would require several months to replace. This can be given concurrently with
erythropoietin to ensure sufficient iron for increased rates of Erythropoiesis.
ii.
iii.
Vitamin Supplements: This may replace folate and vitamin B12 in people with poor
eating habits. In people with pernicious anemia who are unable to absorb sufficient
amounts of vitamin B12, monthly injections of vitamin B12 are commonly used to
replete the vitamin B 12 levels and correct the anemia.
Epoetin alfa (Procrit or Epogen) injection: This can be used to increase red blood cell
production in people with kidney problems. The production of erythropoietin is reduced
in people with advanced kidney disease, as described earlier.
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v.
vi.
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Alcohol stopage: If alcohol is the cause of anemia, then in addition to taking vitamins
and maintaining adequate nutrition, alcohol consumption needs to be stopped.
Blood transfusions: Doctors attempt to avoid blood transfusion in general, since
multiple lines of evidence point to increased adverse patient clinical outcomes with more
intensive transfusion strategies. The physiological principle that reduction of oxygen
delivery associated with anemia leads to adverse clinical outcomes is balanced by the
finding that transfusion does not necessarily mitigate these adverse clinical outcomes. In
severe, acute bleeding, transfusions of donated blood are often lifesaving. Improvements
in battlefield casualty survival are attributable, at least in part, to the recent improvements
in blood banking and transfusion techniques. Transfusion of the stable but anemic
hospitalized patient has been the subject of numerous clinical trials.
Corticosteroids supplimentation: Where the destruction of RBC’s occur,
corticosteroids supplimentation is helpful.
Hyperbaric oxygen: Treatment of exceptional blood loss (anemia) is recognized as an
indication for hyperbaric oxygen (HBO) by the Undersea and Hyperbaric Medical
Society. The use of HBO is indicated when oxygen delivery to tissue is not sufficient in
patients who cannot be given blood transfusions for medical or religious reasons. HBO
may be used for medical reasons when threat of blood product incompatibility or concern
for transmissible disease are factors. The beliefs of some religions (ex: Jehovah's
Witnesses) may require they use the HBO method.
PREVENTIONS:
Some common forms of anemia are most easily prevented by eating a healthy diet and limiting
alcohol use. All types of anemia are best avoided by seeing a doctor regularly and when
problems arise. In the elderly, routine blood work ordered by the doctor, even if there are no
symptoms, may detect anemia and prompt the doctor to look for the underlying causes. The
different prevention guidelines are;
Choose a vitamin-rich diet: Many types of anemia can't be prevented. However, you can help
avoid iron deficiency anemia and vitamin deficiency anemias by choosing a diet that includes a
variety of vitamins and nutrients, including:
 Iron. Iron-rich foods include beef and other meats, beans, lentils, iron-fortified cereals,
dark green leafy vegetables and dried fruit.
 Folate. This nutrient, and its synthetic form, folic acid, can be found in citrus fruits and
juices, bananas, dark green leafy vegetables, legumes and fortified breads, cereals and
pasta.
 Vitamin B-12. This vitamin is found naturally in meat and dairy products. It's also added
to some cereals and soy products, such as soy milk.
 Vitamin C. Foods containing vitamin C, such as citrus fruits, melons and berries, help
increase iron absorption.
Consider genetic counseling if you have a family history of anemia: If you have a family
history of an inherited anemia, such as sickle cell anemia, talk to your doctor and possibly a
genetic counselor about your risk and what risks you may pass on to your children.
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7. PEPTIC ULCER
INTRODUCTION:
A peptic ulcer, also known as peptic ulcer disease, is a break in the inner lining of the
esophagus, stomach, or duodenum. A peptic ulcer of the stomach is called a gastric ulcer; of the
duodenum, a duodenal ulcer; and of the esophagus, an esophageal ulcer. Peptic ulcers occur
when the lining of these organs is corroded by the acidic digestive (peptic) juices which are
secreted by the cells of the stomach. A peptic ulcer differs from an erosion because it extends
deeper into the lining of the esophagus, stomach, or duodenum and excites more of an
inflammatory reaction from the tissues that are eroded. It is defined as mucosal erosions equal to
or greater than 0.5 cm. As many as 70–90% of such ulcers are associated with Helicobacter
pylori, a spiral-shaped bacterium that lives in the acidic environment of the stomach; however,
only 40% of those cases go to a doctor. Ulcers can also be caused or worsened by drugs such as
aspirin, ibuprofen, and other NSAIDs.
CLASSIFICATION:

On the of region/location, ulcer are;
1.
2.
3.
4.

Duodenum (called duodenal ulcer).
Oesophagus (called esophageal ulcer)
Stomach (called gastric ulcer)
Meckel's diverticulum (called Meckel's diverticulum ulcer; is very tender with
palpation)
Modified Johnson Classification of peptic ulcers is on the basis of type, these are;
1. Type I: Ulcer along the body of the stomach, most often along the lesser curve at
incisura angularis along the locus minoris resistantiae.
2. Type II: Ulcer in the body in combination with duodenal ulcers. Associated with acid
oversecretion.
3. Type III: In the pyloric channel within 3 cm of pylorus. Associated with acid
oversecretion.
4. Type IV: Proximal gastroesophageal ulcer
5. Type V: Can occur throughout the stomach. Associated with chronic NSAID use
(such as aspirin).
HISTORY:
John Lykoudis, a general practitioner in Greece, treated patients for peptic ulcer disease with
antibiotics, beginning in 1958, long before it was commonly recognized that bacteria were a
dominant cause for the disease. Helicobacter pylori was rediscovered in 1982 by two Australian
scientists, Robin Warren and Barry J. Marshall as a causative factor for ulcers. In their original
paper, Warren and Marshall contended that most gastric ulcers and gastritis were caused by
colonization with this bacterium, not by stress or spicy food as had been assumed before. In
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1997, the Centers for Disease Control and Prevention, with other government agencies, academic
institutions, and industry, launched a national education campaign to inform health care
providers and consumers about the link between H. pylori and ulcers. This campaign reinforced
the news that ulcers are a curable infection, and that health can be greatly improved and money
saved by disseminating information about H. pylori. Some believed that mastic gum, a tree resin
extract, actively eliminates the H. pylori bacteria. However, multiple subsequent studies have
found no effect of using mastic gum on reducing H. pylori levels.
EPIDEMIOLOGY:
The lifetime risk for developing a peptic ulcer is approximately 10%. In Western countries the
prevalence of Helicobacter pylori infections roughly matches age (i.e., 20% at age 20, 30% at
age 30, 80% at age 80 etc.). Prevalence is higher in third world countries where it is estimated at
about 70% of the population, whereas developed countries show a maximum of 40% ratio.
Overall, H. pylori infections show a worldwide decrease, more so in developped countries.
Transmission is by food, contaminated groundwater, and through human saliva (such as from
kissing or sharing food utensils).
Peptic ulcer disease had a tremendous effect on morbidity and mortality until the last decades of
the 20th century, when epidemiological trends started to point to an impressive fall in its
incidence.The reason that the rates of peptic ulcer disease decreased is thought to be the
development of new effective medication and acid suppressants and the discovery of the cause of
the condition, H. pylori. In the United States about 4 million people have active peptic ulcers and
about 350,000 new cases are diagnosed each year. Four times as many duodenal ulcers as gastric
ulcers are diagnosed. Approximately 3,000 deaths per year in the United States are due to
duodenal ulcer and 3,000 to gastric ulcer.
ETIOLOGY:
These are;
1. Helicobacter Pylori: A major causative factor (60% of gastric and up to 90% of duodenal
ulcers) is chronic inflammation due to Helicobacter pylori that colonizes the antral mucosa.
The immune system is unable to clear the infection, despite the appearance of antibodies.
Thus, the bacterium can cause a chronic active gastritis (type B gastritis), resulting in a
defect in the regulation of gastrin production by that part of the stomach, and gastrin
secretion can either be increased, or as in most cases, decreased, resulting in hypo- or
achlorhydria. Gastrin stimulates the production of gastric acid by parietal cells. In H. pylori
colonization responses to increased gastrin, the increase in acid can contribute to the erosion
of the mucosa and therefore ulcer formation.
2. NSAIDs: Another major cause is the use of NSAIDs. The gastric mucosa protects itself
from gastric acid with a layer of mucus, the secretion of which is stimulated by certain
prostaglandins. NSAIDs block the function of cyclooxygenase 1 (cox-1), which is essential
for the production of these prostaglandins. COX-2 selective anti-inflammatories (such as
celecoxib or the since withdrawn rofecoxib) preferentially inhibit cox-2, which is less
essential in the gastric mucosa, and roughly halve the risk of NSAID-related gastric
ulceration. The incidence of duodenal ulcers has dropped significantly during the last 30
years, while the incidence of gastric ulcers has shown a small increase, mainly caused by the
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widespread use of NSAIDs. The drop in incidence is considered to be a cohort-phenomenon
independent of the progress in treatment of the disease. The cohort-phenomenon is probably
explained by improved standards of living which has lowered the incidence of H. pylori
infections.
3. Stress: Researchers also continue to look at stress as a possible cause, or at least
complication, in the development of ulcers. Burns and head trauma, however, can lead to
physiologic stress ulcers, which are reported in many patients who are on mechanical
ventilation. An expert panel convened by the Academy of Behavioral Medicine Research
concluded that ulcers are not purely an infectious disease and that psychological factors do
play a significant role. Researchers are examining how stress might promote H. pylori
infection. For example, Helicobacter pylori thrives in an acidic environment, and stress has
been demonstrated to cause the production of excess stomach acid. This was supported by a
study on mice showing that both long-term water-immersion-restraint stress and H. pylori
infection were independently associated with the development of peptic ulcers.
4. Other factors: Some studies have found correlations between smoking and ulcer formation,
others have been more specific in exploring the risks involved and have found that smoking
by itself may not be much of a risk factor unless associated with H. pylori infection. Some
suggested risk factors such as diet, and spice consumption, were hypothesized as ulcerogens
(helping cause ulcers) until late in the 20th century, but have been shown to be of relatively
minor importance in the development of peptic ulcers. Similarly, while studies have found
that alcohol consumption increases risk when associated with H. pylori infection, it does not
seem to independently increase risk & even when coupled with H. pylori infection, the
increase is modest in comparison to the primary risk factor.
PATHOPHYSIOLOGY:
Peptic ulcers result from an imbalance between factors that can damage the gastroduodenal
mucosal lining and defense mechanisms that normally limit the injury. Aggressive factors
include gastric juice (including hydrochloric acid, pepsin, and bile salts refluxed from the
duodenum), H pylori, and NSAIDs. Mucosal defenses comprise a mucus bicarbonate layer
secreted by surface mucus cells forming a viscous gel over the gastric mucosa; the integrity of
tight junctions between adjacent epithelial cells; and the process of restitution, whereby any
break in the epithelial lining is rapidly filled by adjacent epithelial and mucosal stromal cells
migrating and flattening to fill the gap. Mucosal defenses depend on an adequate blood supply
and on formation within the gastric mucosa.
In general, duodenal ulcers are the result of hypersecretion of gastric acid related to H pylori
infection (the majority of cases), whereas secretion is normal or low in patients with gastric
ulcers. In duodenal ulcers, chronic H pylori infection confined mainly to the gastric antrum leads
to impaired secretion of somatostatin and consequently increased gastrin release, resulting in
gastric acid hypersecretion. In Zollinger-Ellison syndrome, a gastrin-secreting neuro-endocrine
tumour is the stimulus for high rates of gastric acid secretion.
In gastric ulcers, longstanding H pylori infection throughout the stomach accompanied by severe
inflammation results in gastric mucin degradation, disruption of tight junctions between gastric
epithelial cells, and the induction of gastric epithelial cell death. NSAIDs cause injury directly
(involving trapping hydrogen ions) and indirectly (a systemic effect involving the inhibition of
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cyclo-oxygenases, especially COX-1) and increase bleeding risk through anti-platelet actions.
Chronic gastric ischaemia underlies the stress ulcers of patients in intensive care.
COMPLICATIONS:
Left untreated, peptic ulcers can result in;
a) Internal bleeding: Gastrointestinal bleeding is the most common complication. Sudden
large bleeding can be life-threatening. It occurs when the ulcer erodes one of the blood
vessels, such as the gastroduodenal artery.
b) Perforation: Perforation (a hole in the wall) often leads to catastrophic consequences.
Erosion of the gastro-intestinal wall by the ulcer leads to spillage of stomach or intestinal
content into the abdominal cavity. Perforation at the anterior surface of the stomach leads
to acute peritonitis, initially chemical and later bacterial peritonitis. The first sign is often
sudden intense abdominal pain. Posterior wall perforation leads to bleeding due to
involvement of gastroduodenal artery that lies posterior to the 1st part of duodenum.
c) Penetration: Penetration is when the ulcer continues into adjacent organs such as the liver
and pancreas.
d) Scar tissue: Scarring and swelling due to ulcers causes narrowing in the duodenum and
gastric outlet obstruction. Patient often presents with severe vomiting.
e) Cancer is included in the differential diagnosis (elucidated by biopsy), Helicobacter pylori
as the etiological factor making it 3 to 6 times more likely to develop stomach cancer from
the ulcer.
SIGNS AND SYMPTOMS:
Symptoms of a peptic ulcer can be
 Abdominal pain, classically epigastric with severity relating to mealtimes, after around
three hours of taking a meal (duodenal ulcers are classically relieved by food, while
gastric ulcers are exacerbated by it).
 Bloating and abdominal fullness.
 Waterbrash (rush of saliva after an episode of regurgitation to dilute the acid in
esophagus - although this is more associated with gastroesophageal reflux disease);
 Nausea, and copious vomiting.
 Loss of appetite and weight loss.
 Hematemesis (vomiting of blood); this can occur due to bleeding directly from a gastric
ulcer, or from damage to the esophagus from severe/continuing vomiting.
 Melena (tarry, foul-smelling feces due to oxidized iron from hemoglobin).
 Rarely, an ulcer can lead to a gastric or duodenal perforation, which leads to acute
peritonitis. This is extremely painful and requires immediate surgery.
DIAGNOSIS:
In order to detect an ulcer, you may have to undergo diagnostic tests, such as:
1. Physical examination: The diagnosis is mainly established based on the characteristic
symptoms. Stomach pain is usually the first signal of a peptic ulcer. In some cases, doctors
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may treat ulcers without diagnosing them with specific
tests and observe whether the symptoms resolve, thus
indicating that their primary diagnosis was accurate.
2. Laboratory tests: Confirmation of the diagnosis is made
with the help of tests such as endoscopies or barium
contrast x-rays. The tests are typically ordered if the
symptoms do not resolve after a few weeks of treatment,
or when they first appear in a person who is over age 45 or
who has other symptoms such as weight loss, because
stomach cancer can cause similar symptoms. Also, when
severe ulcers resist treatment, particularly if a person has
several ulcers or the ulcers are in unusual places, a doctor may suspect an underlying
condition that causes the stomach to overproduce acid.
Blood tests are not reliable for accurate peptic ulcer diagnosis on their own is their inability
to differentiate between past exposure to the bacteria and current infection. Additionally, a
false negative result is possible with a blood test if the patient has recently been taking
certain drugs, such as antibiotics or proton pump inhibitors. These tests are;
i. Endoscopy: An esophagogastroduodenoscopy (EGD), a form of endoscopy, also
known as a gastroscopy, is carried out on patients in whom a peptic ulcer is suspected.
By direct visual identification, the location and severity of an ulcer can be described.
Moreover, if no ulcer is present, EGD can often provide an alternative diagnosis.
ii. X-ray of your upper digestive system. Sometimes called a barium swallow or upper
gastrointestinal series, this series of X-rays creates images of your esophagus, stomach
and small intestine. During the X-ray, you swallow a white liquid (containing barium)
that coats your digestive tract and makes an ulcer more visible.
iii. Tests for H. pylori. Your doctor may recommend tests to determine whether the
bacterium H. pylori is present in your body. Which type of test you undergo depends on
your situation. H. pylori may be detected in a blood test, a stool test or a breath test. For
the breath test, you drink a small glass of clear, tasteless liquid that contains radioactive
carbon. H. pylori breaks down the substance in your stomach. Later, you blow into a
bag, which is then sealed. If you're infected with H. pylori, your breath sample will
contain the radioactive carbon in the form of carbon dioxide.
TREATMENT:
Along with reducing stress and modifying lifestyle, doctors treat gastric and duodenal ulcers with
several types of medicines, including H2-blockers, proton-pump inhibitors and mucosal
protective agents. When treating H. pylori, these medications are used in combination with
antibiotics. If medication is ineffective or complications arise, surgery may be required.
Medications: These are;
i. H2-blockers: It reduce the amount of acid that the stomach makes. These medicines
include cimetidine (Tagamet), ranitidine (Zantac), famotidine (Pepcid) and nizatidine
(Axid). A single bedtime dose starts healing a duodenal ulcer in four weeks and a gastric
ulcer in six to eight weeks.
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iii.
iv.
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Proton-pump inhibitors: It modify the stomach's production of acid by stopping the
stomach's acid pump - the final step of acid secretion. The recently approved and now
available drug, omeprazole (Prilosec), is 10 times more powerful in suppressing stomach
acid production than the H2-blockers, able to promote duodenal ulcer healing in two to
four weeks. This potent acid-inhibitor can suppress about 95 percent of stomach acid
production. It is especially useful for treating people whose ulcers fail to respond to H2receptor blockers or other medications and those with Zollinger-Ellison syndrome.
Mucosal protective agents: It protect the stomach's mucous lining from acid. The
prescription medications are sucralfate (Sulcrate or Carafate) and misoprostol (Cytotec).
The non-prescription medications are antacids (such as Tums and Rolaids) and bismuth
subsalicylate (Pepto-Bismol).
Antibiotics: With the discovery of the link between ulcers and H. pylori peptic ulcers can
be treated by a short course of combined high dose antibiotic therapy rather than acidsuppression alone. Without antibacterial therapy, there is a 75 percent chance of the ulcer
reoccurring. With antibacterial therapy, there is a 1 percent chance of the ulcer
reoccurring. There are two types of combination therapies currenly being used: triple
therapy and dual therapy.
Regimens of medications: These are;
a. Dual therapy: It involves;
 Amoxicillin two to four times a day or Biaxin three times a day (or
clarithromycin).
 Prilosec two times a day (anti ulcer drugs)
This regimen lasts two weeks. This treatment is 80 percent effective in destroying the H.
pylori bacteria and in reducing the risk of reoccurrence.
b. Triple therapy: It involves;
 Metronidazole (Flagyl)*, an antibiotic taken four times a day.
 Tetracycline (Achromycin or Sumycin)**, an antibiotic taken four times a day.
 Pepto-Bismol taken four times a day (anti ulcer drugs).
This regimen lasts two weeks. This treatment is 90 percent effective in destroying the H.
pylori bacteria and in reducing the risk of reoccurrence. (*doctor may substitute
amoxicillin (Amoxil or Trimox); doctor may substitute clarithromycin (Biaxin)).
c. Four drug therapy: It involves;
 Proton pump inhibitors or H2 blockers.
 Clarithromycin
 Amoxacillin
 Bismith subsalicylate
Surgery: The most common types of surgery for ulcers are vagotomy, antrectomy and
pyloroplasty. These are;
i. Vagotomy involves cutting the vagus nerve that transmits messages from the brain to the
stomach. This interruption reduces acid secretion.
ii. Antrectomy removes the lower part of the stomach (antrum) which produces a hormone
that stimulates the stomach to secrete digestive juices. This enlarges the opening into the
duodenum and small intestine (pyloris), enabling contents to pass more freely from the
stomach.
iii. Pyloroplasty may be performed with a vagotomy.
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PREVENTION:
You may reduce your risk of peptic ulcer if you:
 Protect yourself from infections: It's not clear just how H. pylori spreads, but there's
some evidence that it could be transmitted from person to person or through food and
water. You can take steps to protect yourself from infections, such as H. pylori, by
frequently washing your hands with soap and water and by eating foods that have been
cooked completely.
 Use caution with pain relievers. If you regularly use pain relievers that increase your
risk of peptic ulcer, take steps to reduce your risk of stomach problems. For instance, take
your medication with meals. Work with your doctor to find the lowest dose possible that
still gives you pain relief. Avoid drinking alcohol when taking your medication, since the
two can combine to increase your risk of stomach upset.
8.
MALARIA
INTRODUCTION:
Malaria is a mosquito-borne infectious disease of humans and other animals caused by protists
(a type of microorganism) of the genus Plasmodium. The
term malaria originates from Medieval Italian: mala
aria "bad air"; the disease was formerly called ague or
marsh fever due to its association with swamps and
marshland. The protists first infect the liver, then act as
parasites within red blood cells, causing symptoms that
typically include fever and headache, in severe cases
progressing to coma or death. The disease is widespread in
tropical and subtropical regions in a broad band around the
equator, including much of Sub-Saharan Africa, Asia, and the
Americas. Five species of Plasmodium can infect and be transmitted by humans. Severe malaria
is largely caused by P. falciparum while the disease caused by P. vivax, P. ovale, and
P. malariae is generally a milder form that is rarely fatal. The zoonotic species P. knowlesi,
prevalent in Southeast Asia, causes malaria in macaques but can also cause severe infections in
humans. Malaria is prevalent in tropical regions because the significant amounts of rainfall,
consistently high temperatures and high humidity, along with stagnant waters in which mosquito
larvae readily mature, provide them with the environment they need for continuous breeding.
HISTORY:
Malaria has infected humans for over 50,000 years, and Plasmodium may have been a human
pathogen for the entire history of the species. Close relatives of the human malaria parasites
remain common in chimpanzees. Some new evidence suggests that the most virulent strain of
human malaria may have originated in gorillas. References to the unique periodic fevers of
malaria are found throughout recorded history, beginning in 2700 BC in China. Malaria may
have contributed to the decline of the Roman Empire, and was so pervasive in Rome that it was
known as the "Roman fever". Several regions in ancient Rome were considered at-risk for the
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disease because of the favorable conditions present for malaria vectors. This included areas such
as southern Italy, the island of Sardinia, the Pontine Marshes, the lower regions of coastal Etruria
and the city of Rome along the Tiber River.
The first effective treatment for malaria came from the bark of cinchona tree, which contains
quinine. This tree grows on the slopes of the Andes, mainly in Peru. The indigenous peoples of
Peru made a tincture of cinchona to control malaria. The Jesuits noted the efficacy of the practice
and introduced the treatment to Europe during the 1640s, where it was rapidly accepted.
Scientific studies on malaria made their first significant advance in 1880, when a French army
doctor working in the military hospital named Charles Louis Alphonse Laveran observed
parasites for the first time, inside the red blood cells of people suffering from malaria. He
therefore proposed that malaria is caused by this organism, the first time a protist was identified
as causing disease. For this and later discoveries, he was awarded the 1907 Nobel Prize for
Physiology or Medicine. In April 1894, a Scottish physician Sir Ronald Ross visited proved that
mosquito was the vector for malaria in humans by showing that certain mosquito species
transmit malaria to birds. He isolated malaria parasites from salivary glands of mosquitoes that
had fed on infected birds. For this work, Ross received 1902 Nobel Prize in Medicine.
EPIDEMIOLOGY:
Based on documented cases, the WHO estimates that there were 216 million cases of malaria in
2010 resulting in 655,000 deaths. Average cases per year are 350-500 millions, in which one
million die. An estimate in The Lancet, based on a systematic analysis of all available mortality
data combined with empirical methods for estimating causes of death, places the number of
deaths in 2010 at 1.24 million. The majority of cases occur in children under five years old;
pregnant women are also especially vulnerable. Malaria is presently endemic in a broad band
around the equator, in areas of the Americas, many parts of Asia, and much of Africa; however,
it is in sub-Saharan Africa where 85–90% of malaria fatalities occur. The geographic distribution
of malaria within large regions is complex, and malaria-afflicted and malaria-free areas are often
found close to each other. Malaria is prevalent in tropical regions because of the significant
amounts of rainfall, consistent high temperatures and high humidity, along with stagnant waters
in which mosquito larvae readily mature, providing them with the environment they need for
continuous breeding. In drier areas, outbreaks of malaria have been predicted with reasonable
accuracy by mapping rainfall. Malaria is more common in rural areas than in cities; this is in
contrast to dengue fever where urban areas present the greater risk. The global endemic levels of
malaria have not been mapped since the 1960s.
ETIOLOGY:
1. Plasmodium: Malaria parasites are from the genus Plasmodium (phylum Apicomplexa).
There are many different types of Plasmodium parasite, but only five types cause malaria in
humans. These are listed below.


Plasmodium falciparum: mainly found in Africa and responsible for most malaria
deaths worldwide.
Plasmodium vivax: mainly found in Asia and Latin America. This parasite produces less
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


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severe symptoms than Plasmodium falciparum, but it can stay in the liver for up to three
years, which can result in relapses.
Plasmodium ovale: fairly uncommon and usually found in West Africa. It can remain in
your liver for several years without producing symptoms.
Plasmodium malariae: this is quite rare and usually only found in Africa.
Plasmodium knowlesi: this is very rare and found in parts of Southeast Asia.
TRANSMISSION:
The transmission modes are;
a) Anopheles mosiquito: Principal mode of spread
of malaria is by the bites of female Anopheles
(Gk., hurtful, harmful) mosquito. Of more than
480 species of Anopheles, only about 50 species
transmit malaria, with every continent having its
own species of these mosquitoes: An. gambiae
complex in Africa, An. freeborni in North
America, An. culicifacies, An. fluviatilis, An.
minimus, An. philippinensis, An. stephensi, and
An. sundaicus in the Indian subcontinent. An.
leucosphyrus, An. latens, An. cracens, An. hackeri, An. dirus etc., have been identified as
the vectors for the transmission of P. knowlesi.
b) Other modes of transmission: Rarely malaria can spread by the inoculation of blood
from an infected person to a healthy person. In this type of malaria, asexual forms are
directly inoculated into the blood and pre-erythrocytic development of the parasite in the
liver does not occur. Therefore, this type of malaria has a shorter incubation period and
relapses due to persisting exoerythrocytic forms do not occur. These are;
i.
Mother to the growing fetus (Congenital malaria): Transfer of parasitized red
cells from infected mother to the child either transplacentally or during labor can
lead to in malaria in the newborn, called as congenital malaria. Congenital
malaria seems to be rarely reported and has always been considered to be more
frequent in the nonimmune population than in the endemic areas.
ii.
Transfusion Malaria: Malaria can be transmitted by transfusion of blood from
infected donors. First reported in 1911, transfusion malaria is one of the most
common transfusion-transmitted infections today.
iii.
Needle stick injury: Cases of malaria transmission through needle-stick injuries,
accidentally among health care professionals (some even fatal) or due to needle
sharing among drug addicts, have also been reported.
iv.
Organ transplant: During this process malaria alsdo transmit.
INCUBATION PERIOD:
In the case of malaria, the incubation period for the disease (the period between infection and the
beginning of symptoms) typically lasts between 10 days to four weeks. In some cases, the
malaria incubation period may be as short as seven days or as long as several years. Factors that
affect the incubation period for malaria include the type of Plasmodium parasite responsible for
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the infection. When antimalarial drugs are used to prevent the spread of the disease, they may
also increase the length of the malaria incubation period by weeks or months. For most people,
the malaria incubation period is between 10 days to four weeks after the bite from the infected
Anopheles mosquito, although a person may feel ill as early as seven days after infection, or as
late as several years later. The malaria incubation period will vary depending on the type of
Plasmodium parasite responsible for the infection.
Plasmodium falciparum tends to have a shorter incubation period, while Plasmodium malariae
tends to have a longer incubation period. The other kinds of malaria, Plasmodium vivax and
Plasmodium ovale, can have a much longer malaria incubation period. For these parasites, a
proportion of them may begin to grow immediately in the liver and cause symptoms after the
normal incubation period. The remaining portion may remain inactive ("dormant") in the liver
for several months (and up to about four years) after a person is bitten by an infected mosquito.
When these parasites come out of hibernation, begin multiplying and then invade red blood cells,
the person will become sick again. These "sleeping" forms are the causes of the relapses seen
with these two species.
PATHOPHYSIOLOGY OF MALARIA:
Malaria infection develops via two phases: one that involves the liver or hepatic system
(exoerythrocytic), and one which involves red blood cells, or erythrocytes (erythrocytic). When
an infected mosquito pierces a person's skin to take a blood meal, sporozoites in the mosquito's
saliva enter the bloodstream and migrate to the liver where they infect hepatocytes, multiplying
asexually and asymptomatically for a period of 8–30 days. After a potential dormant period in
the liver, these organisms differentiate to yield thousands of merozoites, which, following
rupture of their host cells, escape into the blood and infect red blood cells to begin the
erythrocytic stage of the life cycle. The parasite escapes from the liver undetected by wrapping
itself in the cell membrane of the infected host liver cell. Some P. vivax sporozoites do not
immediately develop into exoerythrocytic-phase merozoites, but instead produce hypnozoites
that remain dormant for periods ranging from several months (6–12 months is typical) to as long
as three years. After a period of dormancy, they reactivate and produce merozoites. Hypnozoites
are responsible for long incubation and late relapses in P. vivax infections, although their
existence in P. ovale is uncertain.
The parasite is relatively protected from attack by the body's immune system because for most of
its human life cycle it resides within the liver and blood cells and is relatively invisible to
immune surveillance. However, circulating infected blood cells are destroyed in the spleen. To
avoid this fate, the P. falciparum parasite displays adhesive proteins on the surface of the
infected blood cells, causing the blood cells to stick to the walls of small blood vessels, thereby
sequestering the parasite from passage through the general circulation and the spleen. The
blockage of the microvasculature causes symptoms such as in placental and cerebral malaria. In
cerebral malaria the sequestrated red blood cells can breach the blood brain barrier possibly
leading to coma. Some merozoites turn into male and female gametocytes. If a mosquito pierces
the skin of an infected person, it potentially picks up gametocytes within the blood. Fertilization
and sexual recombination of the parasite occurs in the mosquito's gut. New sporozoites develop
and travel to the mosquito's salivary gland, completing the cycle. Pregnant women are especially
attractive to the mosquitoes, and malaria in pregnant women is an important cause of stillbirths,
infant mortality and low birth weight.
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FIGURE: A mosquito causes infection by taking a blood meal. First, sporozoites enter the bloodstream,
and migrate to the liver. They infect liver cells, where they multiply into merozoites, rupture the liver
cells, and return to the bloodstream. Then, the merozoites infect red blood cells, where they develop into
ring forms, trophozoites and schizonts that in turn produce further merozoites. Sexual forms are also
produced, which, if taken up by a mosquito, will infect the insect and continue the life cycle.
SIGNS AND SYMPTOMS:
The signs and symptoms of malaria typically begin 8–25 days
following infection. However, symptoms may occur later in those
who have taken antimalarial medications as prevention. The
presentation may include fever, shivering, arthralgia (joint pain),
vomiting, hemolytic anemia, jaundice, hemoglobinuria, retinal
damage, and convulsions. Approximately 30% of people however
will no longer have a fever upon presenting to a health care facility.
The classic symptom of malaria is cyclical occurrence of sudden
coldness followed by rigor and then fever and sweating lasting
about two hours or more, occurring every two days in P. vivax and
P. ovale infections, and every three days for P. malariae. P. falciparum
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infection can cause recurrent fever every 36–48 hours or a less pronounced and almost
continuous fever. For reasons that are poorly understood, but that may be related to high
intracranial pressure, children with malaria frequently exhibit abnormal posturing, a sign
indicating severe brain damage. Cerebral malaria is associated with retinal whitening, which may
be a useful clinical sign in distinguishing malaria from other causes of fever.
Severe malaria is usually caused by P. falciparum, and typically arises 6–14 days after infection.
Non-falciparum species have however been found to be the cause of 14% of cases of severe
malaria in some groups. Consequences of severe malaria include coma and death if untreated,
young children and pregnant women are especially vulnerable. Splenomegaly (enlarged spleen),
severe headache, cerebral ischemia, hepatomegaly (enlarged liver), hypoglycemia, and
hemoglobinuria with renal failure may occur. Renal failure is a feature of blackwater fever,
where hemoglobin from lysed red blood cells leaks into the urine.
COMPLICATIONS:
Malaria can be fatal, particularly the variety that's common in tropical parts of Africa. The
Centers for Disease Control and Prevention estimate that 90 percent of all malaria deaths occur
in Africa, most commonly in children under the age of 5. In most cases, malaria deaths are
related to one or more of these serious complications:
i. Cerebral malaria. If parasite-filled blood cells block small blood vessels to your brain
(cerebral malaria), swelling of your brain or brain damage may occur.
ii. Breathing problems. Accumulated fluid in your lungs (pulmonary edema) can make it
difficult to breathe.
iii. Organ failure. Malaria can cause your kidneys or liver to fail, or your spleen to rupture.
Any of these conditions can be life-threatening.
iv.
Severe anemia. Malaria damages red blood cells, which can result in severe anemia.
v. Low blood sugar. Severe forms of malaria itself can cause low blood sugar, as can
quinine, one of the most common medications used to combat malaria. Very low blood
sugar can result in coma or death.
vi.
Recurrence may occur: Some varieties of the malaria parasite, which typically cause
milder forms of the disease, can persist for years and cause relapses.
vii.
Other complications: Other complications that can arise due to severe malaria include;
 Shock (a sudden drop in blood flow)
 Spontaneous bleeding
 Abnormally low blood sugar
 Swelling and rupturing of the spleen
 Dehydration (a lack of water in the body)
DIAGNOSIS:
1. Physical examination: Examin the patient with detail. Check the breath, temperature etc,
which helps in diagnosis of malaria. Areas that cannot afford laboratory diagnostic tests often
use only a history of subjective fever as the indication to treat for malaria.
2. Laboratory tests:
i. Blood tests (Microscopy): Malaria is typically diagnosed by the microscopic
examination of blood using blood films. A drop of the patient’s blood is collected by
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fingerprick, or from a larger venous blood specimen. It is then spread on a glass slide
(blood smear), dipped in a reagent that stains the malaria parasites (Giemsa stain), and
examined under a microscope at a 1000-fold magnification. Malaria parasites are
recognizable by their physical features and by the appearance of the red blood cells that
they have infected..
Blood tests can help tailor treatment by determining:
 Whether you have malaria
 Which type of malaria parasite is causing your symptoms
 If your infection is caused by a parasite resistant to certain drugs
 Whether the disease is affecting any of your vital organs
Some blood tests can take several days to complete, while others can produce results in
less than 15 minutes.
ii. Malaria Rapid Diagnostic Tests: Malaria Rapid Diagnostic Tests (RDTs) assist in the
diagnosis of malaria by detecting evidence of malaria parasites in human. Malaria RDTs,
also known as Dipsticks or Malaria Rapid Diagnostic Devices (MRDDs), have potential
to greatly improve the quality of management of malaria infections in these areas when
the main alternative form of diagnosis, high quality microscopy, is not readily available.
RDTs are an alternative to diagnosis based on clinical grounds or microscopy. Variations
occur between malaria RDT products, though the principles of the tests are similar.
Malaria RDTs detect specific antigens (proteins) produced by malaria parasites, that are
present in the blood of infected or recently infected individuals. Some RDTs can detect
only one species (Plasmodium falciparum), some also detect other species of the parasite
(P. vivax, P. malariae and P. ovale).
iii. Other Laboratory Tests: In addition to microscopy, other methods have been developed
recently for detection of malaria parasites. Parasite antigens and other products can be
detected by rapid “dipstick” tests, and parasite DNA can be detected by polymerase chain
reaction (PCR). PCR is currently the most accurate test and can identify low levels of
infection not detectable by other methods. Serology detects antibodies against malaria
parasites. Such antibodies are produced by the immune response of the infected person
and can persist in the blood for several months after the infection is over. Thus, serology
measures a person’s past experience with malaria, but does not necessarily detect current
infections. Another test is quantitative parasitaemia count also using for malaria. While
microscopy is a routine test, PCR and serology can be performed only in specialized
reference laboratories.
TREATMENT:
The types of drugs and the length of treatment will vary, depending on:
 Which type of malaria parasite you have
 The severity of your symptoms
 Your age
 Whether you're pregnant
Medications:
There are several medications available to treat malaria, including
i. Chloroquine (Aralen Phosphate), 500mg
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ii.
iii.
iv.
v.
vi.
vii.
viii.
ix.
CLINICAL THERAPEUTICS
Atovaquone-proguanil (Malarone),
Artemether-lumefantrine (Coartem),
Mefloquine (Lariam),
Quinine (Qualaquin),
Quinidine (Quinaglute Dura-Tabs, Quinidex Extentabs, Quin-Release),
Doxycycline (Adoxa, Alodox, Avidoxy, Doryx, Monodox, Oracea, Oraxyl, Periostat,
Vibramycin, Vibramycin Calcium, Vibramycin Monohydrate, Vibra-Tabs, used in
combination with quinine),
Clindamycin (Cleocin HCl, Cleocin Pediatric, used in combination with quinine),
Artesunate (available only through the CDC).
The choice of drug depends on the species of Plasmodium and the risk of drug-resistance in the
area where the malaria was acquired. In sub-Saharan Africa, for example, older drugs like
chloroquine are largely ineffective. Most medications are available only in tablet or pill form.
Intravenous treatment with quinidine may be needed in severe malaria or when the patient cannot
take oral medications. Malaria during pregnancy requires treatment by someone who is expert in
this area. Miscarriage and maternal death may occur, even in the best of hands.
Malaria prophylaxis medications: Several drugs, most of which are used for treatment of
malaria, can be taken to prevent contracting the disease during travel to endemic areas.
Chloroquine may be used where the parasite is still sensitive. However, due to resistance one of
three medications namely mefloquine (Lariam), doxycycline (available generically), or the
combination of atovaquone and proguanil hydrochloride (Malarone) is frequently needed.
Doxycycline and the atovaquone and proguanil combination are the best tolerated; mefloquine is
associated with higher rates of neurological and psychiatric symptoms.
Malaria treatment medications: The treatment of malaria depends on the severity of the
disease; whether people can take oral drugs or must be admitted depends on the assessment and
the experience of the clinician.
i.
ii.
Uncomplicated malaria: Uncomplicated malaria may be treated with oral medications.
The most effective strategy for P. falciparum infection is the use of artemisinins in
combination with other antimalarials (known as artemisinin-combination therapy). This is
done to reduce the risk of resistance against artemisinin. These additional antimalarials
include amodiaquine, lumefantrine, mefloquine or sulfadoxine/pyrimethamine. Another
recommended combination is dihydroartemisinin and piperaquine. Recently, malaria with
partial resistance to artemisins has occurred in Southeast Asia.
Severe malaria: Severe malaria requires the parenteral administration of antimalarial
drugs. Until the mid 2000s the most used treatment for severe malaria was quinine, but
artesunate has been shown to be superior to quinine in both children and adults.
Treatment of severe malaria also involves supportive measures. Infection with P. vivax,
P. ovale or P. malariae is usually treated on an outpatient basis (while a person is at
home). Treatment of P. vivax requires both treatment of blood stages (with chloroquine
or ACT) as well as clearance of liver forms with primaquine.
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PREVENTION:
These are the methods used to prevent malaria include medications, mosquito eradication and the
prevention of bites.
i.
ii.
iii.
Awareness of risk: Awerness is the best prevention of malaria, CDC is trying in these
part also.
Counseling with doctor: Malaria is a potentially fatal illness. People planning to travel
to an area with malaria should see their physician before travel, preferably six weeks
before departure. Travelers should use mosquito precautions and take medications to
reduce the risk of disease.
Reducing exposure to mosquitoes: In countries where malaria is common, prevention
also involves keeping mosquitoes away from humans. Strategies include:
a. Spraying your home. Treating your home's walls with insecticide can help kill
adult mosquitoes that come inside.
b. Sleeping under a net. Bed nets, particularly those treated with insecticide, are
especially recommended for pregnant women and young children.
c. Covering your skin. During active mosquito times, usually from dusk to dawn,
wear pants and long-sleeved shirts.
d. Spraying clothing and skin. Sprays containing permethrin are safe to use on
clothing, while sprays containing DEET can be used on skin.
e. Use mosquito repellent cream: Mosquito repellent containing diethyl toluamide
(DEET) is recommended as the most effective form of bite-preventive treatment.
It has an excellent safety profile in adults, children and pregnant women and has
been used in over 8 billion doses in the last 50 years.
iv.
Prophylactic medications: Several medications are available to prevent malaria. The
choice of medication used for prophylaxis depends on the area of the world that is being
visited and the drug-resistance pattern in that area. In general, the medications are started
before travel, taken while in the malarious area, and continued for a period of time after
leaving the area.
9. INFECTIVE MENINGITIS
INTRODUCTION:
Meningitis is inflammation of the protective membranes covering the brain and spinal cord,
known collectively as the meninges. The inflammation may be caused by infection with viruses,
bacteria, or other microorganisms, and less commonly by certain drugs. Meningitis can be lifethreatening because of the inflammation's proximity to the brain and spinal cord; therefore the
condition is classified as a medical emergency.
Meningitis can lead to serious long-term consequences such as deafness, epilepsy, hydrocephalus
and cognitive deficits, especially if not treated quickly. Some forms of meningitis (such as those
associated with meningococci, Haemophilus influenzae type B, pneumococci or mumps virus
infections) may be prevented by immunization.
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HISTORY
Some suggest that Hippocrates may have realized the existence of meningitis. The description of
tuberculous meningitis, then called "dropsy in the brain", is often attributed to physician Sir
Robert Whytt in a posthumous report that appeared in 1768, although the link with tuberculosis
and its pathogen was not made until the next century. The first recorded major outbreak occurred
in Geneva in 1805. Several other epidemics in Europe and the United States were described
shortly afterward, and the first report of an epidemic in Africa appeared in 1840. African
epidemics became much more common in the 20th century, starting with a major epidemic
sweeping Nigeria and Ghana in 1905–1908. The first report of bacterial infection underlying
meningitis was by the Austrian bacteriologist Anton Weichselbaum, who in 1887 described the
meningococcus. In 1944, penicillin was first reported to be effective in meningitis. The
introduction in the late 20th century of Haemophilus vaccines led to a marked fall in cases of
meningitis associated with this pathogen, and in 2002, evidence emerged that treatment with
steroids could improve the prognosis of bacterial meningitis.
EPIDEMIOLOGY
Meningitis is a notifiable disease in many countries, the exact incidence rate is unknown.
Bacterial meningitis occurs in about 3 people per 100,000 annually in Western countries.
Population-wide studies have shown that viral meningitis is more common, at 10.9 per 100,000,
and occurs more often in the summer. In Brazil, the rate of bacterial meningitis is higher, at 45.8
per 100,000 annually. Sub-Saharan Africa has been plagued by large epidemics of
meningococcal meningitis for over a century, leading to it being labeled the "meningitis belt".
Epidemics typically occur in the dry season (December to June), and an epidemic wave can last
two to three years, dying out during the intervening rainy seasons. Attack rates of 100–800 cases
per 100,000 are encountered in this area, which is poorly served by medical care. The largest
epidemic ever recorded in history swept across the entire region in 1996–1997, causing over
250,000 cases and 25,000 deaths.
There are significant differences in the local distribution of causes for bacterial meningitis. For
instance, while N. meningitides groups B and C cause most disease episodes in Europe, group A
is found in Asia and continues to predominate in Africa, where it causes most of the major
epidemics in the meningitis belt, accounting for about 80% to 85% of documented
meningococcal meningitis cases.
ETIOLOGY:
Meningitis is usually caused by infection from viruses or microorganisms. Most cases are due to
infection with viruses, with bacteria, fungi, and parasites being the next most common causes. It
may also result from various non-infectious causes.
1. Infectious cause:
i. Bacterial cause: The types of bacteria that cause bacterial meningitis vary by age group.
In premature babies and newborns up to three months old, common causes are group B
streptococci and those that normally inhabit the digestive tract such as Escherichia coli
(carrying K1 antigen). Listeria monocytogenes may affect the newborn and occurs in
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epidemics. Older children are more commonly affected by Neisseria meningitidis
(meningococcus), Streptococcus pneumoniae and those under five by Haemophilus
influenzae type B. In adults, N. meningitidis and S. pneumoniae together cause 80% of all
cases of bacterial meningitis, with increased risk of L. monocytogenes in those over 50
years old.
ii. Aseptic cause: The term aseptic meningitis refers loosely to all cases of meningitis in
which no bacterial infection can be demonstrated. This is usually due to viruses, but it
may be due to bacterial infection that has already been partially treated, with
disappearance of the bacteria from the meninges, or by infection in a space adjacent to
the meninges (e.g. sinusitis). Endocarditis (infection of the heart valves with spread of
small clusters of bacteria through the bloodstream) may cause aseptic meningitis. Aseptic
meningitis may also result from infection with spirochetes, a type of bacteria that
includes Treponema pallidum (the cause of syphilis) and Borrelia burgdorferi (known for
causing Lyme disease).
iii. Viral cause: Viruses that can cause meningitis include enteroviruses, herpes simplex
virus type 2 (and less commonly type 1), varicella zoster virus (known for causing
chickenpox and shingles), mumps virus, HIV, and LCMV.
iv. Parasitic cause: A parasitic cause is often assumed when there is a predominance of
eosinophils (a type of white blood cell) in the CSF. The most common parasites
implicated are Angiostrongylus cantonensis, Gnathostoma spinigerum, Schistosoma, as
well as the conditions cysticercosis, toxocariasis, baylisascariasis, paragonimiasis, and a
number of rarer infections and noninfective conditions.
2. Non-infectious causes:
Meningitis may occur as the result of several non-infectious causes such as;
i. Spread of cancer to the meninges (malignant or neoplastic meningitis).
ii. Certain drugs (mainly non-steroidal anti-inflammatory drugs, antibiotics and intravenous
immunoglobulins).
iii. It may also be caused by several inflammatory conditions such as sarcoidosis (which is
then called neurosarcoidosis), connective tissue disorders such as systemic lupus
erythematosus, and certain forms of vasculitis (inflammatory conditions of the blood
vessel wall) such as Behçet's disease.
iv.
Epidermoid cysts and dermoid cysts may cause meningitis by releasing irritant matter
into the subarachnoid space.
TRANSMISSION:
The different types of organisms transmissions are;
1. Viral meningitis:The transmission of viral meningitis is through:
i. People with viral infections expel droplets into the air while coughing. The virus enters
the body when another person inhales the droplets.
ii. Viruses also contaminate various objects, which can spread from hand to mouth.
2. Bacterial meningitis: Meningitis outbreaks often occur in late winter and early spring.
People with bacterial infections release the bacteria into the air on droplets of mucus when
they sneeze or cough.The bacteria enters the lungs of others when they inhale the droplets.
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Once you have been exposed to the bacteria that cause meningitis, it may take 2 to 10 days
before symptoms develop.
3. Fungal meningitis: It is not transmitted from person to person. People at risk for fungal
meningitis acquire the infection usually by inhaling fungal spores from the environment.
4. Parasitic meningitis: Naegleria fowleri infects people by entering the body through the
nose. This typically occurs when people go swimming or diving in warm freshwater places,
like lakes and rivers.
PATHOPHYSIOLOGY:
The meninges comprise three membranes that, together with the cerebrospinal fluid, enclose and
protect the brain and spinal cord (the central nervous system). The pia mater is a very delicate
impermeable membrane that firmly adheres to the surface of the brain, following all the minor
contours. The arachnoid mater (so named because of its spider-web-like appearance) is a loosely
fitting sac on top of the pia mater. The subarachnoid space separates the arachnoid and pia mater
membranes, and is filled with cerebrospinal fluid. The outermost membrane, the dura mater, is a
thick durable membrane, which is attached to both the arachnoid membrane and the skull.
In bacterial meningitis, bacteria reach the meninges by one of two main routes, through the
bloodstream or through direct contact between the meninges and either the nasal cavity or the
skin. In most cases, meningitis follows invasion of the bloodstream by organisms that live upon
mucous surfaces such as the nasal cavity. This is often in turn preceded by viral infections, which
break down the normal barrier provided by the mucous surfaces. Once bacteria have entered the
bloodstream, they enter the subarachnoid space in places where the blood brain barrier is
vulnerable such as the choroid plexus. Direct contamination of the cerebrospinal fluid may arise
from indwelling devices, skull fractures, or infections of the nasopharynx or the nasal sinuses
that have formed a tract with the subarachnoid space (see above); occasionally, congenital
defects of the dura mater can be identified.
The large-scale inflammation that occurs in the subarachnoid space during meningitis is not a
direct result of bacterial infection but can rather largely be attributed to the response of the
immune system to the entrance of bacteria into the central nervous system. When components of
the bacterial cell membrane are identified by the immune cells of the brain (astrocytes and
microglia), they respond by releasing large amounts of cytokines, hormone-like mediators that
recruit other immune cells and stimulate other tissues to participate in an immune response. The
blood brain barrier becomes more permeable, leading to "vasogenic" cerebral edema (swelling of
the brain due to fluid leakage from blood vessels). Large numbers of white blood cells enter the
CSF, causing inflammation of the meninges, and leading to "interstitial" edema (swelling due to
fluid between the cells). In addition, the walls of the blood vessels themselves become inflamed
(cerebral vasculitis), which leads to a decreased blood flow and a third type of edema,
"cytotoxic" edema. The three forms of cerebral edema all lead to an increased intracranial
pressure; together with the lowered blood pressure often encountered in acute infection, this
means that it is harder for blood to enter the brain, and brain cells are deprived of oxygen and
undergo apoptosis (automated cell death).
COMPLICATIONS:
People with meningitis may develop additional problems in the early stages of their illness.
These may require specific treatment. These are;
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1. Common complications: The infection may trigger sepsis, a systemic inflammatory
response syndrome of falling blood pressure, fast heart rate, high or abnormally low
temperature and rapid breathing. Very low blood pressure may occur early, especially but
not exclusively in meningococcal illness; this may lead to insufficient blood supply to
other organs. Disseminated intravascular coagulation, the excessive activation of blood
clotting, may cause both the obstruction of blood flow to organs and a paradoxical
increase of bleeding risk. In meningococcal disease, gangrene of limbs can occur. Severe
meningococcal and pneumococcal infections may result in hemorrhaging of the adrenal
glands, leading to Waterhouse-Friderichsen syndrome, which is often lethal.
2. Brain tissue swelling: The brain tissue may swell, with increasing pressure inside the
skull and a risk of swollen brain tissue causing herniation. This may be noticed by a
decreasing level of consciousness, loss of the pupillary light reflex, and abnormal
posturing. Inflammation of the brain tissue may also obstruct the normal flow of CSF
around the brain (hydrocephalus).
3. Seizures: Seizures may occur for various reasons; in children, seizures are common in
the early stages of meningitis (30% of cases) and do not necessarily indicate an
underlying cause. Seizures may result from increased pressure and from areas of
inflammation in the brain tissue. Focal seizures, persistent seizures, late-onset seizures
and those that are difficult to control with medication are indicators of a poorer long-term
outcome.
4. Abnormilities of cranial nerves: The inflammation of the meninges may lead to
abnormalities of the cranial nerves, a group of nerves arising from the brain stem that
supply the head and neck area and control eye movement, facial muscles and hearing,
among other functions.
5. Other complications: Visual symptoms and hearing loss may persist after an episode of
meningitis. Inflammation of the brain (encephalitis) or its blood vessels (cerebral
vasculitis), as well as the formation of blood clots in the veins (cerebral venous
thrombosis), may all lead to weakness, loss of sensation, or abnormal movement or
function of the part of the body supplied by the affected area in the brain.
SIGN AND SYMPTOMS:
In adults, a severe headache is the most common symptom of meningitis, occurring in almost
90% of cases of bacterial meningitis, followed by nuchal rigidity (inability to flex the neck
forward passively due to increased neck muscle tone and stiffness). The classic triad of
diagnostic signs consists of nuchal rigidity, sudden high fever, and altered mental status;
however, all three features are present in only 44–46% of all cases of bacterial meningitis. If
none of the three signs is present, meningitis is extremely unlikely. Other signs commonly
associated with meningitis include photophobia (intolerance to bright light) and phonophobia
(intolerance to loud noises). Small children often do not exhibit the aforementioned symptoms,
and may only be irritable and look unwell. In infants up to 6 months of age, bulging of the
fontanelle (the soft spot on top of a baby's head) may be present. Other features that might
distinguish meningitis from less severe illnesses in young children are leg pain, cold extremities,
and an abnormal skin color.
Meningitis caused by the bacterium Neisseria meningitidis (known as "meningococcal
meningitis") can be differentiated from meningitis with other causes by a rapidly spreading
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petechial rash which may precede other symptoms. The rash consists of numerous small,
irregular purple or red spots ("petechiae") on the trunk, lower extremities, mucous membranes,
conjuctiva, and (occasionally) the palms of the hands or soles of the feet. The rash is typically
non-blanching: the redness does not disappear when pressed with a finger or a glass tumbler.
DIAGNOSIS:
1. Lumbar puncture: A lumbar puncture is done by positioning the patient, usually lying
on the side, applying local anesthetic, and inserting a needle into the dural sac (a sac
around the spinal cord) to collect cerebrospinal fluid (CSF). When this has been
achieved, the "opening pressure" of the CSF is measured using a manometer. The
pressure is normally between 6 and 18 cm water (cmH2O); in bacterial meningitis the
pressure is typically elevated. The CSF sample is examined for presence and types of
white blood cells, red blood cells, protein content and glucose level. Gram staining of the
sample may demonstrate bacteria in bacterial meningitis, but absence of bacteria does not
exclude bacterial meningitis as they are only seen in 60% of cases; this figure is reduced
by a further 20% if antibiotics were administered before the sample was taken, and Gram
staining is also less reliable in particular infections such as listeriosis. Microbiological
culture of the sample is more sensitive (it identifies the organism in 70–85% of cases) but
results can take up to 48 hours to become available.
The concentration of glucose in CSF is normally above 40% of that in blood. In bacterial
meningitis it is typically lower; the CSF glucose level is therefore divided by the blood
glucose (CSF glucose to serum glucose ratio). A ratio ≤0.4 is indicative of bacterial
meningitis;[21] in the newborn, glucose levels in CSF are normally higher, and a ratio
below 0.6 (60%) is therefore considered abnormal.
2. Postmortem: Meningitis can be diagnosed after death has occurred. The findings from a
post mortem are usually a widespread inflammation of the pia mater and arachnoid layers
of the meninges covering the brain and spinal cord. Neutrophil granulocytes tend to have
migrated to the cerebrospinal fluid and the base of the brain, along with cranial nerves
and the spinal cord, may be surrounded with pus as may the meningeal vessels.
3. Other diagnostic tests: These are often also performed, these are;
i.
Blood cultures are usually sent before initiating antibiotic therapy.
ii.
Blood glucose (to compare with CSF glucose).
iii. FBC, renal function tests
iv.
Coagulation profile: especially if disseminated intravascular coagulation is
suspected.
v.
CXR (lung abscess).
vi.
Culture urine, nasal swabs and stool (virology).
vii.
Perform whole blood real-time PCR testing (EDTA sample) for N. meningitidis to
confirm a diagnosis of meningococcal disease.
viii. CT scan is usually reserved for those with specific adverse clinical features or
when an underlying cause such as mastoiditis is suspected.
ix. MRI can be extremely useful for detecting and monitoring the complications of
meningitis.
x. Other possible investigations:
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 Serum cryptococcal antigen, especially if the baseline is known (less
diagnostic than India ink and CSF cryptococcal antigen).
 Serology of blood, urine, and CSF for specific bacterial antigens is
occasionally recommended if there is diagnostic doubt or in patients with
partially treated meningitis.
 Serum test for syphilis if neurosyphilis is suspected.
TREATMENT:
1. Initial treatment:
Meningitis is potentially life-threatening and has a high mortality rate if untreated; delay in
treatment has been associated with a poorer outcome. Thus treatment with wide-spectrum
antibiotics should not be delayed while confirmatory tests are being conducted. If meningococcal
disease is suspected in primary care, guidelines recommend that benzylpenicillin be administered
before transfer to hospital. Intravenous fluids should be administered if hypotension (low blood
pressure) or shock are present. Given that meningitis can cause a number of early severe
complications, regular medical review is recommended to identify these complications early, as
well as admission to an intensive care unit if deemed necessary. Mechanical ventilation may be
needed if the level of consciousness is very low, or if there is evidence of respiratory failure. If
there are signs of raised intracranial pressure, measures to monitor the pressure may be taken;
this would allow the optimization of the cerebral perfusion pressure and various treatments to
decrease the intracranial pressure with medication (e.g. mannitol). Seizures are treated with
anticonvulsants. Hydrocephalus (obstructed flow of CSF) may require insertion of a temporary
or long-term drainage device, such as a cerebral shunt.
2. Bacterial meningitis:
Appropriate antibiotic treatment for the most common types of bacterial meningitis should
reduce the risk of death to less than 15%, although the risk is higher among elderly patients. The
chosen antibiotic should attain adequate levels in the CSF. Achieving this usually depends on the
drug's lipid solubility, its molecular size, its protein-binding capability, and the state of
inflammation at the meninges. The penicillins, certain cephalosporins (ie, third- and fourthgeneration cephalosporins), the carbapenems, fluoroquinolones, and rifampin provide high CSF
levels. The dose of the chosen antimicrobial agent should always be adjusted based on the renal
and hepatic function of the patient. At times, obtaining serum drug concentrations may be
necessary to ensure adequate levels and to avoid toxicity in drugs with a narrow therapeutic
index (eg, vancomycin, aminoglycosides). Once the pathogen has been identified and
antimicrobial susceptibilities determined, the antibiotics may be modified for optimal targeted
treatment. On the basis of age its is discussed, these are;
Neonate to age 1 month: In neonates to age 1 month, the most common microorganisms are
group B or D streptococci, Enterobacteriaceae (eg, E coli), and L monocytogenes. Primary
treatment is a combination of ampicillin (age 0-7 d: 50 mg/kg IV q8h; age 8-30 d: 50-100
mg/kg IV q6h) plus cefotaxime 50 mg/kg IV q6h (up to 12 g/d). Alternative treatment is
ampicillin (age 0-7 d: 50 mg/kg IV q8h; age 8-30 d: 50-100 mg/kg IV q6h) plus gentamicin
(age 0-7 d: 2.5 mg/kg IV or IM q12h; age 8-30 d: 2.5 mg/kg IV or IM q8h). Most authorities
recommend adding acyclovir 10 mg/kg IV q8h for herpes simplex encephalitis.
Age 1-3 months: In infants (1-3 mo), primary treatment is cefotaxime (50 mg/kg IV q6h, up
to 12 g/d) or ceftriaxone (initial dose: 75 mg/kg, 50 mg/kg q12h up to 4 g/day) plus
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ampicillin (50-100 mg/kg IV q6h). Alternative treatment is chloramphenicol (25 mg/kg PO
or IV q12h) plus gentamicin (2.5 mg/kg IV or IM q8h). If prevalence of cephalosporinresistant S pneumoniae (DRSP) is greater than 2%, add vancomycin (15 mg/kg IV q8h).
Strongly consider dexamethasone (0.4 mg/kg IV q12h for 2 d or 0.15 mg/kg IV q6h for 4 d)
starting 15-20 minutes before first dose of antibiotics.
Age 3 months to 7 years: In older infants or young children (3 mo - 7 y), the most common
microorganisms are S pneumoniae, N meningitidis, and H influenzae. Primary treatment is
either cefotaxime (50 mg/kg IV q6h up to 12 g/d) or ceftriaxone (initial dose: 75 mg/kg, then
50 mg/kg q12h up to 4 g/d). If prevalence of DRSP is greater than 2%, add vancomycin (15
mg/kg IV q8h). In countries with low prevalence of DRSP, consider penicillin G (250,000
U/kg/d IM/IV in 3-4 divided doses). Due to DRSP, penicillin G is no longer recommended.
Alternative treatment (or if severely penicillin allergic) is chloramphenicol (25 mg/kg PO/IV
q12h) plus vancomycin (15 mg/kg IV q8h). Strongly consider dexamethasone (0.4 mg/kg IV
q12h for 2 d or 0.15 mg/kg IV q6h for 4 d) starting 15-20 minutes before the first dose of
antibiotics.
Age 7-50 years: In an older child or an otherwise healthy adult (7-50 y), the most common
microorganisms are S pneumoniae, N meningitidis, and L monocytogenes.
In areas where prevalence of DRSP is greater than 2%, primary treatment is either
cefotaxime (pediatric dose: 50 mg/kg IV q6h up to 12 g/d; adult dose: 2 g IV q4h) or
ceftriaxone (pediatric dose: initial dose: 75 mg/kg, then 50 mg/kg q12h up to 4 g/day; adult
dose: 2 g IV q12h) plus vancomycin (pediatric dose: 15 mg/kg IV q8h; adult dose: 750-1000
mg IV q12h or 10-15 mg/kg IV q12h). Some add rifampin (pediatric dose: 20 mg/kg/d IV;
adult dose: 600 mg PO qd). If Listeria species is suspected, add ampicillin (50 mg/kg IV).
Alternative treatment (or if severely penicillin allergic) is chloramphenicol (12.5 mg/kg IV
q6h: not bactericidal) or clindamycin (pediatric dose: 40 mg/kg/day IV in 3-4 doses; adult
dose: 900 mg IV q8h: active in vitro but no clinical data) or meropenem (pediatric dose: 2040 mg/kg IV q8h; adult dose: 1 g IV q8h: active in vitro but few clinical data; avoid
imipenem, as it is proconvulsant).
Age 50 years and older: In adults older than 50 years or adults with disabling disease or
alcoholism, the most common microorganisms are S pneumoniae, coliforms, H influenzae,
Listeria species, Pseudomonas aeruginosa, and N meningitidis.
Primary treatment if the prevalence of DRSP is greater than 2% is either cefotaxime (2 g IV
q4h) or ceftriaxone (2 g IV q12h) plus vancomycin (750-1000 mg IV q12h or 10-15 mg/kg
IV q12h). If CSF Gram stain shows gram-negative bacilli, use ceftazidime (2 g IV q8h). In
areas of low prevalence of DRSP, use cefotaxime (2 g IV q4h) or ceftriaxone (2 g IV q12h)
plus ampicillin (50 mg/kg IV q6h). Other options for treatment include meropenem,
TMP/SMX, and doxycycline. Data are limited on the need for dexamethasone in adults,
although there is support for its use in developed countries when S pneumoniae is the
suspected organism and suspicion for TB or fungal etiologies is low. Administer the first
dose of dexamethasone (0.4 mg/kg q12h IV for 2 d or 0.15 mg/kg q6h for 4 d) 15-20 minutes
before the first dose of antibiotics.
3. Viral meningitis:
Viral meningitis typically requires supportive therapy only; most viruses responsible for causing
meningitis are not amenable to specific treatment. Viral meningitis tends to run a more benign
course than bacterial meningitis. Herpes simplex virus and varicella zoster virus may respond to
treatment with antiviral drugs such as aciclovir, but there are no clinical trials that have
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specifically addressed whether this treatment is effective. Mild cases of viral meningitis can be
treated at home with conservative measures such as fluid, bedrest, and analgesics.
4. Fungal meningitis:
Fungal meningitis, such as cryptococcal meningitis, is treated with long courses of highly dosed
antifungals, such as amphotericin B and flucytosine. Raised intracranial pressure is common in
fungal meningitis, and frequent (ideally daily) lumbar punctures to relieve the pressure are
recommended, or alternatively a lumbar drain.
5. Parasitic meningitis:
The treatment for helminthic (ie, A cantonensis, G spinigerum) eosinophilic meningitis has
largely been supportive in nature. This includes adequate analgesia, therapeutic CSF aspiration,
and the use of anti-inflammatory agents, such as corticosteroids. The use of antihelminthic
therapy may be contraindicated, because clinical deterioration and death may occur following
severe inflammatory reactions to the dying worms.
6. Syphilitic meningitis:
The treatment of choice for neurosyphilis requires the parenteral administration of aqueous
crystalline penicillin G (2-4 million U/d IV q4h) for 10-14 days, often followed with
intramuscular (IM) benzathine penicillin G (2.4 million U). Alternatively, administer procaine
penicillin G (2.4 million U/d IM) plus probenecid (500 mg PO qid) for 14 days, followed by IM
benzathine penicillin G (2.4 million U).
PREVENTION:
1. Behavioral prevention: Bacterial and viral meningitis are contagious. Neither are as
contagious as the common cold or flu. Both can be transmitted through droplets of
respiratory secretions during close contact such as kissing, sneezing or coughing on
someone, but cannot be spread by only breathing the air where a person with meningitis
has been. Viral meningitis is typically caused by Enteroviruses, and is most commonly
spread through fecal contamination. By changing behavior to prevent the causes of
transmission, infection by viruses and bacteria can be prevented.
2. Pharmaceutical prevention: For some causes of meningitis, prophylaxis can be
provided in the long term with vaccine, or in the short term with antibiotics.
i. Vaccines: Routine vaccination against Streptococcus pneumoniae with the
pneumococcal conjugate vaccine (PCV), which is active against seven common
serotypes of this pathogen, significantly reduces the incidence of pneumococcal
meningitis. The pneumococcal polysaccharide vaccine, which covers 23 strains, is
only administered in certain groups (e.g. those who have had a splenectomy); it does
not elicit a significant immune response in all recipients, e.g. small children.
Childhood vaccination with Bacillus Calmette-Guérin has been reported to
significantly reduce the rate of tuberculous meningitis, but its waning effectiveness in
adulthood has prompted a search for a better vaccine.
ii. Antibiotics: Short-term antibiotic prophylaxis is also a method of prevention,
particularly of meningococcal meningitis. In cases of meningococcal meningitis,
prophylactic treatment of close contacts with antibiotics (e.g. rifampicin,
ciprofloxacin or ceftriaxone) can reduce their risk of contracting the condition, but
does not protect against future infections.
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10. CONGESTIVE HEART FAILURE
INTRODUCTION:
Heart failure (HF), often called congestive heart failure (CHF) or congestive cardiac failure
(CCF), is an inability of the heart to provide sufficient pump action to distribute blood flow to
meet the needs of the body. Heart failure can cause a number of symptoms including shortness of
breath, leg swelling, and exercise intolerance. The condition is diagnosed with echocardiography
and blood tests. Treatment commonly consists of lifestyle measures such as smoking cessation,
light exercise including breathing protocols, decreased salt intake and other dietary changes) and
medications. Sometimes it is treated with implanted devices (pacemakers or ventricular assist
devices) and occasionally a heart transplant.
Heart failure is a common, costly, disabling, and potentially deadly condition. In developed
countries, around 2% of adults suffer from heart failure, but in those over the age of 65, this
increases to 6–10%.
EPIDEMIOLOGY
Heart failure is associated with significantly reduced physical and mental health, resulting in a
markedly decreased quality of life. With the exception of heart failure caused by reversible
conditions, the condition usually worsens with time. Although some people survive many years,
progressive disease is associated with an overall annual mortality rate of 10%.
Heart failure is the leading cause of hospitalization in people older than 65. In developed
countries, the mean age of patients with heart failure is 75 years old. In developing countries,
two to three percent of the population suffers from heart failure, but in those 70 to 80 years old, it
occurs in 20-30 percent. Heart failure affects close to 5 million people in the USA and each year
close to 500,000 new cases are diagnosed. What is of more concern is that more than 50% of
patients seek re-admission within 6 months after treatment and the average duration of hospital
stay is 6 days.
In tropical countries, the most common cause of HF is valvular heart disease or some type of
cardiomyopathy. Moreover as underdeveloped countries become more affluent, there has also
been an increase in diabetes, hypertension and obesity which has resulted in heart failure.
In USA, HF is much higher in African Americans, Hispanics, Native Americans and recent
immigrants from the eastern bloc countries like Russia. This high prevalence in these ethnic
populations has been linked to high incidence of diabetes and hypertension. In many new
immigrants to the USA the high prevalence of heart failure has largely been attributed to lack of
preventive health care or substandard treatment.
Men have a higher incidence of heart failure, but the overall prevalence rate is similar in both
sexes, since women survive longer after the onset of heart failure. New information suggests
that elements of heart failure in African Americans and Caucasians may be different.
ETIOLOGY:
Chronic heart failure: The predominance of causes of heart failure are difficult to analyze due
to challenges in diagnosis, differences in populations, and changing prevalence of causes with
age.
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A 19 year study of 13000 healthy adults in the United States (the National Health and Nutrition
Examination Survey (NHANES I) found the following causes ranked by Population Attributable
Risk score:
1. Ischaemic heart disease 62%
2. Cigarette smoking 16%
3. Hypertension (high blood pressure)10%
4. Obesity 8%
5. Diabetes 3%
6. Valvular heart disease 2% (much higher in older populations)
Rarer causes of heart failure include:
 Viral myocarditis (an infection of the heart muscle)
 Infiltrations of the muscle such as amyloidosis
 HIV cardiomyopathy (caused by human immunodeficiency virus)
 Connective tissue diseases such as systemic lupus erythematosus
 Abuse of drugs such as alcohol and cocaine
 Pharmaceutical drugs such as chemotherapeutic agents
 Arrhythmias
Obstructive sleep apnea (a condition of sleep wherein disordered breathing overlaps with
obesity, hypertension, and/or diabetes) is regarded as an independent cause of heart failure.
Acute decompensated heart failure: Chronic stable heart failure may easily decompensate.
This most commonly results from an intercurrent illness (such as pneumonia), myocardial
infarction (a heart attack), arrhythmias, uncontrolled hypertension, or a patient's failure to
maintain a fluid restriction, diet, or medication. Other well recognized precipitating factors
include anemia and hyperthyroidism which place additional strain on the heart muscle. Excessive
fluid or salt intake, and medication that causes fluid retention such as NSAIDs and
thiazolidinediones, may also precipitate decompensation.
PATHOPHYSIOLOGY:
Heart failure is caused by any condition which reduces the efficiency of the myocardium, or
heart muscle, through damage or overloading. As such, it can be caused by as diverse an array of
conditions as myocardial infarction (in which the heart muscle is starved of oxygen and dies),
hypertension (which increases the force of contraction needed to pump blood) and amyloidosis
(in which protein is deposited in the heart muscle, causing it to stiffen). Over time these increases
in workload will produce changes to the heart itself:
a) Reduced force of contraction, due to overloading of the ventricle. In a healthy heart,
increased filling of the ventricle results in increased force of contraction (by the Frank–
Starling law of the heart) and thus a rise in cardiac output. In heart failure this mechanism
fails, as the ventricle is loaded with blood to the point where heart muscle contraction
becomes less efficient. This is due to reduced ability to cross-link actin and myosin
filaments in over-stretched heart muscle.
b) A reduced stroke volume, as a result of a failure of systole, diastole or both. Increased
end systolic volume is usually caused by reduced contractility. Decreased end diastolic
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d)
e)
f)
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volume results from impaired ventricular filling – as occurs when the compliance of the
ventricle falls (i.e. when the walls stiffen).
Reduced spare capacity. As the heart works harder to meet normal metabolic demands,
the amount cardiac output can increase in times of increased oxygen demand (e.g.
exercise) is reduced. This contributes to the exercise intolerance commonly seen in heart
failure. This translates to the loss of one's cardiac reserve. The cardiac reserve refers to
the ability of the heart to work harder during exercise or strenuous activity. Since the
heart has to work harder to meet the normal metabolic demands, it is incapable of
meeting the metabolic demands of the body during exercise.
Increased heart rate, stimulated by increased sympathetic activity in order to maintain
cardiac output. Initially, this helps compensate for heart failure by maintaining blood
pressure and perfusion, but places further strain on the myocardium, increasing coronary
perfusion requirements, which can lead to worsening of ischemic heart disease.
Sympathetic activity may also cause potentially fatal arrhythmias.
Hypertrophy (an increase in physical size) of the myocardium, caused by the terminally
differentiated heart muscle fibres increasing in size in an attempt to improve contractility.
This may contribute to the increased stiffness and decreased ability to relax during
diastole.
Enlargement of the ventricles, contributing to the enlargement and spherical shape of the
failing heart. The increase in ventricular volume also causes a reduction in stroke volume
due to mechanical and contractile inefficiency.[18]
The general effect is one of reduced cardiac output and increased strain on the heart. This
increases the risk of cardiac arrest (specifically due to ventricular dysrhythmias), and reduces
blood supply to the rest of the body. In chronic disease the reduced cardiac output causes a
number of changes in the rest of the body, some of which are physiological compensations, some
of which are part of the disease process:
a) Arterial blood pressure falls. This destimulates baroreceptors in the carotid sinus and
aortic arch which link to the nucleus tractus solitarius. This center in the brain increases
sympathetic activity, releasing catecholamines into the blood stream. Binding to alpha-1
receptors results in systemic arterial vasoconstriction. This helps restore blood pressure
but also increases the total peripheral resistance, increasing the workload of the heart.
Binding to beta-1 receptors in the myocardium increases the heart rate and make
contractions more forceful, in an attempt to increase cardiac output. This also, however,
increases the amount of work the heart has to perform.
b) Increased sympathetic stimulation also causes the hypothalamus to secrete vasopressin
(also known as antidiuretic hormone or ADH), which causes fluid retention at the
kidneys. This increases the blood volume and blood pressure.
c) Reduced perfusion (blood flow) to the kidneys stimulates the release of renin – an
enzyme which catalyses the production of the potent vasopressor angiotensin.
Angiotensin and its metabolites cause further vasocontriction, and stimulate increased
secretion of the steroid aldosterone from the adrenal glands. This promotes salt and fluid
retention at the kidneys, also increasing the blood volume.
d) The chronically high levels of circulating neuroendocrine hormones such as
catecholamines, renin, angiotensin, and aldosterone affects the myocardium directly,
causing structural remodelling of the heart over the long term. Many of these remodelling
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effects seem to be mediated by transforming growth factor beta (TGF-beta), which is a
common downstream target of the signal transduction cascade initiated by
catecholamines[19] and angiotensin II, and also by epidermal growth factor (EGF), which
is a target of the signaling pathway activated by aldosterone[21]
e) Reduced perfusion of skeletal muscle causes atrophy of the muscle fibres. This can result
in weakness, increased fatigueability and decreased peak strength - all contributing to
exercise intolerance.
The increased peripheral resistance and greater blood volume place further strain on the heart
and accelerates the process of damage to the myocardium. Vasoconstriction and fluid retention
produce an increased hydrostatic pressure in the capillaries. This shifts the balance of forces in
favour of interstitial fluid formation as the increased pressure forces additional fluid out of the
blood, into the tissue. This results in edema (fluid build-up) in the tissues. In right-sided heart
failure this commonly starts in the ankles where venous pressure is high due to the effects of
gravity (although if the patient is bed-ridden, fluid accumulation may begin in the sacral region.)
It may also occur in the abdominal cavity, where the fluid build-up is called ascites. In left-sided
heart failure edema can occur in the lungs - this is called cardiogenic pulmonary edema. This
reduces spare capacity for ventilation, causes stiffening of the lungs and reduces the efficiency of
gas exchange by increasing the distance between the air and the blood. The consequences of this
are dyspnea (shortness of breath), orthopnea and paroxysmal nocturnal dyspnea.
Systolic dysfunction: Heart failure caused by systolic dysfunction is more readily recognized. It
can be simplistically described as failure of the pump function of the heart. It is characterized by
a decreased ejection fraction (less than 45%). The strength of ventricular contraction is
attenuated and inadequate for creating an adequate stroke volume, resulting in inadequate cardiac
output. In general, this is caused by dysfunction or destruction of cardiac myocytes or their
molecular components. In congenital diseases such as Duchenne muscular dystrophy, the
molecular structure of individual myocytes is affected. Myocytes and their components can be
damaged by inflammation (such as in myocarditis) or by infiltration (such as in amyloidosis).
Toxins and pharmacological agents (such as ethanol, cocaine, doxorubicin, and amphetamines)
cause intracellular damage and oxidative stress. The most common mechanism of damage is
ischemia causing infarction and scar formation. After myocardial infarction, dead myocytes are
replaced by scar tissue, deleteriously affecting the function of the myocardium. On
echocardiogram, this is manifest by abnormal or absent wall motion.
Because the ventricle is inadequately emptied, ventricular end-diastolic pressure and volumes
increase. This is transmitted to the atrium. On the left side of the heart, the increased pressure is
transmitted to the pulmonary vasculature, and the resultant hydrostatic pressure favors
extravassation of fluid into the lung parenchyma, causing pulmonary edema. On the right side of
the heart, the increased pressure is transmitted to the systemic venous circulation and systemic
capillary beds, favoring extravassation of fluid into the tissues of target organs and extremities,
resulting in dependent peripheral edema.
Diastolic dysfunction: Heart failure caused by diastolic dysfunction is generally described as the
failure of the ventricle to adequately relax and typically denotes a stiffer ventricular wall. This
causes inadequate filling of the ventricle, and therefore results in an inadequate stroke volume.
The failure of ventricular relaxation also results in elevated end-diastolic pressures, and the end
result is identical to the case of systolic dysfunction (pulmonary edema in left heart failure,
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peripheral edema in right heart failure.). Diastolic dysfunction can be caused by processes
similar to those that cause systolic dysfunction, particularly causes that affect cardiac
remodeling.
Diastolic dysfunction may not manifest itself except in physiologic extremes if systolic function
is preserved. The patient may be completely asymptomatic at rest. However, they are exquisitely
sensitive to increases in heart rate, and sudden bouts of tachycardia (which can be caused simply
by physiological responses to exertion, fever, or dehydration, or by pathological
tachyarrhythmias such as atrial fibrillation with rapid ventricular response) may result in flash
pulmonary edema. Adequate rate control (usually with a pharmacological agent that slows down
AV conduction such as a calcium channel blocker or a beta-blocker) is therefore key to
preventing decompensation.
Left ventricular diastolic function can be determined through echocardiography by measurement
of various parameters such as the E/A ratio (early-to-atrial left ventricular filling ratio), the E
(early left ventricular filling) deceleration time, and the isovolumic relaxation time.
COMPLICATIONS:
For people over age 65, heart failure is the number one cause of death, with nearly 290,000
people dying from this disease each year. Nevertheless, although heart failure produces very high
mortality rates, treatment advances in hypertension, heart surgeries, and heart pacemakers are
improving survival rates.
1. Cardiac Cachexia: If patients with heart failure are overweight to begin with, their
condition tends to be more severe. Once heart failure develops, however, an important
indicator of a worsening condition is the occurrence of cardiac cachexia, which is
unintentional rapid weight loss (a loss of at least 7.5% of normal weight within 6
months).
2. Impaired Kidney Function: Heart failure weakens the heart's ability to pump blood.
This can affect other parts of the body including the kidneys (which in turn can lead to
fluid build-up). Decreased kidney function is common in patients with heart failure, both
as a complication of heart failure and as a complication of other diseases associated with
heart failure (such as diabetes). Studies suggest that in patients with heart failure,
impaired kidney function increases the risks for heart complications including
hospitalization and death.
3. Congestion (Fluid Buildup): In left-sided heart failure, fluid builds up first in the lungs.
Later, as right-sided heart failure develops, fluid builds up in the legs, feet, and abdomen.
Fluid buildup is treated with lifestyle measures, such as reducing salt in the diet, as well
as drugs, such as diuretics.
4. Arrhythmias (Irregular Beatings of the Heart): Atrial fibrillation is a rapid quivering
beat in the upper chambers of the heart. It is a major cause of stroke and very dangerous
in people with heart failure. Left bundle-branch block is an abnormality in electrical
conduction in the heart. It develops in about 30% of patients with heart failure.
Ventricular tachycardia and ventricular fibrillation are serious arryhthmias that can occur
in patients when heart function is significantly impaired.
5. Depression: The presence of depression indicates a poorer outlook for the heart. Studies
indicate that depression may have adverse biologic effects on the immune and nervous
systems, blood clotting, blood pressure, blood vessels, and heart rhythms. People who are
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depressed may fail to follow medical instructions and may not take good care of
themselves.
6. Angina and Heart Attacks: While coronary artery disease is a major cause of heart
failure, patients with heart failure are at continued risk for angina and heart attacks.
Special care should be taken with sudden and strenuous exertion, particularly snowshoveling, during colder months.
SIGNS AND SYMPTOMS:
Signs:
a. Left-sided failure: Common respiratory signs are tachypnea (increased rate of breathing)
and increased work of breathing (non-specific signs of respiratory distress). Rales or
crackles, heard initially in the lung bases, and when severe, throughout the lung fields
suggest the development of pulmonary edema (fluid in the alveoli). Cyanosis which
suggests severe hypoxemia, is a late sign of extremely severe pulmonary edema.
Additional signs indicating left ventricular failure include a laterally displaced apex beat
(which occurs if the heart is enlarged) and a gallop rhythm (additional heart sounds) may
be heard as a marker of increased blood flow, or increased intra-cardiac pressure. Heart
murmurs may indicate the presence of valvular heart disease, either as a cause (e.g. aortic
stenosis) or as a result (e.g., mitral regurgitation) of the heart failure.
b. Right-sided failure: Physical examination may reveal pitting peripheral edema, ascites,
and hepatomegaly. Jugular venous pressure is frequently assessed as a marker of fluid
status, which can be accentuated by eliciting hepatojugular reflux. If the right ventricular
pressure is increased, a parasternal heave may be present, signifying the compensatory
increase in contraction strength.
c. Biventricular failure: Dullness of the lung fields to finger percussion and reduced breath
sounds at the bases of the lung may suggest the development of a pleural effusion (fluid
collection in between the lung and the chest wall). Though it can occur in isolated left- or
right-sided heart failure, it is more common in biventricular failure because pleural veins
drain both into the systemic and pulmonary venous system. When unilateral, effusions
are often right sided.
Symptoms:
Heart failure symptoms are traditionally and somewhat arbitrarily divided into "left" and "right"
sided, recognizing that the left and right ventricles of the heart supply different portions of the
circulation. However, heart failure is not exclusively backward failure (in the part of the
circulation which drains to the ventricle).
There are several other exceptions to a simple left-right division of heart failure symptoms. Left
sided forward failure overlaps with right sided backward failure. Additionally, the most common
cause of right-sided heart failure is left-sided heart failure. The result is that patients commonly
present with both sets of signs and symptoms.
a. Left-sided failure: Backward failure of the left ventricle causes congestion of the
pulmonary vasculature, and so the symptoms are predominantly respiratory in nature.
Backward failure can be subdivided into failure of the left atrium, the left ventricle or
both within the left circuit. The patient will have dyspnea (shortness of breath) on
exertion (dyspnée d'effort) and in severe cases, dyspnea at rest. Increasing breathlessness
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on lying flat, called orthopnea, occurs. It is often measured in the number of pillows
required to lie comfortably, and in severe cases, the patient may resort to sleeping while
sitting up. Another symptom of heart failure is paroxysmal nocturnal dyspnea a sudden
nighttime attack of severe breathlessness, usually several hours after going to sleep. Easy
fatigueability and exercise intolerance are also common complaints related to respiratory
compromise.Compromise of left ventricular forward function may result in symptoms of
poor systemic circulation such as dizziness, confusion and cool extremities at rest.
b. Right-sided failure: Backward failure of the right ventricle leads to congestion of
systemic capillaries. This generates excess fluid accumulation in the body. This causes
swelling under the skin (termed peripheral edema or anasarca) and usually affects the
dependent parts of the body first (causing foot and ankle swelling in people who are
standing up, and sacral edema in people who are predominantly lying down). Nocturia
(frequent nighttime urination) may occur when fluid from the legs is returned to the
bloodstream while lying down at night. In progressively severe cases, ascites (fluid
accumulation in the abdominal cavity causing swelling) and hepatomegaly (enlargement
of the liver) may develop. Significant liver congestion may result in impaired liver
function, and jaundice and even coagulopathy (problems of decreased blood clotting)
may occur.
DIAGNOSIS:
No system of diagnostic criteria has been agreed as the gold standard for heart failure.
Commonly used systems are;
1. Imaging: Echocardiography is commonly used to support a clinical diagnosis of heart
failure. This modality uses ultrasound to determine the stroke volume (SV, the amount of
blood in the heart that exits the ventricles with each beat), the end-diastolic volume
(EDV, the total amount of blood at the end of diastole), and the SV in proportion to the
EDV, a value known as the ejection fraction (EF). In pediatrics, the shortening fraction is
the preferred measure of systolic function. Echocardiography can also identify valvular
heart disease and assess the state of the pericardium (the connective tissue sac
surrounding the heart). Echocardiography may also aid in deciding what treatments will
help the patient, such as medication, insertion of an implantable cardioverter-defibrillator
or cardiac resynchronization therapy. Echocardiography can also help determine if acute
myocardial ischemia is the precipitating cause, and may manifest as regional wall motion
abnormalities on echo.
Chest X-rays are frequently used to aid in the diagnosis of CHF. In the compensated
patient, this may show cardiomegaly (visible enlargement of the heart), quantified as the
cardiothoracic ratio (proportion of the heart size to the chest). In left ventricular failure,
there may be evidence of vascular redistribution ("upper lobe blood diversion" or
"cephalization"), Kerley lines, cuffing of the areas around the bronchi, and interstitial
edema.
2. Electrophysiology: An electrocardiogram (ECG/EKG) may be used to identify
arrhythmias, ischemic heart disease, right and left ventricular hypertrophy, and presence
of conduction delay or abnormalities (e.g. left bundle branch block). Although these
findings are not specific to the diagnosis of heart failure a normal ECG virtually excludes
left ventricular systolic dysfunction.
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3. Blood tests: Blood tests routinely performed include electrolytes (sodium, potassium),
measures of renal function, liver function tests, thyroid function tests, a complete blood
count, and often C-reactive protein if infection is suspected. An elevated B-type
natriuretic peptide (BNP) is a specific test indicative of heart failure. Additionally, BNP
can be used to differentiate between causes of dyspnea due to heart failure from other
causes of dyspnea. If myocardial infarction is suspected, various cardiac markers may be
used. According to a meta-analysis comparing BNP and N-terminal pro-BNP
(NTproBNP) in the diagnosis of heart failure, BNP is a better indicator for heart failure
and left ventricular systolic dysfunction. In groups of symptomatic patients, a diagnostic
odds ratio of 27 for BNP compares with a sensitivity of 85% and specificity of 84% in
detecting heart failure.
4. Angiography: Heart failure may be the result of coronary artery disease, and its
prognosis depends in part on the ability of the coronary arteries to supply blood to the
myocardium (heart muscle). As a result, coronary catheterization may be used to identify
possibilities for revascularisation through percutaneous coronary intervention or bypass
surgery.
5. Magnetic resonance imaging (MRI). An MRI uses magnetic fields and radio waves to
create detailed images of your heart.
6. Myocardial biopsy. In this test, your doctor inserts a small flexible biopsy cord into a
vein in your neck or groin, and small pieces of the heart muscle are taken. This test is
performed to diagnose certain types of heart muscle diseases that cause heart failure.
7. Right heart catheterization. In this test, your doctor inserts a thin, flexible tube
(catheter) into a blood vessel (vein) in your neck or groin and guides the catheter to the
heart to measure pressures within the heart chambers. This helps guide treatment in heart
failure.
8. Stress tests. In a stress test or exercise test, you exercise on a treadmill or stationary
bicycle, or take a drug to simulate heart activity during exercise, while an
electrocardiogram (ECG) monitors your heart. The exercise test helps your doctor judge
your therapy's effectiveness and plan the timing of more advanced treatments. Different
types of stress tests measure the heart's response to exercise in different ways and are
used in different situations. Mayo Clinic is one of the few centers in the world that
measures the relaxation response of the heart to exercise, a test used to diagnose diastolic
heart failure.
9. Radionuclide ventriculography or Multiple-gated Acquisition Scanning (MUGA). In
this nuclear medicine test, the doctor injects a small amount of radioactive dye into your
vein and special cameras show how much blood your heart can pump with each beat.
Results of these tests help doctors determine the cause of your symptoms and develop a
treatment plan.
MANAGEMENT:
Treatment focuses on improving the symptoms and preventing the progression of the disease.
Reversible causes of the heart failure also need to be addressed: (e.g. infection, alcohol ingestion,
anemia, thyrotoxicosis, arrhythmia, hypertension). Treatments include lifestyle and
pharmacological modalities.
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Medications:
Doctors usually treat people who have congestive heart failure with medications proven to
relieve symptoms and increase survival in people who have heart failure. Several types of drugs
may help treat your heart failure if you have reduced blood flow pumping out of your heart's
main pumping chamber (left ventricle).
 Angiotensin-converting enzyme (ACE) inhibitors: ACE inhibitors lower blood
pressure, improve blood flow and decrease your heart's workload.
 Angiotensin II (A-II) receptor blockers: These drugs provide several benefits of ACE
inhibitors without the potential side effect of a persistent cough.
 Beta blockers: Beta blockers slow the heart rate, lower blood pressure and lessen the risk
of some abnormal heart rhythms.
 Digoxin: Also known as digitalis, digoxin increases the strength of heart contractions and
tends to slow your heartbeat.
 Diuretics; Diuretics prevent fluid from collecting in your body and decrease fluid in your
lungs, making breathing easier.
 Nesiritide: Nesiritide, is given through a vein (intravenously), is a synthetic version of Btype natriuretic peptide (BNP), a hormone that occurs naturally in your body.
 Aldosterone antagonists: These medications may help heart work better, reverse
scarring of the heart & help prolong your life if you have severe congestive heart failure.
 Inotropes: These are intravenous medications used in severe heart failure patients to
improve heart pumping function and maintain blood pressure.
Sometimes congestive heart failure becomes severe enough to require hospitalization and
monitoring for a few days. While you're in the hospital, you may take medications that quickly
help your heart pump better and relieve your symptoms. You may also receive supplemental
oxygen. People who have severe congestive heart failure that doesn't improve with treatment
may need supplemental oxygen on a long-term basis.
Surgery:
a. Heart valve repair or replacement. Cardiologists may recommend heart valve repair or
replacement surgery to treat an underlying condition that led to congestive heart failure.
Heart valve surgery may relieve your symptoms and improve your quality of life.
b. Coronary bypass surgery. Cardiologists may recommend coronary bypass surgery to
treat your congestive heart failure if your disease results from severely narrowed
coronary arteries.
c. Heart transplant. Some people who have severe congestive heart failure may need a
heart transplant.
d. Myectomy. In a myectomy, the surgeon removes part of the overgrown septal muscle in
your heart to decrease the blockage that occurs in hypertrophic cardiomyopathy.
Surgeons may perform myectomy when medication no longer relieves your symptoms.
Medical devices:
a. Ventricular assist device (VAD). When your weakened heart needs help pumping
blood, surgeons may implant a VAD into your abdomen and attach it to your heart. These
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mechanical heart pumps can be used either as a "bridge" to heart transplant or as
permanent therapy for people who aren't candidates for a transplant. Mayo Clinic offers
VADs to many people who may have no other options.
b. Cardiac resynchronization therapy (CRT) device (biventricular cardiac
pacemaker). A cardiac resynchronization therapy device (biventricular cardiac heart
pacemaker) sends specifically timed electrical impulses to your heart's lower chambers.
CRTs are suitable for people who have moderate to severe congestive heart failure and
abnormal electrical conduction in the heart.
c. Internal cardiac defibrillator (ICD). Doctors implant ICDs under the skin to monitor
and treat fast or abnormal heart rhythms (arrhythmias), which occur in some people who
have heart failure. The ICD sends electrical signals to your heart if it detects a high or
abnormal rhythm to shock your heart into beating more slowly and pumping more
effectively.
Lifestyle changes:
Lifestyle changes often can relieve symptoms of congestive heart failure and prevent your
disease from worsening. Some changes you can make include:
i. Avoiding or limiting alcohol to one drink two or three times a week.
ii. Avoiding or limiting caffeine.
iii. Eating a low-fat, low-sodium diet.
iv.
Exercising by yourself or in a structured cardiac rehabilitation program.
v. Maintaining a healthy weight or losing weight if you're overweight.
11. GOUT
INTRODUCTION:
Gout is a medical condition usually characterized by recurrent attacks of acute inflammatory
arthritis, a red, tender, hot, swollen joint. The metatarsal-phalangeal joint at the base of the big
toe is the most commonly affected (approximately 50% of cases). However, it may also present
as tophi, kidney stones, or urate nephropathy. It is caused by elevated levels of uric acid in the
blood which crystallize, and the crystals are deposited in joints, tendons, and surrounding tissues.
Gout has increased in frequency in recent decades, affecting about 1-2% of the Western
population at some point in their lives. The increase is believed to be due to increasing risk
factors in the population, such as metabolic syndrome, longer life expectancy and changes in
diet. Gout was historically known as "the disease of kings" or "rich man's disease".
HISTORY:
The word "gout" was initially used by Randolphus of Bocking, around 1200 AD. It is derived
from the Latin word gutta, meaning "a drop" (of liquid). Gout has, however, been known since
antiquity. Historically, it has been referred to as "the king of diseases and the disease of kings" or
"rich man's disease". The first documentation of the disease is from Egypt in 2,600 BC in a
description of arthritis of the big toe. The Greek physician Hippocrates around 400 BC
commented on it in his Aphorisms, noting its absence in eunuchs and premenopausal women.
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In 1683, Thomas Sydenham, an English physician, described its occurrence in the early hours of
the morning, and its predilection for older males.
The Dutch scientist Antonie van Leeuwenhoek first described the microscopic appearance of
urate crystals in 1679. In 1848, English physician Alfred Baring Garrod realized this excess uric
acid in the blood was the cause of gout.
EPIDEMIOLOGY:
Gout affects around 1–2% of the Western population at some point in their lifetimes, and is
becoming more common. Rates of gout have approximately doubled between 1990 and 2010.
This rise is believed to be due to increasing life expectancy, changes in diet, and an increase in
diseases associated with gout, such as metabolic syndrome and high blood pressure. A number of
factors have been found to influence rates of gout, including age, race, and the season of the
year. In men over the age of 30 and women over the age of 50, prevalence is 2%. In the United
States, gout is twice as likely in African American males as it is in European Americans. Rates
are high among the peoples of the Pacific Islands and the Māori of New Zealand, but rare in
Australian aborigines, despite a higher mean concentration of serum uric acid in the latter group.
It has become common in China, Polynesia, and urban sub-Saharan Africa. Some studies have
found attacks of gout occur more frequently in the spring. This has been attributed to seasonal
changes in diet, alcohol consumption, physical activity, and temperature.
ETIOLOGY:
Hyperuricemia is the underlying cause of gout. This can occur for a number of reasons, including
diet, genetic predisposition, or underexcretion of urate, the salts of uric acid. Renal
underexcretion of uric acid is the primary cause of hyperuricemia in about 90% of cases, while
overproduction is the cause in less than 10%. About 10% of people with hyperuricemia develop
gout at some point in their lifetimes. The risk, however, varies depending on the degree of
hyperuricemia. When levels are between 415 and 530 μmol/l (7 and 8.9 mg/dl), the risk is 0.5%
per year, while in those with a level greater than 535 μmol/l (9 mg/dL), the risk is 4.5% per year.
1. Lifestyle: Dietary causes account for about 12% of gout and include a strong association
with the consumption of alcohol, fructose-sweetened drinks, meat, and seafood. Other
triggers include physical trauma and surgery. Recent studies have found dietary factors once
believed to be associated are, in fact, not, including the intake of purine-rich vegetables (e.g.,
beans, peas, lentils, and spinach) and total protein. The consumption of coffee, vitamin C and
dairy products, as well as physical fitness, appear to decrease the risk. This is believed to be
partly due to their effect in reducing insulin resistance.
2. Genetics: The occurrence of gout is partly genetic, contributing to about 60% of variability
in uric acid level. Two genes called SLC2A9 and ABCG2 have been found to commonly be
associated with gout, and variations in them can approximately double the risk. A few rare
genetic disorders, including familial juvenile hyperuricemic nephropathy, medullary cystic
kidney disease, phosphoribosylpyrophosphate synthetase superactivity, and hypoxanthineguanine phosphoribosyltransferase deficiency as seen in Lesch-Nyhan syndrome, are
complicated by gout.
3. Medical problems: Gout frequently occurs in combination with other medical problems.
Metabolic syndrome, a combination of abdominal obesity, hypertension, insulin resistance
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and abnormal lipid levels, occurs in nearly 75% of cases. Other conditions commonly
complicated by gout include: polycythemia, lead poisoning, renal failure, hemolytic anemia,
psoriasis, and solid organ transplants. A body mass index greater than or equal to 35
increases a male's risk of gout threefold. Chronic lead exposure and lead-contaminated
alcohol are risk factors for gout due to the harmful effect of lead on kidney function. LeschNyhan syndrome is often associated with gouty arthritis.
4. Medication: Diuretics have been associated with attacks of gout. However, a low dose of
hydrochlorothiazide does not seem to increase the risk. Other medicines that have been
associated include niacin and aspirin (acetylsalicylic acid). The immunosuppressive drugs
ciclosporin and tacrolimus are also associated with gout, the former particularly when used in
combination with hydrochlorothiazide.
5. Age and sex: Gout occurs more often in men than it does in women, primarily because
women tend to have lower uric acid levels than men do. After menopause, however, women's
uric acid levels approach those of men. Men also are more likely to develop gout earlier
usually between the ages of 40 and 50 whereas women generally develop signs and
symptoms after menopause.
PATHOPHYSIOLOGY:
Gout is a disorder of purine metabolism and occurs when its final metabolite, uric acid,
crystallizes in the form of monosodium urate, precipitating in joints, on tendons, and in the
surrounding tissues. These crystals then trigger a local immune-mediated inflammatory reaction,
with one of the key proteins in the inflammatory cascade being interleukin 1β. An evolutionary
loss of uricase, which breaks down uric acid, in humans and higher primates has made this
condition common.
The triggers for precipitation of uric acid are not well understood. While it may crystallize at
normal levels, it is more likely to do so as levels increase. Other factors believed to be important
in triggering an acute episode of arthritis include cool temperatures, rapid changes in uric acid
levels, acidosis, articular hydration, and extracellular matrix proteins, such as proteoglycans,
collagens, and chondroitin sulfate. The increased precipitation at low temperatures partly
explains why the joints in the feet are most commonly affected. Rapid changes in uric acid may
occur due to a number of factors, including trauma, surgery, chemotherapy, diuretics, and
stopping or starting allopurinol. Calcium channel blockers and losartan are associated with a
lower risk of gout as compared to other medications for hypertension.
COMPLICATIONS:
People with gout can develop more-severe conditions, such as:
1. Recurrent gout: Some people may never experience gout signs and symptoms again.
But others may experience gout several times each year. Medications may help prevent
gout attacks in people with recurrent gout.
2. Advanced gout (Tophi): Untreated gout may cause deposits of urate crystals to form
under the skin in nodules called tophi (TOE-fi). Tophi can develop in several areas such
as your fingers, hands, feet, elbows or Achilles tendons along the back of your ankle.
Tophi usually aren't painful, but they can become swollen and tender during gout attacks.
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3. Kidney stones: Urate crystals may collect in the urinary tract of people with gout,
causing kidney stones. Medications can help reduce the risk of kidney stones.
4. Psychological effects: As well as affecting you physically, gout can also affect your
mood, work and home life. The severe pain that gout causes can make it difficult to get
around, which can sometimes lead to feelings of depression or anxiety.
5. Joint damage: Continuing deposition of urate crystals, especially as the hard lumps
(tophi) and damage they cause may eventually damage your joints permanently. If you
don't treat gout by reducing uric acid levels to below saturation point, future attacks may
become more frequent and prolonged, and your likelihood of developing permanent joint
damage will be increased. In the most serious cases surgery may be required to repair or
replace a damaged joint.
SIGNS AND SYMPTOMS:
The signs and symptoms of gout are almost always acute, occurring suddenly, often at night and
without warning. These includes:
1. Intense joint pain: Gout usually affects the large joint of your big toe, but it can occur in
your feet, ankles, knees, hands and wrists. The pain is likely to be most severe within the
first 12 to 24 hours after it begins.
2. Lingering discomfort: After the most severe pain subsides, some joint discomfort may
last from a few days to a few weeks. Later attacks are likely to last longer and affect more
joints.
3. Inflammation and redness: The affected joint or joints become swollen, tender and red.
4. High level of uric acid ib blood: Sustained high levels of uric acid in the blood is a
common gout symptom .
5. Crystals in joints: Presence of uric acid crystals in joint fluid.
6. Deposition of crystals: Deposits of uric acid crystals around joints and other areas such
as the ears.
7. Moving difficulties: Moving the affected limb/s becomes painful.
8. Kidney problems: Chronic gout can lead to decreased kidney function and kidney
stones.
9. Fever: Fever or chills developing.
10. Fast subsidence: A fast subsidence. Gout attacks normally subside within hours or days.
DIAGNOSIS:
Gout may be diagnosed and treated without further investigations in someone with
hyperuricemia and the classic podagra. Synovial fluid analysis should be done, however, if the
diagnosis is in doubt. X-rays, while useful for identifying chronic gout, have little utility in acute
attacks. Tests to help diagnose gout may include:
1. Synovial fluid: A definitive diagnosis of gout is based upon the identification of
monosodium urate crystals in synovial fluid or a tophus. All synovial fluid samples
obtained from undiagnosed inflamed joints should be examined for these crystals. Under
polarized light microscopy, they have a needle-like morphology and strong negative
birefringence. This test is difficult to perform, and often requires a trained observer.[23]
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The fluid must also be examined relatively quickly after aspiration, as temperature and
pH affect their solubility.
2. Blood tests: Hyperuricemia is a classic feature of gout, but it occurs nearly half of the
time without hyperuricemia and most people with raised uric acid levels never develop
gout. Thus, the diagnostic utility of measuring uric acid level is limited. Hyperuricemia is
defined as a plasma urate level greater than 420 μmol/l (7.0 mg/dl) in males and 360
μmol/l (6.0 mg/dl) in females. Other blood tests commonly performed are white blood
cell count, electrolytes, renal function, and erythrocyte sedimentation rate (ESR).
However, both the white blood cells and ESR may be elevated due to gout in the absence
of infection. A white blood cell count as high as 40.0×109/l (40,000/mm3) has been
documented.
3. Differential diagnosis: The most important differential diagnosis in gout is septic
arthritis. This should be considered in those with signs of infection or those who do not
improve with treatment. To help with diagnosis, a synovial fluid Gram stain and culture
may be performed. Other conditions which present similarly include pseudo gout and
rheumatoid arthritis. Gouty tophi, in particular when not located in a joint, can be
mistaken for basal cell carcinoma or other neoplasms.
TREATMENT:
The initial aim of treatment is to settle the symptoms of an acute attack. Repeated attacks can be
prevented by different drugs used to reduce the serum uric acid levels. Options for acute
treatment include nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine and steroids, while
options for prevention include allopurinol, febuxostat and probenecid. Lowering uric acid levels
can cure the disease. Treatment of comorbidities is also important.
Medications to treat gout attacks: Drugs used to treat acute attacks and prevent future attacks
include:
1. NSAIDs: NSAIDs are the usual first-line treatment for gout, and no specific agent is
significantly more or less effective than any other. Improvement may be seen within four
hours, and treatment is recommended for one to two weeks. They are not recommended,
however, in those with certain other health problems, such as gastrointestinal bleeding,
renal failure, or heart failure. While indomethacin has historically been the most
commonly used NSAID, an alternative, such as ibuprofen, may be preferred due to its
better side effect profile in the absence of superior effectiveness. For those at risk of
gastric side effects from NSAIDs, an additional proton pump inhibitor may be given.
2. Colchicine: Colchicine is an alternative for those unable to tolerate NSAIDs. Its side
effects (primarily gastrointestinal upset) limit its usage. Gastrointestinal upset, however,
depends on the dose, and the risk can be decreased by using smaller yet still effective
doses. Colchicine may interact with other commonly prescribed drugs, such as
atorvastatin and erythromycin, among others.
3. Steroids: Glucocorticoids have been found to be as effective as NSAIDs and may be
used if contraindications exist for NSAIDs. They also lead to improvement when injected
into the joint; a joint infection must be excluded, however, as steroids worsens this
condition.
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4. Pegloticase: Pegloticase (Krystexxa) was approved in the USA to treat gout in 2010. It
will be an option for the 3% of people who are intolerant to other medications.
Pegloticase is administered as an intravenous infusion every two weeks and has been
found to reduce uric acid levels in this population.
Medications to prevent gout complications: If you experience several gout attacks each year or
if your gout attacks are less frequent but particularly painful, your doctor may recommend
medication to reduce your risk of gout-related complications. Options include;
1. Medications that block uric acid production. Drugs called xanthine oxidase inhibitors,
including allopurinol (Aloprim, Lopurin, Zyloprim) and febuxostat (Uloric), limit the
amount of uric acid your body makes. This may lower your blood's uric acid level and
reduce your risk of gout. Side effects of allopurinol include a rash and low blood counts.
Febuxostat side effects include rash, nausea and reduced liver function. Xanthine oxidase
inhibitors may trigger a new, acute attack if taken before a recent attack has totally
resolved. Taking a short course of low-dose colchicine before starting a xanthine oxidase
inhibitor has been found to significantly reduce this risk.
2. Medication that improves uric acid removal. Probenecid (Probalan) improves your
kidneys' ability to remove uric acid from your body. This may lower your uric acid levels
and reduce your risk of gout, but the level of uric acid in your urine is increased. Side
effects include a rash, stomach pain and kidney stones.
Alternative medicines: If gout treatments aren't working as well as you'd hoped, you may be
interested in trying an alternative approach. Before trying such a treatment on your own, talk
with your doctor to weigh the benefits and risks and learn whether the treatment might interfere
with your gout medication. Because there isn't a lot of research on alternative therapies for gout,
however, in some cases the risks aren't known. Certain foods have been studied for their
potential to lower uric acid levels, including:
1. Coffee. Studies have found an association between coffee drinking both regular and
decaffeinated coffee and lower uric acid levels, though no study has demonstrated how or
why coffee may have such an effect.
2. Vitamin C. Supplements containing vitamin C may reduce the levels of uric acid in your
blood. However, vitamin C hasn't been studied as a treatment for gout. Don't assume that
if a little vitamin C is good for you, then lots is better. Megadoses of vitamin C may
increase your body's uric acid levels. Talk to your doctor about what a reasonable dose of
vitamin C may be. And don't forget that you can increase your vitamin C intake by eating
more fruits and vegetables, especially oranges.
3. Cherries. Cherries have been associated with lower levels of uric acid in studies, but it
isn't clear if they have any effect on gout signs and symptoms. Eating more cherries &
other dark-colored fruits, such as blackberries, blueberries, purple grapes and raspberries,
may be a safe way to supplement your gout treatment.
PREVENTION:
Guidelines for prevention are;
1. Apnea treatment: Gout may be secondary to sleep apnea via the release of purines from
oxygen-starved cells. Treatment of apnea can lessen the occurrence of attacks.
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2. Life style and diet control: During symptom-free periods, these dietary guidelines may
help protect against future gout attacks, these are;
i.
Keep your fluid intake high. Aim for 8 to 16 cups (about 2 to 4 liters) of fluid
each day, with at least half being water. Limit how many sweetened beverages
you drink, especially those sweetened with high fructose corn syrup.
ii.
Limit or avoid alcohol. Talk with your doctor about whether any amount or type
of alcohol is safe for you. Recent evidence suggests that beer may be particularly
likely to increase the risk of gout symptoms, especially in men.
iii. Eat a balanced diet following the Dietary Guidelines for Americans. Your
daily diet should emphasize fruits, vegetables, whole grains, and fat-free or lowfat milk products.
iv.
Get your protein from low-fat dairy products. Low-fat dairy products may
actually have a protective effect against gout, so these are your best-bet protein
sources.
v.
Limit your intake of meat, fish and poultry. A small amount may be tolerable,
but pay close attention to what types and how much seem to cause problems for
you.
vi.
Maintain a desirable body weight. Choose portions that allow you to maintain a
healthy weight. Losing weight may decrease uric acid levels in your body. But
avoid fasting or rapid weight loss, since doing so may temporarily raise uric acid
levels.
12.
DIABETES MELLITUS
INTRODUCTION:
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in
which a person has high blood sugar, either because the body does not produce enough insulin,
or because cells do not respond to the insulin that is produced. This high blood sugar produces
the classical symptoms of polyuria (frequent urination), polydipsia (increased thirst) and
polyphagia (increased hunger).
HISTORY
Diabetes was one of the first diseases described with an Egyptian manuscript from 1500 BC. The
first described cases are believed to be of type 1 diabetes. Indian physicians around the same
time identified the disease and classified it as madhumeha or "honey urine", noting the urine
would attract ants. The disease was considered as rare during the time of the Roman empire, with
Galen commenting he had only seen two cases during his career. This is possibly due the diet
and life-style of the ancient people, or because the clinical symptoms were observed during the
advanced stage of the disease. Galen named the disease "diarrhea of the urine" (diarrhea
urinosa).
Type 1 and type 2 diabetes where identified as separate conditions for the first time by the Indian
physicians Sushruta and Charaka in 400-500 AD with type 1 associated with youth and type 2
with being overweight. The term "mellitus" or "from honey" was added by the Briton John Rolle
in the late 1700s to separate the condition from diabetes insipidus, which is also associated with
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frequent urination. While many measure where tried, effective treatment was not developed until
the early part of the 20th century, when Canadians Frederick Banting and Charles Herbert Best
developed insulin in 1921 and 1922. This was followed by the development of the long-acting
insulin NPH in the 1940s.
CLASSIFICATION:
Diabetes mellitus is classified into four broad categories, type 1, type 2, gestational diabetes and
"other specific types". The "other specific types" are a collection of a few dozen individual
causes.
1. Type 1 diabetes: Type 1 diabetes mellitus is characterized by loss of the insulinproducing beta cells of the islets of Langerhans in the pancreas, leading to insulin
deficiency. This type can be further classified as immune-mediated or idiopathic. The
majority of type 1 diabetes is of the immune-mediated nature, in which beta cell loss is a
T-cell-mediated autoimmune attack. There is no known preventive measure against
type 1 diabetes, which causes approximately 10% of diabetes mellitus cases in North
America and Europe. Type 1 diabetes can affect children or adults, but was traditionally
termed "juvenile diabetes" because a majority of these diabetes cases were in children.
There are many different reasons for type 1 diabetes to be accompanied by irregular and
unpredictable hyperglycemias, frequently with ketosis, and sometimes serious
hypoglycemias, including an impaired counterregulatory response to hypoglycemia,
occult infection, gastroparesis (which leads to erratic absorption of dietary
carbohydrates), and endocrinopathies (e.g., Addison's disease).
2. Type 2 diabetes: Type 2 diabetes mellitus is characterized by insulin resistance, which
may be combined with relatively reduced insulin secretion. The defective responsiveness
of body tissues to insulin is believed to involve the insulin receptor. However, the
specific defects are not known. Diabetes mellitus cases due to a known defect are
classified separately. Type 2 diabetes is the most common type. In the early stage of
type 2, the predominant abnormality is reduced insulin sensitivity. At this stage,
hyperglycemia can be reversed by a variety of measures and medications that improve
insulin sensitivity or reduce glucose production by the liver.
3. Gestational diabetes: Gestational diabetes mellitus (GDM) resembles type 2 diabetes in
several respects, involving a combination of relatively inadequate insulin secretion and
responsiveness. It occurs in about 2%–5% of all pregnancies and may improve or
disappear after delivery. Gestational diabetes is fully treatable, but requires careful
medical supervision throughout the pregnancy.
4. Other types: Prediabetes indicates a condition that occurs when a person's blood glucose
levels are higher than normal but not high enough for a diagnosis of type 2 DM. Some
cases of diabetes are caused by the body's tissue receptors not responding to insulin; this
form is very uncommon. Genetic mutations (autosomal or mitochondrial) can lead to
defects in beta cell function. Diseases associated with excessive secretion of insulinantagonistic hormones can cause diabetes. Many drugs impair insulin secretion and some
toxins damage pancreatic beta cells.
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EPIDEMIOLOGY
Globally, as of 2010, an estimated 285 million people had diabetes, with type 2 making up about
90% of the cases. Its incidence is increasing rapidly, and by 2030, this number is estimated to
almost double. Diabetes mellitus occurs throughout the world, but is more common (especially
type 2) in the more developed countries. The greatest increase in prevalence is, however,
expected to occur in Asia and Africa, where most patients will probably be found by 2030. The
increase in incidence in developing countries follows the trend of urbanization and lifestyle
changes, perhaps most importantly a "Western-style" diet. This has suggested an environmental
(i.e., dietary) effect, but there is little understanding of the mechanism(s) at present, though there
is much speculation, some of it most compellingly presented.
ETIOLOGY:
However, diabetes is of two types, type 1 diabetes and type 2 diabetes, both of which differ in
their etiologies. The cause of diabetes depends on the type.
1. Etiology of Type 1 Diabetes: Type 1 diabetes is also known as childhood diabetes, insulin
dependent diabetes mellitus, or juvenile diabetes. This is a type of diabetes mellitus that
occurs due to the autoimmune destruction of the insulin producing beta cells of the pancreas.
The exact etiology of diabetes mellitus of this kind is not fully understood. It is said that
immunological factors, along with genetic and environmental factors are the cause behind
childhood diabetes symptoms. This is in fact a polygenic disease, that is, many different
genes contribute to its expression. The strongest gene, IDDM1, is located in the MHC class II
region on chromosome number 6, at staining region 6p21. This is believed to be responsible
for the histocompatibility disorder that is characteristic of type 1 insulin-producing beta cells
in the pancreas that display improper antigens to T cells. The etiology of diabetes can also
include strong environmental factors, as it has been seen that this strongly influences the
expression of type 1 diabetes.
2. Etiology of Type 2 Diabetes: Diabetes mellitus that affects people in adulthood is known as
type 2 diabetes, or non-insulin dependent diabetes or adult onset diabetes. This is a disorder
that is characterized by high levels of glucose in the blood that occurs due to an increase in
the resistance of the body to insulin. There are many factors that can lead to diabetes
mellitus, or at least that can exacerbate this type of diabetes. These factors include obesity
(around 55 percent of type 2 diabetes patients are obese at diagnosis), high blood pressure,
elevated cholesterol along with hyperlipidemia and with the condition often termed
metabolic syndrome. Other causes include acromegaly, Cushing's syndrome, thyrotoxicosis,
pheochromocytoma, chronic pancreatitis and the use of certain drugs. Additional factors
found to increase the risk of type 2 diabetes include aging and a diet that is high in fats along
with a sedentary lifestyle. There is also a possibly strong inheritable genetic connection in
type 2 diabetes. However, environmental factors like diet, weight and lifestyle play a large
part in the development of type 2 diabetes, in addition to any genetic component. There are
also many medications that can lead to the chronic onset and development of diabetes. These
include atypical anti-psychotic drugs, beta blockers, calcium channel blockers,
corticosteroids, phenothiazines, fluoroquinones, somatropin, protease inhibitors, thiazide
diuretics, etc.
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PATHOPHYSIOLOGY:
Following the consumption of food, carbohydrates are broken down into glucose molecules in
the gut. Glucose is absorbed into the bloodstream elevating blood glucose levels. This rise in
glycemia stimulates the secretion of insulin from the beta cells of the pancreas. Insulin is needed
by most cells to allow glucose entry. Insulin binds to specific cellular receptors and facilitates
entry of glucose into the cell, which uses the glucose for energy. The increased insulin secretion
from the pancreas and the subsequent cellular utilization of glucose results in lowered of blood
glucose levels. Lower glucose levels then result in decreased insulin secretion.
If insulin production and secretion are altered by disease, blood glucose dynamics will also
change. If insulin production is decreased, glucose entry into cells will be inhibited, resulting in
hyperglycemia. The same effect will be seen if insulin is secreted from the pancreas but is not
used properly by target cells. If insulin secretion is increased, blood glucose levels may become
very low (hypoglycemia) as large amounts of glucose enter tissue cells and little remains in the
bloodstream.
Excess glucose is stored in the liver in the form of glycogen, which serves as a ready reservoir
for future use. When energy is required, glycogen stores in the liver are converted into glucose
via glycogenolysis, elevating blood glucose levels and providing the needed cellular energy
source. The liver also produces glucose from fat (fatty acids) and proteins (amino acids) through
the process of gluconeogenesis. Glycogenolysis and gluconeogenesis both serve to increase
blood glucose levels. Thus, glycemia is controlled by a complex interaction between the
gastrointestinal tract, the pancreas, and the liver.
Multiple hormones may affect glycemia. Insulin is the only hormone that lowers blood glucose
levels. The counter-regulatory hormones such as glucagon, catecholamines, growth hormone,
thyroid hormone, and glucocorticoids all act to increase blood glucose levels, in addition to their
other effects.
Type 1 Diabetes: The underlying pathophysiologic defect in type 1 diabetes is an autoimmune
destruction of pancreatic beta cells. Following this destruction, the individual has an absolute
insulin deficiency and no longer produces insulin. Autoimmune beta cell destruction is thought
to be triggered by an environmental event, such as a viral infection. Genetically determined
susceptibility factors increase the risk of such autoimmune phenomena.
The onset of type 1 diabetes is usually abrupt. It generally occurs before the age of 30 years, but
may be diagnosed at any age. Most type 1 diabetic individuals are of normal weight or are thin in
stature. Since the pancreas no longer produces insulin, a type 1 diabetes patient is absolutely
dependent on exogenously administered insulin for survival. People with type 1 diabetes are
highly susceptible to diabetic ketoacidosis. Because the pancreas produces no insulin, glucose
cannot enter cells and remains in the bloodstream. Ketones are excreted in the urine,
accompanied by large amounts of water. The accumulation of ketones in body fluids, decreased
pH, electrolyte loss and dehydration from excessive urination, and alterations in the bicarbonate
buffer system result in diabetic ketoacidosis (DKA). Untreated DKA can result in coma or death.
Type 2 Diabetes: The underlying pathophysiologic defect in type 2 diabetes does not involve
autoimmune beta-cell destruction. Rather, type 2 diabetes is characterized by the following three
disorders:
i. Peripheral resistance to insulin, especially in muscle cells.
ii. Increased production of glucose by the liver.
iii. Altered pancreatic insulin secretion.
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Glucose cannot enter target cells and accumulates in the bloodstream, resulting in
hyperglycemia. The high blood glucose levels often stimulate an increase in insulin production
by the pancreas; thus, type 2 diabetic individuals often have excessive insulin production
(hyperinsulinemia). Hyperglycemia results in the urinary excretion of large amounts of glucose,
with attendant water loss. If fluids are not replaced, the dehydration can result in electrolyte
imbalance and acidosis.
Obesity contributes greatly to insulin
resistance, even in the absence of diabetes.
In fact, weight loss is a cornerstone of
therapy for obese type 2 diabetic patients.
Insulin resistance generally decreases
with weight loss. Obesity also may
explain the dramatic increase in the
incidence of type 2 diabetes among young
individuals in the United States in the past
10 to 20 years. Once considered a disease
of adults, type 2 diabetes has increased
among America's youth in direct correlation
with the increase in the average weight of children and
young adults during that time period.
Gestational Diabetes: Gestational diabetes usually develops during the third trimester and
significantly increases perinatal morbidity and mortality.The proper diagnosis and management
of gestational diabetes improves pregnancy outcomes. As with type 2 diabetes, the
pathophysiology of gestational diabetes is associated with increased insulin resistance. Most
patients with gestational diabetes return to a normoglycemic state after parturition; however,
about 30 to 50% of women with a history of gestational diabetes will develop type 2 diabetes
within 10 years.
COMPLICATIONS
Long-term complications of diabetes develop gradually, over years. Diabetes complications may
be disabling or even life-threatening.
1. Heart and blood vessel disease. Diabetes dramatically increases your risk of various
cardiovascular problems, including coronary artery disease with chest pain (angina), heart
attack, stroke, narrowing of the arteries (atherosclerosis) and high blood pressure. In fact,
about 65 percent of people who have type 1 or type 2 diabetes die of some type of heart or
blood vessel disease, according to the American Heart Association.
2. Nerve damage (neuropathy). Excess sugar can injure the walls of the tiny blood vessels
(capillaries) that nourish your nerves, especially in the legs. This can cause tingling,
numbness, burning or pain that usually begins at the tips of the toes or fingers and gradually
spreads upward. Poorly controlled blood sugar could cause you to eventually lose all sense of
feeling in the affected limbs. Damage to the nerves that affect the gastrointestinal tract can
cause problems with nausea, vomiting, diarrhea or constipation. For men, erectile
dysfunction may be an issue.
3. Kidney damage (nephropathy). The kidneys contain millions of tiny blood vessel clusters
that filter waste from your blood. Diabetes can damage this delicate filtering system. Severe
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damage can lead to kidney failure or irreversible end-stage kidney disease, requiring dialysis
or a kidney transplant.
4. Eye damage. Diabetes can damage the blood vessels of the retina (diabetic retinopathy),
potentially leading to blindness. Diabetes also increases the risk of other serious vision
conditions, such as cataracts and glaucoma.
5. Foot damage. Nerve damage in the feet or poor blood flow to the feet increases the risk of
various foot complications. Left untreated, cuts and blisters can become serious infections.
Severe damage might require toe, foot or even leg amputation.
6. Skin and mouth conditions. Diabetes may leave you more susceptible to skin problems,
including bacterial and fungal infections. Gum infections also may be a concern, especially if
you have a history of poor dental hygiene.
7. Osteoporosis. Diabetes may lead to lower than normal bone mineral density, increasing your
risk of osteoporosis.
8. Pregnancy complications. High blood sugar levels can be dangerous for both the mother
and the baby. The risk of miscarriage, stillbirth and birth defects are increased when diabetes
isn't well controlled. For the mother, diabetes increases the risk of diabetic ketoacidosis,
retinopathy, pregnancy-induced high blood pressure and preeclampsia.
9. Hearing problems. Hearing impairments occur more often in people with diabetes.
10. Alzheimer's disease. Type 2 diabetes may increase the risk of Alzheimer's disease and
vascular dementia. The poorer your blood sugar control, the greater the risk appears to be. So
what connects the two conditions? One theory is that cardiovascular problems caused by
diabetes could contribute to dementia by blocking blood flow to the brain or causing strokes.
Other possibilities are that too much insulin in the blood leads to brain-damaging
inflammation, or lack of insulin in the brain deprives brain cells of glucose.
SIGNS AND SYMPTOMS:
The classical symptoms of untreated diabetes are loss of weight, polyuria (frequent urination),
polydipsia (increased thirst) and polyphagia (increased hunger). Symptoms may develop rapidly
(weeks or months) in type 1 diabetes, while they usually develop much more slowly and may be
subtle or absent in type 2 diabetes. Prolonged high blood glucose can cause glucose absorption in
the lens of the eye, which leads to changes in its shape, resulting in vision changes. Blurred
vision is a common complaint leading to a diabetes diagnosis; type 1 should always be suspected
in cases of rapid vision change, whereas with type 2 change is generally more gradual, but
should still be suspected. A number of skin rashes that can occur in diabetes are collectively
known as diabetic dermadromes. People (usually with type 1 diabetes) may also present with
diabetic ketoacidosis, a state of metabolic dysregulation characterized by the smell of acetone, a
rapid, deep breathing known as Kussmaul breathing, nausea, vomiting and abdominal pain, and
altered states of consciousness.About 50 percent of people with type 2 diabetes don't experience
any symptoms and don't know they have the disease.
DIAGNOSIS:
Diabetes usually is diagnosed with the following tests that measure the glucose levels in your
blood, these are;
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1. Physical examinations: In the start of diagnosis with detail, check all sign and
symptoms. Check the B.P.
2. Glycated hemoglobin (A1C) test: This blood test indicates your average blood sugar
level for the past two to three months. It works by measuring the percentage of blood
sugar attached to hemoglobin, the oxygen-carrying protein in red blood cells. The higher
your blood sugar levels, the more hemoglobin you'll have with sugar attached. An A1C
level of 6.5 percent or higher on two separate tests indicates you have diabetes. A result
between 5.7 and 6.4 percent is considered prediabetes, which indicates a high risk of
developing diabetes.
3. Random blood sugar test: A blood sample will be taken at a random time. Blood sugar
values are expressed in milligrams per deciliter (mg/dL) or millimoles per liter (mmol/L).
Regardless of when you last ate, a random blood sugar level of 200 mg/dL (11.1 mmol/L)
or higher suggests diabetes, especially when coupled with any of the signs and symptoms
of diabetes, such as frequent urination and extreme thirst. A level between 140 mg/dL
(7.8 mmol/L) and 199 mg/dL (11.0 mmol/L) is considered prediabetes, which puts you at
greater risk of developing diabetes.
4. Fasting blood sugar test: A blood sample will be taken after an overnight fast. A fasting
blood sugar level less than 100 mg/dL (5.6 mmol/L) is normal. A fasting blood sugar
level from 100 to 125 mg/dL (5.6 to 6.9 mmol/L) is considered prediabetes. If it's 126
mg/dL (7 mmol/L) or higher on two separate tests, you have diabetes. A level from 100
mg/dL (5.6 mmol/L) to 125 mg/dL (6.9 mmol/L) is considered prediabetes.
MANAGEMENT:
Diabetes mellitus is a chronic disease which cannot be cured except in very specific situations.
Management concentrates on keeping blood sugar levels as close to normal ("euglycemia") as
possible, without causing hypoglycemia. This can usually be accomplished with diet, exercise,
and use of appropriate medications (insulin in the case of type 1 diabetes, oral medications, as
well as possibly insulin, in type 2 diabetes).Patient education, understanding, and participation is
vital, since the complications of diabetes are far less common and less severe in people who have
well-managed blood sugar levels. Drug therapy is given where necessary.
Lifestyle:
There are roles for patient education, dietetic support, sensible exercise, with the goal of keeping
both short-term and long-term blood glucose levels within acceptable bounds. In addition, given
the associated higher risks of cardiovascular disease, lifestyle modifications are recommended to
control blood pressure.
Medications:
Early initiation of pharmacologic therapy is associated with improved glycemic control and
reduced long-term complications in diabetes. Drug classes used for the treatment of diabetes
include the following:
1. Bigunids: Metformin is generally recommended as a first line treatment for type 2
diabetes, as there is good evidence that it decreases mortality. Metformin lowers basal
and postprandial plasma glucose levels. Its mechanisms of action differ from those of
other classes of oral antidiabetic agents; metformin works by decreasing hepatic
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2.
3.
4.
5.
6.
CLINICAL THERAPEUTICS
gluconeogenesis production. It also decreases intestinal absorption of glucose and
improves insulin sensitivity by increasing peripheral glucose uptake and utilization.
Unlike oral sulfonylureas, metformin rarely causes hypoglycemia.
Sulfonylureas: Sulfonylureas (eg, glyburide, glipizide, glimepiride) are insulin
secretagogues that stimulate insulin release from pancreatic beta cells and probably have
the greatest efficacy for glycemic lowering of any of the oral agents. However, that effect
is only short-term and quickly dissipates. Sulfonylureas may also enhance peripheral
sensitivity to insulin secondary to an increase in insulin receptors or to changes in the
events following insulin-receptor binding.
Meglitinide derivatives: Meglitinides (eg, repaglinide, nateglinide) are much shorteracting insulin secretagogues than the sulfonylureas are, with preprandial dosing
potentially achieving more physiologic insulin release and less risk for hypoglycemia.
Although meglitinides are considerably more expensive than sulfonylureas, they are
similar in their glycemic clinical efficacy.
Alpha-glucosidase inhibitors: These agents delay sugar absorption and help to prevent
postprandial glucose surges. Alpha-glucosidase inhibitors prolong the absorption of
carbohydrates, but their induction of flatulence greatly limits their use. They should be
titrated slowly to reduce gastrointestinal (GI) intolerance.
Thiazolidinediones: TZDs (eg, pioglitazone [Actos], rosiglitazone [Avandia]) act as
insulin sensitizers; thus, they require the presence of insulin to work. They must be taken
for 12-16 weeks to achieve maximal effect. These agents are used as monotherapy or in
combination with sulfonylurea, metformin, meglitinide, DPP-4 inhibitors, GLP-1
receptor agonists, or insulin. They are the only antidiabetic agents that have been shown
to slow the progression of diabetes (particularly in early disease).
Insulin: Type 1 diabetes is typically treated with a combinations of regular and NPH
insulin, or synthetic insulin analogs. When insulin is used in type 2 diabetes, a longacting formulation is usually added initially, while continuing oral medications. Doses of
insulin are then increased to effect. People with type 1 diabetes require multiple insulin
injections each day to maintain safe insulin levels. Insulin is often required to treat type 2
diabetes too. Using an insulin pump is an alternative to injections. The pump is about the
size of a pager and is usually worn on your belt. Insulin is delivered through a small tube
(catheter) that is placed under the skin (usually in the abdomen). There are four major
types of insulin:
 Rapid-acting
 Short-acting
 Intermediate-acting
 Long-acting
Your doctor will determine your dose and how often you need to take insulin. There is no
standard insulin dose as it depends on factors such as your body weight, when you eat,
how often you exercise and how much insulin your body produces.
PREVENTION:
Guidelines from the American College of Clinical Endocrinologists for the prevention of
diabetes mellitus in patients at risk recommend the following measures:
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1. Life Style improvement: Healthy lifestyle choices can help you prevent type 2 diabetes.
Even if diabetes runs in your family, diet and exercise can help you prevent the disease. If
you've already been diagnosed with diabetes, the same healthy lifestyle choices can help you
prevent potentially serious complications. And if you have prediabetes, lifestyle changes can
slow or halt the progression from prediabetes to diabetes.
 Eat healthy foods: Choose foods low in fat and calories. Focus on fruits, vegetables
and whole grains. For every 1,000 calories you consume, try to have at least 14 grams
of fiber, because fiber helps control blood sugar levels.
 Get physical: Aim for 30 minutes of moderate physical activity a day. Take a brisk
daily walk. Ride a bike. Swim laps. If you can't fit in a long workout, spread 10minute or longer sessions throughout the day.
 Lose excess pounds: If you're overweight, losing 5 to 10 percent of your body weight
can reduce the risk of diabetes. To keep your weight in a healthy range, focus on
permanent changes to your eating and exercise habits. Motivate yourself by
remembering the benefits of losing weight, such as a healthier heart, more energy and
improved self-esteem.
2. Drinking Coffee: There's some evidence that coffee and, possibly, tea drinking may
decrease your risk of developing type 2 diabetes, but more research is needed.
3. Medications: Many of the drugs are used to prevent diabetes, but FDA not recommanded
medications before diabetes.
13. HYPERTENSION
INTRODUCTION:
Hypertension (HTN) or high blood pressure, sometimes called arterial hypertension, is a
chronic medical condition in which the blood pressure in the arteries is elevated. This requires
the heart to work harder than normal to circulate blood through the blood vessels. Blood pressure
involves two measurements, systolic and diastolic, which depend on whether the heart muscle is
contracting (systole) or relaxed between beats (diastole). Blood pressure measurements fall into
four general categories:
a) Normal blood pressure: Your blood pressure is normal if it's below 120/80 mm Hg.
However, some doctors recommend 115/75 mm Hg as a better goal. Once blood pressure
rises above 115/75 mm Hg, the risk of cardiovascular disease begins to increase.
b) Prehypertension: Prehypertension is a systolic pressure ranging from 120 to 139 mm Hg
or a diastolic pressure ranging from 80 to 89 mm Hg. Prehypertension tends to get worse
over time.
c) Stage 1 hypertension: Stage 1 hypertension is a systolic pressure ranging from 140 to
159 mm Hg or a diastolic pressure ranging from 90 to 99 mm Hg.
d) Stage 2 hypertension: More severe hypertension, stage 2 hypertension is a systolic
pressure of 160 mm Hg or higher or a diastolic pressure of 100 mm Hg or higher.
EPIDEMIOLOGY:
As of 2000, nearly one billion people or ~26% of the adult population of the world had
hypertension. It was common in both developed (333 million) and undeveloped (639 million)
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countries. However rates vary markedly in different regions with rates as low as 3.4% (men) and
6.8% (women) in rural India and as high as 68.9% (men) and 72.5% (women) in Poland.
In 1995 it was estimated that 43 million people in the United States had hypertension or were
taking antihypertensive medication, almost 24% of the adult United States population. The
prevalence of hypertension in the United States is increasing and reached 29% in 2004. As of
2006 hypertension affects 76 million US adults (34% of the population) and African American
adults have among the highest rates of hypertension in the world at 44%. It is more common in
blacks and native Americans and less in whites and Mexican Americans, rates increase with age,
and is greater in the southeastern United States. Hypertension is more prevalent in men (though
menopause tends to decrease this difference) and in those of low socioeconomic status.
The prevalence of high blood pressure in the young is increasing. Most childhood hypertension,
particularly in preadolescents, is secondary to an underlying disorder. Aside from obesity, kidney
disease is the most common (60–70%) cause of hypertension in children. Adolescents usually
have primary or essential hypertension, which accounts for 85–95% of cases.
ETIOLOGY:
The different causes are;
1. Primary hypertension: Primary (essential) hypertension is the most common form of
hypertension, accounting for 90–95% of all cases of hypertension. Numerous common genes
with small effects on blood pressure have been identified as well as some rare genes with
large effects on blood pressure but the genetic basis of hypertension is still poorly
understood. Several environmental factors influence blood pressure. Lifestyle factors that
lower blood pressure, include reduced dietary salt intake, increased consumption of fruits and
low fat products (Dietary Approaches to Stop Hypertension (DASH diet)), exercise, weight
loss and reduced alcohol intake. The possible role of other factors such as stress, caffeine
consumption, and vitamin D deficiency are less clear cut. Insulin resistance, which is
common in obesity and is a component of syndrome X (or the metabolic syndrome), is also
thought to contribute to hypertension. Recent studies have also implicated events in early life
(for example low birth weight, maternal smoking and lack of breast feeding) as risk factors
for adult essential hypertension, although the mechanisms linking these exposures to adult
hypertension remain obscure.
2. Secondary hypertension: Secondary hypertension results from an identifiable cause. Renal
disease is the most common secondary cause of hypertension. Hypertension can also be
caused by endocrine conditions, such as Cushing's syndrome, hyperthyroidism,
hypothyroidism, acromegaly, Conn's syndrome or hyperaldosteronism, hyperparathyroidism
and pheochromocytoma. Other causes of secondary hypertension include obesity, sleep
apnea, pregnancy, coarctation of the aorta, excessive liquorice consumption and certain
prescription medicines, herbal remedies and illegal drugs.
PATHOPHYSIOLOGY:
In most people with established essential (primary) hypertension, increased resistance to blood
flow (total peripheral resistance) accounting for the high pressure while cardiac output remains
normal. There is evidence that some younger people with prehypertension or 'borderline
hypertension' have high cardiac output, an elevated heart rate and normal peripheral resistance,
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termed hyperkinetic borderline hypertension. These individuals develop the typical features of
established essential hypertension in later life as their cardiac output falls and peripheral
resistance rises with age. Whether this pattern is typical of all people who ultimately develop
hypertension is disputed. The increased peripheral resistance in established hypertension is
mainly attributable to structural narrowing of small arteries and arterioles, although a reduction
in the number or density of capillaries may also contribute. Hypertension is also associated with
decreased peripheral venous compliance which may increase venous return, increase cardiac
preload and, ultimately, cause diastolic dysfunction. Whether increased active vasoconstriction
plays a role in established essential hypertension is unclear.
Pulse pressure (the difference between systolic and diastolic blood pressure) is frequently
increased in older people with hypertension. This can mean that systolic pressure is abnormally
high, but diastolic pressure may be normal or low, a condition termed isolated systolic
hypertension. The high pulse pressure in elderly people with hypertension or isolated systolic
hypertension is explained by increased arterial stiffness, which typically accompanies aging and
may be exacerbated by high blood pressure.
Many mechanisms have been proposed to account for the rise in peripheral resistance in
hypertension. Most evidence implicates either:
1. Disturbances in renal salt and water handling, particularly abnormalities in the intrarenal
renin-angiotensin system.
2. Abnormalities of the sympathetic nervous system.
These mechanisms are not mutually exclusive and it is likely that both contribute to some extent
in most cases of essential hypertension. It has also been suggested that endothelial dysfunction
and vascular inflammation may also contribute to increased peripheral resistance and vascular
damage in hypertension.
COMPLICATIONS:
The excessive pressure on your artery walls caused by high blood pressure can damage blood
vessels, as well as organs in the body. The higher your blood pressure and the longer it goes
uncontrolled, the greater the damage. Uncontrolled high blood pressure can lead to:
1. Heart attack or stroke: High blood pressure can cause hardening and thickening of the
arteries (atherosclerosis), which can lead to a heart attack, stroke or other complications.
2. Aneurysm: Increased blood pressure can cause your blood vessels to weaken and bulge,
forming an aneurysm. If an aneurysm ruptures, it can be life-threatening.
3. Heart failure: To pump blood against the higher pressure in your vessels, your heart
muscle thickens. Eventually, the thickened muscle may have a hard time pumping enough
blood to meet your body's needs, which can lead to heart failure.
4. Weakened and narrowed blood vessels in your kidneys: This can prevent these organs
from functioning normally and causes nephropathy.
5. Thickened, narrowed or torn blood vessels in the eyes: This can result in vision loss
(retinopathy).
6. Metabolic syndrome: This syndrome is a cluster of disorders of your body's metabolism
including increased waist circumference, high triglycerides, low high-density lipoprotein
(HDL), or "good," cholesterol, high blood pressure, and high insulin levels. If you have high
blood pressure, you're more likely to have other components of metabolic syndrome. The
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more components, the greater your risk of developing diabetes, heart disease or stroke.
7. Trouble with memory or understanding: Uncontrolled high blood pressure may also
affect ability to think, remember and learn. Trouble with memory or understanding concepts
is more common in people who have high blood pressure.
SIGNS AND SYMPTOMS:
A proportion of people with high blood pressure reports headaches (particularly at the back of
the head and in the morning), as well as lightheadedness, vertigo, tinnitus (buzzing or hissing in
the ears), altered vision or fainting episodes, neck pain, polyuria and left ventricular hypertrophy
etc.. Some additional signs and symptoms may suggest secondary hypertension, i.e. hypertension
due to an identifiable cause such as kidney diseases or endocrine diseases. Labile or paroxysmal
hypertension accompanied by headache, palpitations, pallor, and perspiration should prompt
suspicions of pheochromocytoma. Failure to thrive, seizures, irritability, lack of energy, and
difficulty breathing can be associated with hypertension in neonates and young infants. In older
infants and children, hypertension can cause headache, unexplained irritability, fatigue, failure to
thrive, blurred vision, nosebleeds, and facial paralysis.
DIAGNOSIS:
1. Complete history and physical examination: Initial assessment of the hypertensive
people should include a complete history and physical examination. With the availability of
24-hour ambulatory blood pressure monitors and home blood pressure machine.
Hypertension is diagnosed on the basis of a persistently high blood pressure. Traditionally,
this requires three separate sphygmomanometer measurements at one monthly intervals.
2. Laboratory tests: It can also be performed to identify possible causes of secondary
hypertension, and to determine whether hypertension has caused damage to the heart, eyes,
and kidneys. Additional tests for diabetes and high cholesterol levels are usually performed
because these conditions are additional risk factors for the development of heart disease
and may require treatment.
a) Urine analysis: Testing of urine samples for protein is used as a secondary indicator of
kidney disease.
b) ECG: Electrocardiogram (EKG/ECG) testing is done to check for evidence that the
heart is under strain from high blood pressure. It may also show whether there is
thickening of the heart muscle (left ventricular hypertrophy) or whether the heart has
experienced a prior minor disturbance such as a silent heart attack.
c) Chest X-ray: Chest X-ray or an echocardiogram may also be performed to look for
signs of heart enlargement or damage to the heart.
d) Blood tests: These are; random blood sugar, fasting blood sugar, serum creatinine,
lapide profile analysis, renin test and blood aldesterone test.
MANAGEMENT:
Lifestyle modifications:
The first line of treatment for hypertension is identical to the recommended preventative lifestyle
changes and includes: dietary changes, physical exercise, and weight loss. These have all been
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shown to significantly reduce blood pressure in people with hypertension. If hypertension is high
enough to justify immediate use of medications, lifestyle changes are still recommended in
conjunction with medication. Different programs aimed to reduce psychological stress such as
biofeedback, relaxation or meditation are advertised to reduce hypertension. However, in general
claims of efficacy are not supported by scientific studies, which have been in general of low
quality. A diet rich in nuts, whole grains, fish, poultry, fruits (peach) and vegetables promoted in
the USA by the National Heart, Lung, and Blood Institute lowers blood pressure. A major feature
of the plan is limiting intake of sodium, although the diet is also rich in potassium, magnesium,
calcium, as well as protein.
Medications:
Guidelines on the choice of agents and how to best to step up treatment for various subgroups
have changed over time and differ between countries. The best first line agent is disputed. The
Cochrane collaboration, World Health Organization and the United States guidelines supports
low dose thiazide-based diuretic as first line treatment. The UK guidelines emphasise calcium
channel blockers (CCB) in preference for people over the age of 55 years or if of African or
Caribbean family origin, with angiotensin converting enzyme inhibitors (ACE-I) used first line
for younger people. These medications are;
1. Thiazide diuretics. Diuretics, sometimes called water pills, are medications that act on
your kidneys to help your body eliminate sodium and water, reducing blood volume.
Thiazide diuretics are often the first but not the only choice in high blood pressure
medications. If you're not taking a diuretic and your blood pressure remains high, talk to
your doctor about adding one or replacing a drug you currently take with a diuretic.
2. Beta blockers. These medications reduce the workload on your heart and open your
blood vessels, causing your heart to beat slower and with less force. When prescribed
alone, beta blockers don't work as well in blacks or in older adults but they're effective
when combined with a thiazide diuretic.
3. Angiotensin-converting enzyme (ACE) inhibitors. These medications help relax blood
vessels by blocking the formation of a natural chemical that narrows blood vessels.
4. Angiotensin II receptor blockers (ARBs). These medications help relax blood vessels
by blocking the action not the formation of a natural chemical that narrows blood vessels.
5. Calcium channel blockers. These medications help relax the muscles of blood vessels.
Some slow down heart rate. Calcium channel blockers may work better for blacks and
older adults than do ACE inhibitors or beta blockers alone. A word of caution for
grapefruit lovers, though. Grapefruit juice interacts with some calcium channel blockers,
increasing blood levels of the medication and putting you at higher risk of side effects.
Talk to your doctor or pharmacist if you're concerned about interactions.
6. Renin inhibitors. Aliskiren (Tekturna) slows down the production of renin, an enzyme
produced by your kidneys that starts a chain of chemical steps that increases blood
pressure. Tekturna works by reducing the ability of renin to begin this process. Due to a
risk of serious complications, including stroke, you shouldn't take aliskiren with ACE
inhibitors or ARBs.
If you're having trouble reaching your blood pressure goal with combinations of the above
medications, doctor may prescribe:
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1. Alpha blockers. These medications reduce nerve impulses to blood vessels, reducing the
effects of natural chemicals that narrow blood vessels.
2. Alpha-beta blockers. In addition to reducing nerve impulses to blood vessels, alpha-beta
blockers slow the heartbeat to reduce the amount of blood that must be pumped through
the vessels.
3. Central-acting agents. These medications prevent the brain from signaling your nervous
system to increase your heart rate and narrow your blood vessels.
4. Vasodilators. These medications work directly on the muscles in the walls of your
arteries, preventing the muscles from tightening and your arteries from narrowing.
Once your blood pressure is under control, doctor may have you take a daily aspirin to reduce
your risk of cardiovascular disorders.
Drug combinations: The majority of people require more than one drug to control their
hypertension. JNC7 and ESH-ESC guidelines advocate starting treatment with two drugs when
blood pressure is >20 mmHg above systolic or >10 mmHg above diastolic targets. Preferred
combinations are renin–angiotensin system inhibitors and calcium channel blockers, or renin–
angiotensin system inhibitors and diuretics. Acceptable combinations include calcium channel
blockers and diuretics, beta-blockers and diuretics, dihydropyridine calcium channel blockers
and beta-blockers, or dihydropyridine calcium channel blockers with either verapamil or
diltiazem. Unacceptable combinations are non-dihydropyridine calcium blockers (such as
verapamil or diltiazem) and beta-blockers, dual renin–angiotensin system blockade (e.g.
angiotensin converting enzyme inhibitor + angiotensin receptor blocker), renin–angiotensin
system blockers and beta-blockers, beta-blockers and anti-adrenergic drugs. Combinations of an
ACE-inhibitor or angiotensin II–receptor antagonist, a diuretic and an NSAID (including
selective COX-2 inhibitors and non-prescribed drugs such as ibuprofen) should be avoided
whenever possible due to a high documented risk of acute renal failure. The combination is
known colloquially as a "triple whammy" in the Australian health industry. Tablets containing
fixed combinations of two classes of drugs are available and while convenient for the people,
may be best reserved for those who have been established on the individual components.
PREVENTION:
Much of the disease burden of high blood pressure is experienced by people who are not labelled
as hypertensive. Consequently, population strategies are required to reduce the consequences of
high blood pressure and reduce the need for antihypertensive drug therapy. Lifestyle changes are
recommended to lower blood pressure, before starting drug therapy. Following are guidlines for
prevention, these are;
a) Maintain normal body weight for adults (e.g. body mass index 20–25 kg/m2).
b) Reduce dietary sodium intake to <100 mmol/ day (<6 g of sodium chloride or <2.4 g of
sodium per day).
c) Engage in regular aerobic physical activity such as brisk walking (≥30 min per day, most days
of the week).
d) Limit alcohol consumption to no more than 3 units/day in men and no more than 2 units/day
in women
e) Consume a diet rich in fruit and vegetables (e.g. at least five portions per day);
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