PATHOPHYSIOLOGY OF MENINGITIS

DEFINITION: Meningitis is an acute inflammation of the protective membranes

covering the brain and spinal cord, collectively known as the meninges.

SIGNS AND SYMPTOMS:

Early meningitis symptoms may mimic the flu (influenza). Symptoms may develop
over several hours or over a few days.

Possible signs and symptoms in anyone older than the age of 2 include:

 Sudden high fever * Stiff neck * Seizures

 Skin rashes * Sensitivity to light * No appetite or thirst
 Confusion or difficulty concentrating
 Sleepiness or difficulty waking
 Severe headache that seems different than normal
 Headache with nausea or vomiting
Signs in newborns

 High fever * Constant crying

 Inactivity or sluggishness *Poor feeding
 A bulge in the soft spot on top of a baby's head (fontanel)
 Stiffness in a baby's body and neck
 Excessive sleepiness or irritability
Mode of spread : The bacteria are transmitted from person-to-person through droplets
of respiratory or throat secretions from carriers. Smoking, close and prolonged contact
– such as kissing, sneezing or coughing on someone, or living in close quarters with a
carrier – facilitates the spread of the disease.

EPIDEMIOLOGY: Although meningitis is a notifiable disease in many countries, the

exact incidence rate is unknown. In 2013 meningitis resulted in 303,000 deaths – down
from 464,000 deaths in 1990. In 2010 it was estimated that meningitis resulted in
420,000 deaths. excluding cryptococcal meningitis.

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 ETIOLOGY:

Viral infections are the most common cause of meningitis, followed by bacterial
infections and, rarely, fungal infections. Because bacterial infections can be life-
threatening, identifying the cause is essential.

Bacterial meningitis: Bacteria that enter the bloodstream and travel to the brain and
spinal cord cause acute bacterial meningitis. But it can also occur when bacteria
directly invade the meninges. This may be caused by an ear or sinus infection, a skull
fracture, or, rarely, after some surgeries.

Several strains of bacteria can cause acute bacterial meningitis, most commonly:

Streptococcus pneumoniae (pneumococcus). This bacterium is the most common

cause of bacterial meningitis in infants, young children and adults in the United States.
It more commonly causes pneumonia or ear or sinus infections. A vaccine can help
prevent this infection.

Neisseria meningitidis (meningococcus). This bacterium is another leading cause of

bacterial meningitis. These bacteria commonly cause an upper respiratory infection but
can cause meningococcal meningitis when they enter the bloodstream. This is a highly
contagious infection that affects mainly teenagers and young adults. It may cause local
epidemics in college dormitories, boarding schools and military bases. A vaccine can
help prevent infection.

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Haemophilus influenzae (haemophilus). Haemophilus influenzae type b (Hib)
bacterium was once the leading cause of bacterial meningitis in children. But new Hib
vaccines have greatly reduced the number of cases of this type of meningitis.

Listeria monocytogenes (listeria). These bacteria can be found in unpasteurized

cheeses, hot dogs and lunchmeats. Pregnant women, newborns, older adults and people
with weakened immune systems are most susceptible. Listeria can cross the placental
barrier, and infections in late pregnancy may be fatal to the baby.
Viral meningitis: Viral meningitis is usually mild and often clears on its own. Most
cases in the United States are caused by a group of viruses known as enteroviruses,
which are most common in late summer and early fall. Viruses such as herpes simplex
virus, HIV, mumps, West Nile virus and others also can cause viral meningitis.

Chronic meningitis: Slow-growing organisms (such as fungi and Mycobacterium

tuberculosis) that invade the membranes and fluid surrounding your brain cause
chronic meningitis. Chronic meningitis develops over two weeks or more. The signs
and symptoms of chronic meningitis — headaches, fever, vomiting and mental
cloudiness — are similar to those of acute meningitis.

Fungal meningitis: Fungal meningitis is relatively uncommon and causes chronic

meningitis. It may mimic acute bacterial meningitis. Fungal meningitis isn't contagious
from person to person. Cryptococcal meningitis is a common fungal form of the disease
that affects people with immune deficiencies, such as AIDS. It's life-threatening if not
treated with an antifungal medication.

Other meningitis causes: Meningitis can also result from noninfectious causes, such
as chemical reactions, drug allergies, some types of cancer and inflammatory diseases
such as sarcoidosis.

Risk factors

 Skipping vaccinations. Risk rises for anyone who hasn't completed the
recommended childhood or adult vaccination schedule.
 Age. Most cases of viral meningitis occur in children younger than age 5. Bacterial
meningitis is common in those under age 20.
 Living in a community setting. College students living in dormitories, personnel
on military bases, and children in boarding schools and child care facilities are at
greater risk of meningococcal meningitis. This is probably because the bacterium
is spread by the respiratory route, and spreads quickly through large groups.

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  Pregnancy. Pregnancy increases the risk of listeriosis — an infection caused by
listeria bacteria, which may also cause meningitis. Listeriosis increases the risk of
miscarriage, stillbirth and premature delivery.
 Compromised immune system. AIDS, alcoholism, diabetes, use of
immunosuppressant drugs and other factors that affect your immune system also
make you more susceptible to meningitis. Having your spleen removed also
increases your risk, and anyone without a spleen should get vaccinated to
minimize that risk.
Complications: Meningitis complications can be severe. The longer you or your child
has the disease without treatment, the greater the risk of seizures and permanent
neurological damage, including:

 Hearing loss * Memory difficulty

 Learning disabilities * Brain damage
 Gait problems * Seizures
 Kidney failure * Shock * Death
Diagnosis

Blood cultures. Blood samples are placed in a special dish to see if it grows
microorganisms, particularly bacteria. A sample may also be placed on a slide and
stained (Gram's stain), then studied under a microscope for bacteria.

Imaging. Computerized tomography (CT) or magnetic resonance imaging (MRI) scans

of the head may show swelling or inflammation. X-rays or CT scans of the chest or
sinuses also may show infection in other areas that may be associated with meningitis.
Spinal tap (lumbar puncture). For a definitive diagnosis of meningitis, you'll need a
spinal tap to collect cerebrospinal fluid (CSF). In people with meningitis, the CSF often
shows a low sugar (glucose) level along with an increased white blood cell count and
increased protein.
CSF analysis may also help your doctor identify which bacterium caused the
meningitis. If your doctor suspects viral meningitis, he or she may order a DNA-based
test known as a polymerase chain reaction (PCR) amplification or a test to check for
antibodies against certain viruses to determine the specific cause and determine proper
treatment.

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PATHOGENESIS:

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 PATHOPHYSIOLOGY OF TYPHOID

DEFINITION: Typhoid fever, also called typhoid, acute infectious disease caused by
the bacterium Salmonella enterica serovar Typhi. The bacterium usually enters the
body through the mouth by the ingestion of contaminated food or water, penetrates the
intestinal wall, and multiplies in lymphoid tissue; it then enters the bloodstream and
causes bacteremia.

No animals carry this disease, so transmission is always human to human.

Sign and Symptoms

1. Salmonella infection is more common in children less than 10 years of age.

2. Prodromal stage = malaise, headache, cough, sore throat, abdominal pain, and
constipation.
1. Diarrhea is late symptoms and is usually in the third week of illness.
3. Fever = constant and ascends in a stepwise pattern.
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 4. 7 to 10 days = Paek and patients are sicker.
1. Early diarrhea.
2. Abdominal distension.
5. Patients improve after 7 to 10 days.
1. Untreated cases recover in about 4 weeks.
2. Symptoms disappear with antibiotics within 3 to 4 days.
6. Relapse may occur after 2 weeks.
7. Gastroenteritis incubation period is 8 to 24 hours.
1. There are nausea and vomiting.
2. There is abdominal pain.
3. There is diarrhea.
4. There may be a fever.
5. This is self-limiting disease and recovery is usually within a week.

Pathophysiology

1. Salmonella is found in humans as well as in chickens and eggs.

2. Enteric fever includes typhoid and paratyphoid fever.
1. Paratyphoid fever is generally mild than typhoid fever.
3. Typhoid fever is caused by the Salmonella species.
4. Salmonella has three antigens:
1. O antigen is present in the body of bacteria.
1. This resists alcohol extraction and is thermostable.
2. H antigen is present in the flagella of the bacteria.
3. Vi antigen is most superficial of the somatic antigen of S. Typhi.

5. Mode of spread by the:

1. Contaminated food (including meat).

2. Contaminated water supply.

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6. The incubation period is 5 to 14 days and sometimes is longer.
7. Pathogenesis:
1. There are three types of disease:
1. Enteric fever.
2. Gastroenteritis.
3. Septicemia.
2. This organism crosses the intestinal epithelium then multiply in the
macrophagic cells of Peyer's patches, mesenteric lymph nodes, and
spleen.
3. Peyer’s patches inflamed may ulcerate.
4. Bacteremia occurs and the infection spread to lungs ,
gallbladder, kidneys, and CNS.

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Complications:

1. Relapse.
2. Intestinal Perforation.
3. Hemorrhage in the GIT.
4. Myocarditis.
5. The lungs may show pneumonia picture.
6. Rarely periostitis.

Lab Diagnosis

1. CBC shows: Low TLC, leucopenia.

2. Blood culture, positive in the first week of infection in 80 % of the cases. But
blood culture may reach 90 % of the cases and it decreases to 50% in the third
week.
1. Blood culture is positive in the 80% of the cases in the first week of
infection.
2. Blood culture is considered 100 % specific.
3. Buffy coat may decrease the time for isolation.
4. This is subcultured on the MacConkey media.
3. Bone marrow culture if taken will be positive and may have high yield up to
90% sensitivity.
4. Stool culture will be a positive but not reliable test. This will be positive within
the first 7 days of infection.
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 1. This is negative in 60 to 70% of the cases during the first week. If the
patient is untreated then positive in these patients in the third week.
2. The chronic carrier may have stool culture positive even up to one year.
3. Feces cultures on solid selective media:
1. Desoxycholate citrate agar where there are non-lactose fermenting
colonies.
2. Macconkey medium shows non-fermenting colonies.
3. There is no gas and no fermentation of the sugar.

5. Widal test will be positive after 7 to 10 days of infection.

6. Typhidot test claimed by the manufacturing companies that it will be positive

after 2 to 3 days.

7. The urine culture may be done and is positive in case of enteric fever but is less
sensitive.
1. This is positive in the third or fourth week of the infection.
2. This is done on the MacConkey media.

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 8. Bacteriophage typing is done to identify the different strains of S.typhi and also
Paratyphi.
1. This is useful for the epidemiological investigation in case of the source of
the outbreak.

Summary of the available lab tests:

Treatment

1. The drug of choice is the Ciprofloxacin.

2. Chloramphenicol is also effective but this may have a serious side effect.
3. Co-trimoxazole is also used and has less serious side effect like
Chloramphenicol.

PATHOPHYSIOLOGY OF LEPROSY

DEFINITION: A chronic infectious disease caused by a mycobacterium

(Mycobacterium leprae) affecting especially the skin and peripheral nerves and
characterized by the formation of nodules or macules that enlarge and spread
accompanied by loss of sensation with eventual paralysis, wasting of muscle, and
production of deformities.
— called also Hansen's disease

CAUSES:
Leprosy is caused mainly by an "acid fast" bacterium Mycobacterium leprae, a rod-
shaped slow-growing bacillus that is an obligate intracellular (only grows inside of
certain human and animal cells) bacterium.
SIGNS & SYMPTOMS:
The disease can cause skin symptoms such as:
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  Discolored patches of skin, usually flat, that may be numb and look faded
(lighter than the skin around)
 Growths (nodules) on the skin
 Thick, stiff or dry skin
 Painless ulcers on the soles of feet
 Painless swelling or lumps on the face or earlobes
 Loss of eyebrows or eyelashes

Symptoms caused by damage to the nerves are:

 Numbness of affected areas of the skin

 Muscle weakness or paralysis (especially in the hands and feet)
 Enlarged nerves (especially those around the elbow and knee and in the sides of
the neck)
 Eye problems that may lead to blindness (when facial nerves are affected)

Symptoms caused by the disease in the mucous membranes are:

 A stuffy nose
 Nosebleeds

Mode of spread:
Transmission of leprosy occurs during close contact with those who are infected.
Transmission is proposed to be by nasal droplets, but many questions remain about its
mode of transmission and epidemiology. Leprosy is not known to be either sexually
transmitted or highly infectious. People are generally no longer infectious after the first
month of standard multidrug therapy. Leprosy may also be transmitted to humans
by armadillos, although the mechanism is not fully understood.

TYPER OF LEPROSY:

Classification Symptoms Disease response

Tuberculoid leprosy
Borderline tuberculoid
leprosy
Mid-borderline leprosy
Borderline lepromatous
leprosy
A few flat lesions, some
large and numb; some
nerve involvement
Lesions similar to
tuberculoid but more
numerous; more nerve
involvement
Reddish plaques; moderate
numbness; swollen lymph
nodes; more nerve
involvement
Many lesions, including
flat lesions, raised bumps,
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Can heal on its own,
persist, or may progress to
a more severe form
May persist, revert to
tuberculoid, or advance to
another form
May regress, persist, or
progress to other forms
May persist, regress, or
progress

Lepromatous leprosy
plaques, and nodules; more
numbness
Many lesions with bacteria; Doesn’t regress
hair loss; more severe
nerve involvement with
peripheral nerve
thickening; limb weakness;
disfigurement

RISK FACTORS:
 Close Contact
 Immunosuppresion
 Armadillo Contact
 Genetic Risk Factors
 Age (between the ages of 5 and 15 years )
 Endemic Regions

 Angola * Brazil * India * Nepal

 Madagascar * Mozambique * Kiribati
 Central African Republic
 Democratic Republic of Congo
 Federated States of Micronesia
 Republic of Marshall Islands
 United Republic of Tanzania
 Tattooing
 Vertical Transmission from Mother

COMPLICATIONS: Delayed diagnosis and treatment can lead to serious

complications. These can include:

 Disfigurement
 Hair loss, particularly on the eyebrows and eyelashes
 muscle weakness
 permanent nerve damage in the arms and legs
 Inability to use hands and feet
 Chronic nasal congestion, nosebleeds and collapse of the nasal septum
 Iritis * Glaucoma * Blindness
 Erectile dysfunction (ED) * Infertility * Kidney failure
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PATHOGENESIS: Onset of leprosy is insidious. It affects nerves, skin and eyes. It
may also affect mucosa (mouth, nose, pharynx), testes, kidney, voluntary/smooth
muscles, reticulo-endothelial system, and vascular endothelium.

Bacilli enter the body usually through respiratory system. It has low
pathogenicity, only a small proportion of infected people develop signs of the
disease. Though infected, majority of the population do not develop the disease.
After entering the body, bacilli migrate towards the neural tissue and enter the
Schwann cells. Bacteria can also be found in, macrophages, muscle cells and
endothelial cells of blood vessels.

After entering the Schwann cells /macrophage; fate of the bacterium depends on
the resistance of the infected individual towards the infecting organism. Bacilli
start multiplying slowly (about 12-14 days for one bacterium to divide into two)
within the cells, get liberated from the destroyed cells and enter other unaffected
cells. Till this stage person remains free from signs and symptoms of leprosy.

As the bacilli multiply, bacterial load increases in the body and infection is
recognized by the immunological system. Lymphocytes and histiocytes
(macrophages) invade the infected tissue. At this stage clinical manifestation may
appear as involvement of nerves with impairment of sensation &/ or skin patch. If
it is not diagnosed and treated in the early stages, further progress of the diseases
is determined by the strength of the patient’s immune response

Specific and effective cell mediated immunity (CMI) provides protection to a

person against leprosy. When specific CMI is effective in eliminating/ controlling
the infection in the body, lesions heal spontaneously or it produces pauci-bacillary
(PB) type of leprosy. If CMI is deficient; the disease spreads uncontrolled and
produces multi bacillary (MB) leprosy with multiple system involvement.
Sometimes, the immune response is abruptly altered, either following treatment
(MDT) or due to improvement of immunological status, which results in the
inflammation of skin or / and nerves and even others tissue, called as leprosy
reaction (types 1 and 2)

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 M.Leprae

M.Leprae entered into the body through respiration

Schwann cells in cooler places (Cutaneous nerves & peripheral

nerve trunks of limbs and face) Bacilli multiply in the Schwann
cells

Good CMI Response Weak CMI Response

1. No skin/nerve lesion appear, or 1. Multi bacillary / (MB) Leprosy

2. Skin/nerve lesions appear followed 2. In addition to skin and nerve, eyes,
by spontaneous healing , or testes, kidney, voluntary/smooth
muscles, reticulo endothelial
3. Pauci-bacillary (PB) Leprosy
system, and vascular endothelium
get involved

Disabilities and deformities

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 PATHOPHYSIOLOGY OF TUBERCULOSIS
DEFINITION:
TB is an airborne disease caused by the bacterium Mycobacterium tuberculosis
(M. tuberculosis). M. tuberculosis and seven very closely related mycobacterial
species (M. bovis, M. africanum, M. microti, M. caprae, M. pinnipedii, M. canetti
and M. mungi) together comprise what is known as the M. tuberculosis complex.
Most, but not all, of these species have been found to cause disease in humans.

Mycobacterium tuberculosis
MODE OF TRANSMISSION: M. tuberculosis is carried in airborne particles,
called droplet nuclei, of 1– 5 microns in diameter. Infectious droplet nuclei are
generated when persons who have pulmonary or laryngeal TB disease cough,
sneeze, shout, or sing. Depending on the environment, these tiny particles can
remain suspended in the air for several hours. M. tuberculosis is transmitted
through the air, not by surface contact. Transmission occurs when a person inhales
droplet nuclei containing M. tuberculosis, and the droplet nuclei traverse the mouth
or nasal passages, upper respiratory tract, and bronchi to reach the alveoli of the
lungs.

SYMPTOMS:

 Fever
  Night sweats
 Cough (often chronic)
 Hemoptysis (coughing up bloody sputum)
 Decrease or loss of appetite
 Weight loss and/or muscle loss (unintentional)
 Fatigue and/or malaise
 Chest pain (pain while breathing)
 Shortness of breath
 Swollen lymph nodes
 Pneumonitis (may be the only symptom in the elderly).

Other types are loosely classified as extra pulmonary and often have symptoms
that are nonspecific but frequently localized to the involved site. The following
includes the signs and symptoms of additional types of TB:

 Skeletal TB (also termed Pott's disease): spinal pain,

back stiffness, paralysis is possible
 TB meningitis: headaches (variable in length but persistent), mental
changes, coma
 TB arthritis: usually pain in a single joint (hips and knees most common)
 Genitourinary TB: dysuria, flank pain, increased frequency, masses or lumps
(granulomas)
 Gastrointestinal TB: difficulty swallowing, nonhealing ulcers, abdominal
pain, malabsorption, diarrhea (may be bloody)
 Miliary TB: many small nodules widespread in organs that resemble millet
seeds (hence its name)
 Pleural TB: empyema and pleural effusions
  Multidrug-resistant tuberculosis (MDR TB): patients infected with TB
bacteria that are resistant to multiple drugs
 XDR TB: patients infected with TB bacteria that are resistant to some of the
most effective anti-TB medications; XDR stands for extensively drug
resistant
 Caseous TB: Necrotic (dead and dying) tissue that is infected with TB
organisms has a soft, dry, and cheesy appearance.
 End-stage TB: Patients may suffer fever, constant coughing, shortness of
breath, weight loss, mental changes, and blood in their sputum before death.

TYPES AND SYMPTOMS:

Active TB

Active TB, sometimes called TB disease, causes symptoms and is contagious. The
symptoms of active TB vary depending on whether it’s pulmonary or
extrapulmonary.

 unexplained weight loss

 loss of appetite
 fever
 chills
 fatigue
 night sweats

Active TB can be life-threatening if not properly treated.

Latent TB
If you have latent TB infection, you have TB bacteria in your body, but it’s
inactive. This means you don’t experience any symptoms. You also aren’t
contagious. Still, you’ll have a positive result from TB blood and skin tests.

Latent TB can turn into active TB in 5 to 10 percentTrusted Source of people. This

risk is higher for those with a weakened immune system due to medication or an
underlying condition.

Pulmonary TB

Pulmonary TB is active TB that involves the lungs. It’s likely what most people
think of when they hear tuberculosis.

You contract it by breathing in air exhaled by someone who has TB. The germs
can remain in the air for several hours.

Along with the general symptoms of TB, a person with pulmonary TB may also
experience:

 persistent cough lasting three weeks or longer

 coughing up blood
 coughing up phlegm
 chest pain
 shortness of breath
Extrapulmonary TB: Extrapulmonary TB is TB that involves parts of the body

outside of the lungs, such as the bones or organs. Symptoms depend on the

part of the body affected.

TB lymphadenitis: TB lymphadenitis is the most common type of extrapulmonary

TB and involves the lymph nodes. It tends to affect the the cervical lymph nodes,
which are the lymph nodes in your neck. But any lymph node can be affected.
Swollen lymph nodes may be the only symptom you notice. But TB lymphadenitis
can also cause:

 fever
 fatigue
 unexplained weight loss
 night sweats

Skeletal TB: Skeletal TB, or bone TB, is TB that spreads to your bones from your
lungs or lymph nodes. It can affect any of your bones, including your spine and
joints.While skeletal TB is rare, it’s been on the rise in some countries with high
rates of HIV transmission and AIDS, which both weaken your immune
system.Initially, skeletal TB doesn’t cause symptoms. But over time, it can cause
general active TB symptoms in addition to:

 severe back pain

 stiffness
 swelling
 abscesses
 bone deformities
Miliary TB: Miliary TB is a form of TB that spreads in your the body, affecting
one or several organs. This type of TB often affects the lungs, bone marrow, and
liver. But it can also spread to other parts of the body, including the spinal cord,
brain, and heart. Military TB causes general active TB symptoms in addition to
other symptoms, depending on the body parts involved. For example, if your bone
marrow is affected, you may have a low red blood cell count or a rash.

Genitourinary TB: Genitourinary TB is the second most common typeTrusted

Source of extrapulmonary TB. It can affect any part of the genitals or urinary tract,
but the kidneys are the most common sites. It usually spreads to the area from the
lungs through the blood or lymph nodes.

Genitourinary TB can be spread through intercourse, though this is rareTrusted

Source. People with this type of TB often develop a tuberculous ulcer on the penis
or in the genital tract.

Other symptoms of genitourinary TB depend on the parts affected and may

include:

 testicular swelling
 painful urination
 decreased or interrupted flow of urine
 pelvic pain
 back pain
 decreased semen volume
 infertility

Liver TB: Liver TB is also called hepatic TB. It occurs when TB affects the liver.
It accounts for less than 1 percent of all TB infections. Liver TB can spread to the
liver from the lungs, gastrointestinal tract, lymph nodes, or the portal vein.
  high-grade fever
 upper abdominal pain
 liver enlargement
 jaundice

Gastrointestinal TB : Gastrointestinal TB is a TB infection that involves any part

of the gastrointestinal tract, which extends from the mouth to the anus. This type of
TB causes symptoms similar to other gastrointestinal conditions, such as Crohn’s
disease.

Symptoms of gastrointestinal TB depend on the area of the tract infected and may
include:

 abdominal pain
 loss of appetite
 weight loss
 change in bowel habits, such as diarrhea or constipation
 nausea
 vomiting
 an abdominal mass you can feel

TB meningitis: Also known as meningeal tuberculosis, TB meningitis spreads to

the meninges, which are the membranes surrounding the brain and spinal cord.

TB can spread to the meninges from the lungs or through the bloodstream. Unlike
other types of meningitis that develop quickly, TB meningitis usually develops
gradually.

It often causes vague symptoms in the beginning, including:

  aches and pains
 fatigue
 loss of appetite
 persistent headache
 low-grade fever
 nausea and vomiting

As the condition progresses, it can also bring on:

 severe headachess
 sensitivity to light
 neck stiffness

TB peritonitis: TB peritonitis is TB that causes inflammation of the peritoneum,

which is a layer of tissue that covers the inside of your abdomen and most of its
organs. It affects 3.5 percent Trusted Source of people with pulmonary TB and as
many as 58 percent Trusted Source of people with abdominal TB. Ascites and
fever are the most common symptoms of TB peritonitis. Ascites is a buildup of
fluid in the abdomen that causes abdominal swelling, bloating, and tenderness.

Other symptoms include:

 nausea
 vomiting
 loss of appetite

TB pericarditis: TB pericarditis occurs when TB spreads to the pericardium. This

consists of two thin layers of tissue separated by fluid that surround the heart and
hold it in place. It can present as different types of pericarditis,
including constrictive pericarditis, pericardial effusion, or effusive-constrictive
pericarditis.

Symptoms of TB pericarditis include:

 chest pain
 fever
 palpitations
 shortness of breath
 cough

Cutaneous TB: Cutaneous TB affects the skin. It’s very rare, even in countries
where TB is common. There are several different types of cutaneous TB, and it can
spread to other parts of the body.

The main symptoms of cutaneous TB are usually sores or lesions in different areas,
particularly the:

 elbows
 hands
 buttocks
 area behind the knees
 feet

These lesions may be:

 flat and painless

 purplish or brownish-red
 wart-like in appearance
  small bumps
 ulcers
 abscesses
RISK FACTORS:

 close contact with patients

 Visitors and immigrants from areas known to have high incidence of TB
 Children and the elderly with weakened immune systems (especially those
with a positive TB skin test, see below)
 Patients with HIV infection
 Drug abusers, especially IV drug abuse
 Head and neck cancer patients
 Transplant patients
 Diabetics
 Kidney disease patients
 People undergoing immunosuppressive therapy
 Silicosis

COMPLICATIONS:
Without treatment, tuberculosis can be fatal. Untreated active disease typically
affects lungs, but it can spread to other parts of your body through your
bloodstream. Examples of tuberculosis complications include:

 Spinal pain. Back pain and stiffness are common complications of

tuberculosis.
 Joint damage. Tuberculous arthritis usually affects the hips and knees.
 Swelling of the membranes that cover your brain (meningitis). This can
cause a lasting or intermittent headache that occurs for weeks. Mental changes
also are possible.
  Liver or kidney problems. Your liver and kidneys help filter waste and
impurities from your bloodstream. These functions become impaired if the
liver or kidneys are affected by tuberculosis.
 Heart disorders. Rarely, 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.

DIAGNOSIS:

Different tests are used to diagnose TB, but a healthcare provider will usually start
by checking for swollen lymph nodes and listening to someone’s breathing with a
stethoscope.

Next, they’ll likely do some additional testing to determine whether someone has
active or latent TB.

Mantoux tuberculin skin test (TST) : TST is performed by injecting a small

amount of tuberculin into the skin of the forearm. The skin will be monitored for a
reaction 48 to 72 hours after the injection. A positive skin test indicates that TB
bacteria is present, and additional tests are needed to determine if it’s active or
latent.

Blood tests: Blood tests can help to confirm or rule out active or latent TB. The
tests measure your immune system’s reaction to TB bacteria. There are two blood
tests. Trusted Source approved by the Food and Drug Administration for TB:

 T-SPOT TB test (T-Spot)

 QuantiFERON-TB Gold In-Tube test (QFT-GIT).

Imaging tests: Following a positive skin test, a healthcare provider may order
a chest X-ray or CT scan. These tests produce images that may show changes in
the lungs caused by active TB.

Sputum tests: Sputum is the mucus that comes up when you cough. Healthcare
providers sometimes collect sputum samples and test them for different strains of
TB bacteria, including antibiotic-resistant types.

PATHOGENESIS:

PATHOPHYSIOLOGY OF UTI
DEFINITION: A urinary tract infection (UTI) is an infection that affects part
of the urinary tract. When it affects the lower urinary tract it is known as
a bladder infection (cystitis) and when it affects the upper urinary tract it is
known as a kidney infection(pyelonephritis).

UTIs can be categorized depending on the location of infection (e.g. upper or

lower)

Upper UTI: infection of the kidney (pyelonephritis). Significant bacteriuria is

defined as > 105colony forming units (CFU)/ml. In the absence of symptom

Lower UTI: infection of the bladder (cystitis).

Uncomplicated UTI: if occurring in healthy non-pregnant adult women.

Complicated UTI: the presence of factors that increase the risk of treatment
failure (e.g diabetes, structural abnormalities, catheter

UTIs occurring in men are generally considered ‘complicated’ as the vast majority
occur in children and the elderly in association with urological abnormalities.

Aetiology: UTIs are caused by the organism Escherichia coli in 75-90% of cases.
Escherichia coli (E. coli) is a gram-negative bacillus that is a facultative inhabitant
of the large intestines. E. coli may cause a wide range of infections including,
respiratory infections, intra-abdominal infections, enteric infections and urinary
infections.

Uropathogenic strains of E. coli infect the urinary tract leading to a wide range of
problems including urethritis, prostatitis, cystitis, pyelonephritis and urosepsis.

Other common microorganisms associated with UTIs include:

 Proteus mirabilis
 Klebsiella pneumoniae
 Staphylococcus saprophyticus

Pathophysiology: The normal urinary tract is a sterile environment. The

development of UTIs results from colonization and ascending spread of
microorganisms from the urethra into the bladder (lower) and kidney (upper), or by
haematogenous spread via the blood. Many pathogens have adoptions that allow
them to breach host defenses.

E. coli is the most common bacteria causing acute pyelonephritis due to its unique
ability to adhere to and colonize the urinary tract and kidneys. E.coli has adhesive
molecules called P-fimbriae which interact with receptors on the surface of
uroepithelial cells. Kidneys infected with E. coli can lead to an acute inflammatory
response which can cause scarring of the renal parenchyma. Though the
mechanism in which renal scarring occurs is still poorly understood, it has been
hypothesized that the adhesion of bacteria to the renal cells disrupts the protective
barriers, which lead to localized infection, hypoxia, ischemia, and clotting in an
attempt to contain the infection. Inflammatory cytokines, bacterial toxins, and
other reactive processes further lead to complete pyelonephritis and in many cases
systemic symptoms of sepsis and shock.
Microorganism spread
In women, infections start with the colonisation of the vaginal introitus (entrance to
the vaginal canal) and periurethral area.

It then ascends the urethra to cause infection of the bladder.

Infections are uncommon in men for a number of reasons.

They have a longer urethra, prostatic secretions have some antimicrobial properties
and their periurethral area is generally drier.

UTIs may also develop from the haematogenous spread of microorganisms.

However, common gram-negative bacilli (e.g. E. coli) are unlikely to cause
infection by this route. Haematogenous spread is more often seen with uncommon
urinary microorganisms such as Staphylococcus
aureus, Candida albicans and Mycobacterium tuberculosis.

Host and pathogen

The ability of microorganisms to infect the urinary system is dependent on both the
host and pathogen. Host factors such as intercurrent illness, immunosuppression
(e.g. steroid use) or co-morbidities (e.g. diabetes) can increase the risk of
developing a UTI.

Some pathogens are particularly well suited to infecting the urinary tract.

For example, uropathogenic strains of E. coli contain fimbriae, these are hair-like
protein polymers that project from the bacterial surface. They allow strong
adherence to the urothelium. Fimbriae play a crucial role in the pathogenesis of
UTIs and have been shown to increase bacterial survival.

Risk factors

UTIs are extremely common especially among young, sexually active females.
Risk factors for the development of UTIs include:

 Recent sexual intercourse

 Diabetes
 History of UTIs
 Spermicide use
  Catheters

Urinary catheters are one of the major risk factors for developing a UTI in
secondary care. UTIs associated with catheters are a leading cause of hospital-
associated bacteraemia.

Clinical features

Typical clinical features of UTIs may be subtle in the young and elderly

Symptoms Signs

 Flank pain  Dysuria

 Confusion  Urine frequency
 Costovertebral  Urgency
angle tenderness  Incontinence
 Urosepsis Fever  Suprapubic pain

Rigors Haematuria

Urosepsis refers to a sepsis that originates from a urinary infection. It should be

suspected in patients where the likely source of infection is urinary and parameters
consistent with systemic inflammatory response syndrome (SIRS). SIRS is
diagnosed if 2 or more of the following criteria are met:

 Temperature: > 38°, < 36°

 Heart rate: > 90 bpm
 Respiratory rate: > 20 breaths/min
 WCC: > 12,000 cell/min3, < 4000 cell/min3
Diagnosis & investigations
The definitive diagnosis of a UTI is based on typical clinical features associated
with positive laboratory evidence of pyuria +/- bacteriuria.
Urinalysis, involving a urine dipstick and urinary microscopy, culture &
sensitivity, (MC&S), is key.

Urine dipstick

Urinary MC&S

X-Ray

PATHOPHYSIOLOGY OF AIDS
HIV
HIV AIDS is a spectrum of conditions caused by infection with the human immunodeficiency
virus. Human immunodeficiency virus infection for infants, children and adoloscents is
represented by a continuum of immunologic and clinical classifications ranging from no to
severe immunologic suppression and asymptomatic to severely symptomatic.
IMMUNOGLOBULINS
IgG : major serum immunoglobulin
only maternal immunoglobulin that is normally transported across the placenta and provides
natural passive immunity in the newborn. Neutralises the viruses, encourage phagocytosis.
IgA : main immunoglobulin in the colostrum, saliva and tears.
IgM : earliest immunoglobulin to be synthesised by the foetus (beginning by about 20 weeks
of age). It is not transported across placenta
its presence in foetus or newborn indicates intrauterine infection & its detection is useful in
thediagnosis of congenital infections such as syphilis, HIV rubella, toxoplasmosis.
IgD : # accounts for 0.2% of serum antibodies.
IgD & IgM occur on the surface of unstimulated B lymphocytes and serves as recognition
receptors for antigens. IgE : # responsible for anaphylactic type of hypersensitivity.
protection against pathogens by mast cell degranulation and release of inflammatory mediators.
ETIOLOGY: Caused by HUMAN IMMUNODEFICIENCY VIRUS
MODES OF TRANSMISSION HIV is transmitted primarily via :-
 Unprotected sexual intercourse
 Contaminated blood transfusion
 Hypodermic needles
 Mother to child during pregnancy, delivery and breastfeeding

PATHOGENESIS :
1. HIV virus enters in the blood of foetus through the placenta of infected mother OR
through any other mode of transmission
2. Than the virus comes in contact with CD4 lymphocytes
 3. It binds with CD4 antigen present on the T lymphocytes and B lymphocytes
4. After binding the virus enters the cells
5. Inside the cell, the virus genome uncoats and with the help of reverse transcriptase,
converts the single RNA into double stranded DNA
6. This DNA integrates into the infected cell genome
7. This integration causes the formation of HIV virus progeny with the help of host
cell

SOME GENERAL FEATURES

 Generalised lymphoadenopathy, especially in axillary areas.
 Persistent or recurrent oral candidiasis
 Developmental delays
 Hepatomegaly,
 Spleenomegaly
 Persistent diarrhea
 Unexplained anaemia
 Thrombocytopenia
 Unexplained cardiac and kidney disease

CLINICAL STAGING: ACCORDING TO WHO, there is a clinical staging for HIV infection
and related diseases in children.
STAGE 1
•Asymptomatic PAPULAR PRURITIC ERUPTIONS
•Persistent generalised lymphoadenopathy
STAGE 2
•Papular pruritic eruptions
•Fungal nail infection
• Angular cheilitis
• Lineal gingival erythema
• Recurrent oral ulceration
• Recurrent chronic URTI
STAGE 3
• Unexplained moderate malnutrition
• Unexplained persistent diarrhea (14 days or more)
• Unexplained persistent fever ( above 37.5°C intermittent or constant, for longer than 1 month).
STAGE 4
• Unexplained severe wasting, severe malnutrition not responding to standard therapy.
• Pneumocystis pneumonia
• Recurrent severe bacterial infections
• Chronic herpes simplex infection
• Esophageal candidiasis
• Kaposi’s sarcoma
DIAGNOSIS:
ELISA, PCR, WESTERN BLOR, CBC
COMPLICATIONS:
Recurrent Viral and Bacterial infections
Opportunistic infections (TB, PCP, Syphilis, Gonorrhoea, Candidiasis

PATHOPHYSIOLOGY OF SYPHILIS
Syphilis is caused by gram –ve bacteria.

Causative organism : Treponema pallidum

Incubation period: 21 days

Mode of transmission:

Unsafe sex

Vertical transmission from mother to baby(congenital syphilis)

Types of Syphilis:

Primary syphilis (appearance of 1 Chancre)

2-3 months

Secondary syphilis (highly infectious with multiple chancres which are painless)

2-3 years

Tertiary or Neuro syphilis (highly dangerous)

Syphilis is a bacterial infection usually spread by sexual contact. The disease starts as a painless
sore called “Chancre” - Typically on your genitals, rectum or mouth. Syphilis spreads from
person to person via skin or mucous membrane contact with these sores .After the initial
infection, the syphilis bacteria can lie dormant in your body for decades before becoming active
again.

Primary syphilis

Syphilis develops in stages, and symptoms vary with each stage. But the stages may overlap, and
symptoms don't always occur in the same order. You may be infected with syphilis and not
notice any symptoms for years.. The chancre usually develops about three weeks after exposure.
Many people who have syphilis don't notice the chancre because it's usually painless, and it may
be hidden within the vagina or rectum. The chancre will heal on its own within three to six
weeks.

Secondary syphilis

Within a few weeks of the original chancre healing, you may experience a rash that begins on
your trunk but eventually covers your entire body — even the palms of your hands and the soles
of your feet. This rash is usually not itchy and may be accompanied by wart-like sores in the
mouth or genital area. Some people also experience hair loss, muscle aches, a fever, sore throat
and swollen lymph nodes. These signs and symptoms may disappear within a few weeks or
repeatedly come and go for as long as a year.

Latent syphilis

If you aren't treated for syphilis, the disease moves from the secondary to the latent (hidden)
stage, when you have no symptoms. The latent stage can last for years. Signs and symptoms may
never return, or the disease may progress to the tertiary (third) stage.

Tertiary (late) syphilis

About 15 to 30 percent of people infected with syphilis who don't get treatment will develop
complications known as tertiary (late) syphilis. In the late stages, the disease may damage your
brain, nerves, eyes, heart, blood vessels, liver, bones and joints. These problems may occur many
years after the original, untreated infection.

Congenital syphilis
Babies born to women who have syphilis can become infected through the placenta or during
birth. Most newborns with congenital syphilis have no symptoms, although some experience a
rash on the palms of their hands and the soles of their feet. Later symptoms may include
deafness, teeth deformities and saddle nose — where the bridge of the nose collapses.

Causes

The cause of syphilis is a bacterium called Treponema pallidum. The most common route of
transmission is through contact with an infected person's sore during sexual activity. The bacteria
enter your body through minor cuts or abrasions in your skin or mucous membranes. Syphilis is
contagious during its primary and secondary stages, and sometimes in the early latent period.

Less commonly, syphilis may spread through direct unprotected close contact with an active
lesion (such as during kissing) or through an infected mother to her baby during pregnancy or
childbirth (congenital syphilis).

Risk factors:

 Engage in unprotected sex  Male with male intercourse

 Sex with multiple partners  Immune suppression(HIV)

Gummas usually disappear after treatment with antibiotics.

Neurological problems

Syphilis can cause a number of problems with your nervous system, including:

 Stroke  Sexual dysfunction in men

(impotence)
 Meningitis
 Bladder incontinence
 Hearing loss
 Sudden, lightning-like pains
 Visual problems
 Dementia
 Loss of pain and temperature
sensations
Cardiovascular problems

These may include bulging (aneurysm) and inflammation of the aorta — your body's major
artery — and of other blood vessels. Syphilis may also damage heart valves.

HIV infection

Adults with sexually transmitted syphilis or other genital ulcers have an estimated two- to
fivefold increased risk of contracting HIV. A syphilis sore can bleed easily, providing an easy
way for HIV to enter your bloodstream during sexual activity.

Pregnancy and childbirth complications

Congenital syphilis greatly increases the risk of miscarriage, stillbirth or your newborn's death
within a few days after birth.