ETIOLOGY & PATHOPHYSIOLOGY - PowerPoint Presentation

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ETIOLOGY & PATHOPHYSIOLOGY

OF Pyrexia of Unknown Origin (PUO) & Pneumonia

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Pyrexia of Unknown Origin (PUO)

Definition

Petersdorf and Beeson defined pyrexia of unknown origin (PUO) in 1961. It is defined as:

A temperature greater than 38.3°C on several occasions.

This should be accompanied by more than 3 weeks of illness.

There should also be failure to reach a diagnosis, after 1 week of inpatient investigation.

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Pathophysiology

Fever is a

natural response

of the body that helps in fighting off foreign substances, such as microorganisms, toxins, etc.

Body temperature is set by the thermoregulatory center, located in an area in the brain called hypothalamus.

cytokines cause the thermoregulatory

center in the hypothalamus to reset the normal temperature level.

The body's initial response is to conserve heat by

vasoconstriction,

a process in which blood vessels narrow and prevent heat loss from the skin and elsewhere. This alone will raise temperature by two to three degrees.

Fever is a body defense mechanism. It has been shown that one of the effects of temperature

increase is to slow

bacterial growth.

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Common causes of PUO

Most cases are unusual presentations of common diseases e.g. tuberculosis, endocarditis, gallbladder disease and HIV infection, rather than rare or exotic diseases.

In adults: infections and cancer (25-40% of cases each) account for most of PUOs.

Children: 30-50% of cases are due to infections, 5-10% cancer, autoimmune disorders 10-20%.

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Bacterial

Abscesses

There may be no localising symptoms.

Previous abdominal or pelvic surgery, trauma .

Most commonly in the

subphrenic

space, liver, right lower quadrant, retroperitoneal space or the pelvis in women.

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Tuberculosis (TB)

caused by

Mycobacterium tuberculosis

in humans. Most infections in humans result in an asymptomatic.

The classic symptoms are a chronic cough with blood-tinged sputum, fever, night sweats, and weight loss. Infection of other organs .

More people in the developed world are contracting tuberculosis because their immune systems are compromised by immunosuppressive drugs, substance abuse, or AIDS.

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Urinary tract infections

(UTIs) are rare causes.

Perinephric

abscesses occasionally fail to communicate with the urinary system resulting in a normal urinalysis

Hepatobiliary

infections

e.g.

cholangitis

can occur without local signs and with only mildly elevated or normal liver function tests especially in the elderly.

Osteomyelitis

Subacute

in onset, there is dull, constant pain and soft tissue swelling/tenderness over the involved bone, with low-grade fever.

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Brucellosis

should be considered in patients with persistent fever and a history of contact with cattle, swine, goats or sheep, or patients who consume raw milk products.

Giant cell arthritis

Consider when an elderly patient develops a new headache associated with a tender, ropy, or nodular temporal artery and/or fever.

Other spirochetal diseases that can cause PUO include

Spirillum minor

(

Rat-bite fever

),

Borrelia

burgdorferi

(

Lyme disease

), and

Treponema

pallidum

(

syphilis

).

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Viral

Herpes viruses such as

cytomegalovirus

and

Epstein-Barr virus

(EBV) can cause prolonged febrile illnesses with constitutional symptoms and no prominent organ manifestations, particularly in the elderly.

HIV:

Prolonged febrile episodes are frequent in patients with advanced HIV infection.

Suspect tuberculosis in high-risk patients such as HIV-infected persons, tuberculosis is usually extra pulmonary (bones, nodes, renal, genitals, or liver).

Over 80% of patients with

AIDS

and lymphomas have involvement of extranodal sites - usually the brain.

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Fungi

Immunosuppression

, the use of broad-spectrum antibiotics, the presence of intravascular devices and total

parenteral

nutrition all predispose people to disseminated fungal infections.

Parasites

Toxoplasmosis

: This should be considered in patients who are febrile with lymph node enlargement.

Trypanosoma

,

leishmania

and amoeba species may rarely cause PUO.

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Rickettsial

organisms

Coxiella

burnetii

may cause chronic infections, chronic Q fever or Q fever endocarditis may be identified in patients with a PUO.

Psittacosis

Infection by the causative organism,

Chlamydophila

should be considered in a patient with PUO who has a history of contact with birds.

Lymphogranuloma

venereum

This should also be considered

, but is rare.

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Drug fever

The most common are beta-

lactam

antibiotics, procainamide (now discontinued) and isoniazid. Stopping the drug generally leads to recovery within 2 days.

may be due to serum sickness, allergy, or immune-mediated vasculitis.

It is usually accompanied by a rash.

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Collagen vascular and autoimmune diseases

Systemic-onset

juvenile rheumatoid arthritis

. High-spiking fevers, non-

pruritic

rashes,

arthralgias

and

myalgias

,

pharyngitis

and

lymphadenopathy

typically are present.

Polyarteritis

nodosa

(PAN), rheumatoid arthritis and mixed connective-tissue diseases should be considered.

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Neoplasms

Hodgkin and non-Hodgkin lymphomas may cause PUO.

Leukaemias may also be responsible.

Among solid tumours, renal cell carcinoma is most commonly associated with PUO.

Vasculitides

Giant cell

arteritis

and also the related polymyalgia rheumatica

Polyarteritis nodosa

Behcet's has also been reported

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Inherited diseases

Familial

mediterranean

fever

  a hereditary disease usually seen in Armenians and Sephardic Jews, with short recurrent attacks of fever, pain in the abdomen, chest, or joints, and

erythema

like that of erysipelas; it may be complicated by

amyloidosis

.

Hyperthyroidism and

subacute

thyroiditis

These are the most common endocrine causes of PUO.

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Diagnosis

when a fever over 101°F (38.5°C) remains unexplained for longer than 3 weeks, is usually a result of infection (40%), neoplasm (20%), or collagen-vascular disease (20%).

Record all complaints even if not currently present.

Discuss nutrition including consumption of products and source of these products.

Drug history should be recorded, to include over-the-counter medications,

Immunization status should be documented.

Enquire about family history of illness.

Occupational history should include illicit substances.

Sexual history should be recorded.

Take a history of travel and recreational habits

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Examine for subtle clues &

Clinical Findings

Extreme elevations of fever

(40°C )

it is found in heat stroke,

hypothalamic dysfunction,

meningitis,

midbrain hemorrhage,

falciparum

malaria.

Relative bradycardia occurs

typhoid fever,

meningitis with increased ICT,

factitious fever, tularemia,

brucellosis, mumps,

hepatitis, and

with concomitant beta blockers.

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Relapsing fever

(days of fever alternating with days without) occur in

brucellosis (fever with physical activity),

Hodgkin's disease,

extrapulmonary

tuberculosis,

malaria, and Lyme disease.

Hectic fever.

FUO lasts longer than 6 months

,

consider factitious fever,

granulomatous

hepatitis,

neoplasm, Still disease,

infection,

collagen-vascular disease.

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Jwara samprapti

Jirna Jwara च. चि. ३ त्रिसप्ताहे व्यतीते तु ज्वरो यस्तनुताम् गताः। प्लिहोग्निसादम् कुरुते स जीर्णोज्वरमुच्यते।मा.नि. मधुकोष

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त्रिसप्ताहे Fever continuous after 21 days ,indicating chronicity & long duration of fever may be due to failure in diagnosis or in treatment.मन्दज्वरा : it may be due to failure of immune system to control infections.प्लिहावृद्धी: Angnimandya lead to disturbance in Dhatupotion Dhatukshaya Vataprakopa Medakshaya Pliharuddhi.

च. चि. ३

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Pneumonia

Definition

Pneumonia

is an abnormal inflammatory condition of the lung. it is often characterized as including inflammation of the parenchyma of the lung (that is, the alveoli)

and

abnormal alveolar filling with fluid (consolidation and exudation).

Classification

Early classification schemes

Initial descriptions of pneumonia focused on the

anatomic

or

pathologic

appearance of the lung, either by direct inspection at autopsy or by its appearance under a microscope.

Lobar pneumonia

Interstitial pneumonia

Bronchial pneumonia

Multilobar

pneumonia

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Combined clinical classification

Traditionally, clinicians have classified pneumonia by clinical characteristics, dividing them into "acute" (less than

three weeks

duration) and "chronic" pneumonias.

Chronic pneumonias

, on the other hand, mainly include those of

Nocardia

,

Actinomyces

and

Blastomyces

as well as the granulomatous pneumonias (

Mycobacterium tuberculosis

and atypical mycobacteria,

Histoplasma

capsulatum

.

Acute pneumonias

are further divided into the classic bacterial

broncho

pneumonia's (such as

Streptococcus pneumoniae

),

The atypical pneumonias (such as the

interstitia

l pneumonitis of

Mycoplasma pneumoniae

), and the aspiration pneumonia syndromes.

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* There are two broad categories of pneumonia

;

1) Community-acquired pneumonia (CAP) 2)Hospital-acquired pneumonia. A recently introduced type of

healthcare-associated pneumonia

lies between these two categories.

1)

Community-acquired pneumonia (CAP

):it is infectious pneumonia in a person who has not recently been hospitalized. CAP is the most common type of pneumonia.

Streptococcus pneumoniae

is the most common cause of CAP The term "walking pneumonia" has been used to describe a type of community-acquired pneumonia of less severity usually caused by the atypical bacterium,

Mycoplasma

pneumoniae

.

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2)Hospital-acquired pneumonia

, also called

Nosocomial

pneumonia, is pneumonia acquired during or after hospitalization for another illness or procedure with onset at least 72 hrs after admission. Hospital-acquired microorganisms may include resistant bacteria such as

MRSA

,

Pseudomonas

,

Enterobacter

, and

Serratia

.

Ventilator-associated pneumonia

(VAP) is a subset of HAP, VAP is pneumonia which occurs after at least 48 hours of

intubation

and

mechanical ventilation

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Other types of pneumonia

1)

Severe acute respiratory syndrome(SARS) .

2)

Bronchiolitis

obliterans

organizing pneumonia(BOOP) .

3)

Eosinophilic

pneumonia.

4)Chemical pneumonia.

5)Aspiration pneumonia.

6)Dust pneumonia.

7)Necrotizing pneumonia,

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Signs and symptoms

People with infectious pneumonia often have

1) cough producing greenish or yellow sputum or phlegm. 2)High fever that may be accompanied by shaking chills. 3)Shortness of breath is also common.

4) A pleuritic chest pain, a sharp or stabbing pain, either experienced during deep breaths or coughs or worsened by them.

5) People with pneumonia may cough up blood.

6)experience headaches, or develop sweaty and clammy skin.

pneumonia caused by

Legionella

may cause abdominal pain and

diarrhea

, while pneumonia caused by

tuberculosis

or

Pneumocystis

may cause only weight loss and night sweats.

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Cause

The symptoms of infectious pneumonia are caused by the invasion of the lungs by microorganisms and by the immune system's response to the infection The most common causes of pneumonia are

viruses

and

bacteria

Viruses

A virus reaches the lungs when airborne droplets are inhaled through the mouth and nose. virus directly kills the cells. When the immune system responds to the viral infection, even more lung damage occurs lymphocytes, activate certain chemical cytokines which allow fluid to leak into the alveoli. This combination of cell destruction and fluid-filled alveoli.

Viral pneumonia is commonly caused by viruses such as

influenza virus

,

respiratory

syncytial

virus

(RSV),

adenovirus

, and

metapneumovirus

.

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Bacteria. Streptococcus pneumoniae, often called "pneumococcus", is the most common bacterial cause of pneumonia . Bacteria enter the lung when airborne droplets are inhaled, but can also reach the lung through the bloodstream through infection in another part of the body. 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 . fluid from surrounding blood vessels fill the alveoli and interrupt normal oxygen transportation. Less common causes of infectious pneumonia are fungi, parasites & Idiopathic interstitial pneumonias (IIP) are a class of diffuse lung diseases

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Pneumonia as seen on chest x-ray. A: Normal chest x-ray. B: Abnormal chest x-ray with shadowing from pneumonia in the right lung (white area, left side of image).

Investigations

An important test for pneumonia in unclear situations is a chest x-ray. Chest x-rays can reveal areas of opacity (seen as white) which represent consolidation.

chest CT (computed tomography

)

can reveal pneumonia that is not seen on chest x-ray. X-rays can be misleading, because other problems, like lung scarring and congestive heart failure

Sputum cultures take at least two to three days.

Heamogram ,RFT,LFT, ect.

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Differential diagnosis

. Chronic obstructive pulmonary disease (COPD) or asthma can present with a polyphonic wheeze, similar to that of pneumonia. Other diseases to be taken into consideration include bronchiectasis, lung cancer and pulmonary emboli.ComplicationsRespiratory and circulatory failure ,Pneumonia can also cause respiratory failure by triggering acute respiratory distress syndrome (ARDS). Pleural effusion. Chest x-ray showing a pleural effusion. The A arrow indicates "fluid layering" in the right chest. empyema, and abscess

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Normal AP CXR.

Normal lateral CXR.

AP CXR showing left lower lobe pneumonia associated with a small left sided pleural effusion.

AP CXR showing right lower lobe pneumonia.

A lateral CXR showing right lower lobe pneumonia

1 2 3 4

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श्वसनको ज्वर

(

pneumonia )

लाक्षरसाभं य ष्ठीवेत् रक्तं श्वासज्वरार्दितः।

स्त्यानफुप्फुसमूलस्य तस्य श्वसनको ज्वरः।सि. नि .

कर्कटक ज्वर

(pneumonia )

मध्यहीन प्रवृद्धैस्तु वातपित्तकफच्य याः।

अन्तर्दाहो विशेषोऽत्रो न च वक्तुं स शक्यते।

रक्त्मालक्तकेनैव लक्ष्यते मुखमण्डलम्।

पित्तेनाकर्षितः श्लेष्मा हृदयान्न प्रसिच्यते।

इषुणेतेवाहतं पार्श्व तुद्यते खन्यते हृदि।

प्रमिलकश्वासहिक्का वर्धते तु दिने दिने।

.....कूजेच्चापि कपोतवत्।

अतीव श्लेष्माणां पूर्णः शुष्कवक्त्रौष्ठतालुकः।

आयम्यते च बहुशो रक्तं ष्ठीवति चाल्पशः।

एष कर्कटको नाम्ना सन्निपातः सुदारुणः

।

भा. पु.

ज्वरचिकित्सा

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