Transcript DISEASES OF THE RESPIRATPORY SYSTEM LECTURE 1

DISEASES OF THE RESPIRATPORY SYSTEM
PHARMACOLOGY
LECTURE 1/2
DR HEYAM AWAD
FRCPATH
STRUCTURE OF THE RESPIRATORY SYSTEM
STRUCTURE OF THE RESPIRATORY SYSTEM
ALVEOLI
ALVEOLI: LARGE SURFACE AREA
ALVEOLI: RICH BLOOD SUPPLY
ALVEOLI: THIN MEMBRANES
ATELECTASIS = LUNG COLLAPSE
TYPES OF ATELECTASIS
RESORPTION ATELECTASIS
• OBSTRUCTION BY:
*MUCOUS OR MUCOPURULENT PLUG
(POST-OP, ASTHMA, BRONCHIECTASIS OR
CHRONIC BRONCHITIS)
*TUMOUR.
*FOEIGN BODY .
COMPRESSION ATELECTASIS
ACCUMOLATION OF :
• FLUID (PLEURAL EFFUSION)
• BLOOD (HAEMOTHORAX)
• AIR (PNEUMOTHORAX)
ALL WITHIN THE PLEURAL CAVITY.
CONTRACTION ATELECTASIS
• LOCAL OR GENERALISED FIBROSIS.
• ATELECTASIS…………….IS IT REVERSIBLE???????
ADULT RESPIRATORY DISTRESS
SYNDROME
ACUTE LUNG INJURY
•
•
•
•
BILATERAL PULMONARY DAMAGE.
ENDOTHELIAL AND EPITHELIAL DAMAGE.
DUE TO DIRECT OR INDIRECT LUNG INJURY.
ACUTE DYSPNEA + HYPOXEMIA + BILATERAL
PULMONARY INFILTRATES WITHOUT PRIMARY
LEFT SIDED HEART FAILURE.
• CAN PROGRESS TO ACUTE RESPIRATORY
DISTRESS SYNDROME.
MAIN CAUSES OF ACUTE LUNG INJURY
DIRECT LUNG DAMAGE :
• PNEUMONIA.
• ASPIRATION.
INDIRECT LUNG INJURY :
• SEPSIS.
• SEVERE TRAUMA WITH SHOCK.
ACUTE RESPIRATORY DISTRESS
SYNDROME: CLINICAL FEATUERES.
• LIFE THREATENING RESPIRATORY
INSUFFICIENCY.
• CYANOSIS.
• HYPOXEMIA REFRACTORY TO OXYGEN
THERAPY.
• MAY PROGRESS TO MULTISYSTEM ORGAN
FAILURE.
CLINICAL FEATURES
• 80% DEVELOP ARDS WITHIN 72 HOURS OF
THE INSULT.
• MORTALITY DECREASED FROM 60% TO 40% IN
USA IN THE LAST DECADE.
• POOR PROGNOSIS:
*OLD AGE.
*SEPSIS.
*MULTISYSTEM FAILURE.
OUTCOME
• SURVIVORS END WITH DIFFUSE INTERSTITIAL
FIBROSIS.
• THIS CAUSES COMPROMISE OF RESPIRATORY
FUNCTION.
• SURVIVALS WHO DON’T HAVE CHRONIC
CONSEQUENCES RETAIN NORMAL
RESPIRATORY FUNCTION WITHIN 6-12
MONTHS.
OBSTRUCTIVE VS RESTRICTIVE LUNG
DISEASES
• OBSTRUCTIVE: LIMITATION OF AIRFLOW.
• RESTRICTIVE: REDUCED EXPANSION, AND
DECRESED TOTAL CAPACITY.
OBSTRUCTIVE LUNG DISEASES
• COPD: EMPHYSEMA AND CHRONIC
BRONCHITIS.
• ASTHMA.
• BRONCHIECTASIS.
COPD
EMPHYSEMA
• ABNORMAL, PERMANENT ENLARGEMENT OF
AIR SPACES DISTAL TO TERMINAL
BRONCHIOLES ALONG WITH DESTRUCTION TO
THEIR WALLS WITHOUT SIGNIFICANT
FIBROSIS.
TYPES OF EMPHYSEMA
CENTRIACINAR = CENTRILOBULAR
• MORE SEVERE IN THE UPPER LOBES OF
LUNGS.
• SMOKING ASSOCIATED.
PANACINAR EMPHYSEMAM
• MOSTLY AFFECTS LOWER LUNG ZONES.
• ASSOCIATED WITH ALPHA 1 ANTITRYPSIN
DIFICIENCY.
MORPHOLOGY
HISTOPATHOLOGY
CLINICAL FEATURES
•
•
•
•
•
DYSPNEA .
WEIGHT LOSS.
PROLONGED EXPIRATION.
BLOOD GASES RELATIVELY NORMAL.
PINK PUFFERS
Pink puffers
CHRONIC BRONCHITIS
PERSISTENT PRODUCTIVE COUGH FOR AT LEAST
THREE CONSECUTIVE MONTHS FOR AT LEAST
TWO CONSECUTIVE YEARS.
CHRONIC BRONCHITIS
CAUSES
• SMOKING RELATED.
• AIR POLLUTION.. SO2, NO.
PATHOGENESIS
• HYPERSECRETION OF MUCUS.
• DUE TO HYPERTROPHY OF MUCUS SECRETING
GLANDS IN TRACHEA AND MAIN BRONCHI.
• INCREASE IN MUCIN SECRETING GOBLET
CELLS IN THE EPITHELIUM OF SMALL
BRONCHIA.
CLINICAL FEATURES
•
•
•
•
PRODUCTIVE COUGH.
HYPERCAPNIA.
HYPOXEMIA.
CYANOSIS.
• BLUE BLOATERS
ASTHMA
• CHRONIC INFLAMMATORY DISORDER WHICH
CAUSES RECURRENT EPISODES OF WHEEZING,
BREATHLESSNESS, COUGH, AND CHEST
TIGHTNESS.
ASTHMA
INTERMITTENT, REVERSIBLE :
• AIRWAY OBSTRUCTION.
• CHRONIC BRONCHIAL INFLAMMATION WITH
EOSINOPHILS.
• BRONCHIAL SMOOTH MUSCLE HYPERTROPHY
AND HYPERREACTIVITY.
• INCREASED MUCUS SECRETION.
TYPES OF ASTHMA
• ATOPIC: EVIDENCE OF ALLERGIC
SENSITIZATION.
• NONATOPIC.
TYPES OF ASTHMA
•
•
•
•
•
•
ATOPIC :
THE MOST COMMON TYPE.
BEGINS IN CHILDHOOD.
TYPE 1 HYPERSENSITIVITY REACTION.
POSITIVE FAMILY HISTORY.
TRIGGERED BY ENVIRONMENTAL ANTIGENS
OR INFECTIONS.
NON ATOPIC ASTHMA
•
•
•
•
•
NO EVIDENCE OF ALLERGEN SENSITIZATION
SKIN TEST NEGATIVE.
POSITIVE FAMILY HISTORY IS LESS COMMON.
INFECTIONS COMMON.
VIRAL INFLAMMATION LOWERS THRESHOLD OF
THE SUBEPITHELIAL VAGAL RECEPTORS TO
IRRITANTS.
• HUMORAL AND CELLULAR MEDIATORS SIMILAR
TO ATOPIC ASTHMA.
DRUG INDUCED ASTHMA
• ASPIRIN
• MECHANISM UNKNOWN
• ASPIRIN INHIBITS COX WITHOUT AFFECTING
LIPOOXYGENASE PATHWAY SHIFTING THE
BALANCE TO BRONCHOSPASM.
OCCUPATIONASL ASTHMA
• PLASTIC FUMES.
• ORGANIC AND CHEMICAL DUST E.G WOOD,
COTTON.
• GASES: TOLUENE
CLINICAL FEATURES
• SEVERE DYDPNEA AND WHEEZING.
• LABOUR TO INSPIRE AND CAN NOT EXPIRE.
THIS RESULTSIN HYPERINFLATION.
• ATTACKS LAST FOR 1 TO SEVERAL HOURS.
SARCOIDOSIS
• MULTISYSTEM DISEASE OF UNKNOWN
ETIOLOGY.
• NONCASEATING GRANULOMAS IN MULTIPLE
ORGANS.
• DIAGNOSIS: BY EXCLUSION.
• NONCASEATING GRANULOMAS:
*MYCOBACTERIA.
*FUNGAL INFECTIONS.
*BERYLLIOSIS.
• MAJOR PRESENTATION OF SARCOIDOSIS:
BILATERAL HILAR LYMPHADENOPATHY
AND/OR LUNG INVOLVEMENT.
• EYE AND SKIN INVOLVEMENT EACH OCCUR IN
25% OF CASES.
EPIDEMIOLOGY
• ADULTS < 40.
• HIGHER PREVALENCE AMONG NONSMOKERS.
OUTCOME
• UNPREDICTABLE COURSE.
• EITHER PROGRESSIVE CHRONICITY OR
RELAPSES AND REMISSIONS.
• REMISSIONS ARE EITHER SPONTANEOUS OR
WITH STEROIDS.
SARCOID GRANULOMAS
TUBERCULOSIS
• INFECTIOUS DISEASE CAUSED BY
MYCOBACTERIUM TUBERCULOSIS.
• CAUSES CASEATING GRANULOMAS.
• MAINLY AFFECTS LUNGS, BUT OTHER ORGANS
CAN BE AFFECTED.
EPIDEMIOLOGY
• A LEADING CAUSE OF DEATH IN DEPRIVED
COUNTRIES.
• WESTERN WORLD : DEATH DUE TO TB
DECLINED IN THE 19TH CENTURAY .
• RESURGENCE OF CASES SINCE 1984 DUE TO
HIV INFECTION.
• MORE PREVALENT IN IMMEGRANTS IN USA.
TRANSMISSION
ETIOLOGY
• MYCOBACTERIA TUBERCULOSIS
HISTOLOGY
SYSTEMIC MILIARY TB
• BACILLI DISSIMINATE THRGH SYSTEMIC
CIRCULATION.
• CAN AFFECT ANY ORGAN.
• MAINLY: LIVER, BONE MARROW, SPLEEN,
ADRENALS, MENINGES, KIDNEYS, F.TUBES AND
EPIDIDYMIS.
PROGNOSIS
• GOOD IF LOCALISED TO LUNGS.
• BAD: ELDERLY, IMMUNOSUPRESSED,
MULTIDRUG RESISTENT TB.
TUMORS
• LUNG CARCINOMA IS THE MOST COMMON
CAUSE OF CANCER DEATH IN THE WEST.
• TYPES: SCC, ADENOCARCINOMA, SMALL CELL
CARCINOMA AND LARGE CELL CARCINOMA.
• SMALL CELL…. CHEMOTHERAPY
• NONSMALL…. SURGERY, BUT ALSO CHEMO.