DISEASES OF THE RESPIRATPORY SYSTEM PHARMACOLOGY

LECTURE 1/2DR 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.