BMS250 - Wk 6

Pressure Profiles Recap

• Normal systolic and diastolic pressures in the pulmonary artery are about 25 and 8 mm Hg, respectively.
• The mean pulmonary arterial pressure is normally 15 mm Hg, compared to 93 mm Hg in the aorta.
• Driving pressure, which is normally 10 mm Hg, is the difference between the mean pressure in the pulmonary artery (15 mm Hg) and the pressure in the left atrium (5 mm Hg).

Pulmonary Hypertension (PH)

• PH is a heterogenous disease involving pathogenic remodeling of the pulmonary vasculature.
• This remodeling increases pulmonary artery pressure and vascular resistance.
• The mean pulmonary artery pressure (mPAP) used to diagnose PH has been lowered from ≥25 mmHg to >20 mmHg to emphasize earlier detection.

Sixth World Symposium on Pulmonary Hypertension Classification (2018)

• PH is classified based on hemodynamic parameters and clinical features, categorized as precapillary, capillary, or postcapillary.
• Classification includes:
  • Pulmonary Arterial Hypertension (PAH)
  • Left heart disease
  • Chronic lung disease or sleep-disordered breathing
  • Chronic Thromboembolic Pulmonary Hypertension (CTEPH)
  • Miscellaneous

Histopathology of Pulmonary Hypertension

• Late in gestation, pulmonary arteries have thick walls.
• After birth, these vessels dilate, and the walls become thin.
• Mild pulmonary hypertension causes thickening of the media.
• Severe pulmonary hypertension causes extensive intimal fibrosis and muscle thickening.
• Pulmonary hypertension grades 1, 2, and 3 are generally reversible, but grades 4 and above are generally not.

Pulmonary Hypertension - Pathobiology

• Normal pulmonary artery structure.
• Media and intima thickening occurs in small vessels.
• Idiopathic PAH is muscularized in medium-sized pulmonary arteries.
• Telangiectatic dilations can occur in the pulmonary artery, forming plexiform lesions.
• Complete lumen obliteration may occur with loose collagen.
• Medium-sized veins can be obliterated by loose connective tissue with an organized thrombus.

Pulmonary Arterial Hypertension (PAH)

• PAH is a rare precapillary disorder caused by increased pulmonary arterial tone.
• PAH may be idiopathic or hereditary, associated with mutations in genes like BMPR2, ALK1, and endoglin.
• Drugs or toxins are exogenous factors that can contribute to the development of PAH.
• Endothelial dysfunction, increased pulmonary arterial tone, and vascular remodeling can cause increased pulmonary vascular resistance (PVR).

Idiopathic PAH (IPAH)

• IPAH is a progressive disease leading to right heart failure and early mortality.
• IPAH affects women more than men by ~3.1-fold; women in their 20s and 30s are often affected
• Hemodynamics at diagnosis is more severe in women, leading to less favorable prognosis compared to men.
• Pathologic changes to pulmonary arterial compliance result in a progressive increase in total pulmonary vascular resistance (PVR).
• To preserve cardiac output (CO) in the face of elevated right ventricular afterload, right ventricular work must increase.

Pulmonary Arterial Hypertension (PAH): Clinical Picture

• The onset of PAH can be insidious with dyspnea.
• In end-stage PAH, cardiac output (CO) declines, reducing the mean pulmonary artery pressure (mPAP).
• Extrapulmonary vascular manifestations can include overactivation of neurohumoral signaling, renal failure, and volitional muscle atrophy due to deconditioning.
• Severe pulmonary hypertension can lead to plexiform lesions eventually leading to cor pulmonale.
• Recent use of prostacyclin analogs, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors has led to a 5-year survival rate of about 30%.
• Heart-lung transplantation is often a necessary treatment.

Pulmonary Edema

• Defined as an abnormal accumulation of fluid in the interstitial and alveolar spaces of the lung.
• An important and life-threatening complication due to a variety of heart and lung diseases.

Frequent Causes of Pulmonary Edema

• Increased capillary hydrostatic pressure due to:
  • Cardiogenic pulmonary edema (e.g., myocardial infarction, mitral stenosis, heart failure)
  • Neurogenic pulmonary edema
  • Pulmonary venoocclusive disease
• Increased capillary permeability due to:
  • Toxin-mediated injury (inhaled or circulating)
  • Sepsis
  • Radiation
  • Oxygen toxicity
  • Acute Respiratory Distress Syndrome(ARDS)
  • Transfusion-related acute lung injury
• Decreased colloid osmotic pressure due to:
  • Excessive administration of intravenous fluids
  • Hypoalbuminemia

Interstitial-Alveolar Pulmonary Edema

• The lymphatics become overloaded.
• Pressure in the interstitial space increases, causing fluid to spill over into the alveoli.
• The alveolar epithelium may be damaged, increasing its permeability.
• Results in the presence of protein and red cells in the alveolar fluid.

Interstitial Edema

• Increased lymph flow occurs from the lung with widened lymphatics.
• Perivascular and peribronchial engorgement (cuffing).
• Has little direct effect on pulmonary function.
• Diagnosed with some radiologic changes (Septal lines).

Alveolar Edema

• Fluid moves across the epithelium into the alveoli.
• Edematous alveoli shrink due to collapse caused by pressure.
• Ventilation is prevented.
• Shunting and hypoxemia are inevitable when alveoli are perfused but not ventilated.

Pulmonary Edema on Plain Chest Radiography

• Pulmonary edema due to heart failure results in a reduced ejection fraction.
• High-altitude pulmonary edema may affect heart size.

Pulmonary Edema: Clinical Picture & Management

• Symptoms:
  • Difficulty breathing (dyspnea) or extreme shortness of breath that worsens when lying down (orthopnea).
  • A feeling of suffocating or drowning that worsens when lying down.
  • Cough that produces frothy sputum with blood.
  • Rapid, irregular heartbeat (palpitations).
  • Anxiety, restlessness.
  • Cold, clammy skin.
  • Wheezing, gasping for breath.
• Management:
  • Diuretics
  • Inotropes
  • Antihypertensives
  • Morphine (acutely)

Pulmonary Hypertension Associated with Lung Disease

• The second most common cause of pulmonary hypertension (PH).
• Chronic obstructive pulmonary disease (COPD).
• Interstitial lung disease.
• Mixed obstructive/restrictive pathophysiology: bronchiectasis, cystic fibrosis.
• Sleep-related respiratory disorders.
• PH is usually modest showing that 90% of COPD patients have mPAP >20 mmHg, and only 5% of patients have mPAP >35 mmHg.
• Severe PH with primary lung disease has a challenging clinical outcome.

Venous Thromboembolism (VTE)

• VTE encompasses deep venous thrombosis (DVT) and pulmonary embolism (PE).
• VTE causes cardiovascular death, chronic disability, and emotional distress.
• Skin ulceration can happen in the lateral malleolus from post-thrombotic syndrome of the leg.

Venous Thrombi

• Most commonly originate in the deep veins of the lower extremities.
• Origin can also be in the upper extremities, right side of the heart, and pelvic veins.
• Pathogenesis is described by Inflammation & Virchow's triad:
  1. Stasis of blood
  2. Alterations in the blood coagulation system (hypercoagulability)
  3. Abnormalities of the vessel wall (intimal injury)

Prothrombotic States: Hypercoagulability

• Most common autosomal dominant genetic mutations:
  1. Factor V Leiden, which causes resistance to the endogenous anticoagulant activated protein C.
  2. Prothrombin gene mutation, which increases the plasma prothrombin concentration.
• Antithrombin, protein C, and protein S are naturally occurring coagulation inhibitors whose deficiencies are associated with VTE, although but are rare.
• Antiphospholipid antibody syndrome is an acquired thrombophilic disorder that predisposes to venous and arterial thrombosis.

Clinical Risk Factors for Venous Thromboembolisms

• Cancer
• Obesity
• Cigarette smoking.
• Systemic arterial hypertension.
• COPD.
• Chronic Kidney Disease.
• Long-haul air travel.
• Estrogen-containing contraceptives.
• Pregnancy.
• Postmenopausal hormone replacement.
• Surgery and Trauma.
• Sedentary lifestyle, A sedentary lifestyle of watching 2 hours a day associated with a 40% increased likelihood of fatal PE per recent Japanese study.

Inflammation-Linked Conditions Triggering DVT (Deep Vein Thrombosis) & PE (Pulmonary Embolism)

• Ulcerative colitis.
• Crohn's disease.
• Rheumatoid arthritis.
• Psoriasis.
• Diabetes mellitus, type 2.
• Obesity/metabolic syndrome.
• Hypercholesterolemia, especially elevated LDL.
• Lipoprotein(a).
• Pneumonia.
• Acute coronary syndrome.
• Acute stroke.
• Cigarette smoking.
• Sepsis/septic shock.
• Erythropoiesis-stimulating agents.
• Blood transfusion.
• Cancer.

Pulmonary Embolism (PE)

• Thrombi form in large veins and travel to the lungs where they become lodged, occluding the pulmonary circulation.
• PE is associated with significant morbidity and mortality and can be challenging to diagnose.
• Types:
  • Venous thrombi.
  • Nonthrombotic emboli: fat, air, and amniotic fluid.

Interaction Between Venous Thromboembolism (VTE) and Atherothrombosis

• Share similar risk factors and pathophysiology include inflammation, hypercoagulability, and endothelial injury.
• Patients experiencing PE (Pulmonary Embolism) are more than twice as likely to have a future myocardial infarction or stroke.
• Patients with myocardial infarction or stroke are more than twice as likely to suffer a future PE (Pulmonary Embolism).

Classifications of Acute Pulmonary Embolism

• Massive (High-risk) PE:
  • Classified at affecting 5–10% of PE cases
  • Involves systemic arterial hypotension and extensive thrombosis affecting at least half of the pulmonary vasculature.
  • Symptoms: Dyspnea, syncope, hypotension, and cyanosis.
  • Can lead to cardiogenic shock and multisystem organ failure.
• Submassive (Intermediate-risk) PE:
  • Classified at affecting 20–25% of PE cases
  • Involves right ventricular (RV) dysfunction despite normal systemic arterial pressure.
  • The combination of right heart failure and the release of cardiac biomarkers (troponin) indicates a high risk of clinical deterioration.
• Low-risk PE:
  • Classified at affecting 65–75% of PE cases
  • Associated with an excellent prognosis.

Clinical Features of a Pulmonary Embolism (PE)

• Small Emboli
  • Frequently goes unrecognized
  • Repeated emboli may result in pulmonary hypertension
• Medium-sized Emboli
  • Sometimes induces pleuritic pain, dyspnea, and slight fever
  • Cough may produce blood-stained sputum
  • May produce pleural friction rub
  • Chest radiograph is often normal or nearly so
• Massive Emboli
  • Leads to hemodynamic collapse with shock, pallor, and cardiac arrest
  • Hypotension with rapid, weak pulse and neck vein engorgement
  • Sometimes fatal

Pulmonary Hypertension Associated with Chronic Thromboembolic Disease (CTEPH)

• Development of pulmonary hypertension (PH) after chronic thromboembolic obstruction of the pulmonary arteries.
• The incidence of CTEPH following a single pulmonary embolic event is difficult to determine accurately.
• Approximately 3 to 7% of patients develop CTEPH.
• Notably, 25% of patients with CTEPH have no history of clinical venous thromboembolism and are suggest of CTEPH.

Chronic Pulmonary Embolism

• An obstructive vascular pattern may affect segmental pulmonary arteries.
• It can occur in patients with exertional dyspnea.
• It can occur in patients with remote histories of pulmonary embolism
• Pulmonary angiography shows pulmonary artery stricture, webbing, and severe dearborization pattern classic for CTEPH.
• Fibrotic, chronic clot specimens resected during surgical pulmonary endarterectomy, which is curative in most CTEPH patients.

Cor Pulmonale

• Defined as right ventricular failure due to excessively high pulmonary artery pressures.
• Causes:
  • Pulmonary emboli.
  • Pulmonary vascular disease (e.g., collagen vascular disease such as scleroderma).
  • Parenchymal disease (e.g., COPD, pulmonary fibrosis).

Cor Pulmonale: Pathology

• Transverse section of the heart from a patient with primary (idiopathic) pulmonary hypertension shows:
  • Markedly hypertrophied right ventricle.
  • Right ventricular free wall thickness is nearly equal to that of the left ventricular wall.
  • Right ventricle is dilated.
  • Straightened interventricular septum due to remodeling process.

Causes of Cor Pulmonale

• Parenchymal Diseases of the Lung
  • Chronic bronchitis and emphysema
  • Pulmonary fibrosis (from any cause)
  • Cystic fibrosis
• Pulmonary Vascular Diseases
  • Recurrent pulmonary emboli
  • Primary pulmonary hypertension
  • Peripheral pulmonary stenosis
  • Intravenous drug abuse
  • Residence at high altitude
  • Schistosomiasis
• Congenital Heart Diseases
• Impaired Movement of the Thoracic Cage
  • Kyphoscoliosis
  • Pickwickian syndrome
  • Pleural fibrosis
  • Neuromuscular disorders
  • Idiopathic hypoventilation

WHO Group 5 PH: Miscellaneous

• Encompasses pulmonary hypertension (PH) due to unclear or multifactorial mechanisms.
• Sarcoidosis.
• Sickle Cell Disease (and other hemoglobinopathies): etiology includes hemolysis, hypoxemia, thromboembolism, chronic high CO, and chronic liver disease that occurs in about 6-10% of patients.
• Schistosomiasis: Globally, this is a common cause of PH in the setting of hepatosplenic disease and portal hypertension.

Vasculitis

• A number of distinct disorders characterized by inflammation of and damage to blood vessels.
• Vessel lumen is usually compromised, which is associated with ischemia.
• Can distinguish Granulomatous, eosinophilic, lymphoplasmacytic, or neutrophilic.
• There can be primary disease, manifesting of a primary component.
• There can be secondary disease from a component.
• Defined by the size, type, and location of the affected vasculature.

Vasculitis—Current Classification Scheme

• Based vessel size: small, medium, and large.
• Large vessels include the aorta and its largest branches, clinically affecting the extremities and head/neck.
• Medium-sized vessels refer to the visceral arteries, such as renal, hepatic, coronary, and mesenteric.
• Small vessels include capillaries, venules, and arterioles.

Vasculitis: Lung Involvement

• Most commonly seen with primary, idiopathic, small-vessel, or antineutrophil cytoplasmic antibody-associated vasculitides.
  • Wegener's Granulomatosis
  • Microscopic Polyangiitis
  • Churg-Strauss Syndrome
• Primary, idiopathic medium and large-vessel vasculitis, primary immune complex–mediated vasculitis, and secondary vasculitis are all capable of presenting with lung involvement..

Allergic Granulomatosis and Angiitis (Churg-Strauss Syndrome)

• Occurs in young people with asthma.
• Widespread necrotizing lesions can be founded in small and medium-sized arteries.
• Granulomas and intense eosinophilic infiltrates found in and around blood vessels, leading to fibrinoid necrosis, thrombosis, and aneurysm formation.
• Untreated causes a poor prognosis, although corticosteroid therapy is almost always effective.

Granulomatosis with Polyangiitis (formerly Wegener Granulomatosis)

• Systemic necrotizing vasculitis of unknown etiology, with granulomatous lesions of the nose, sinuses, lungs, and kidneys.
• Affects Men usually greater than women at fifth and sixth decades.
• Over 90% of patients affected have a positive ANCA.
• The most prominent pulmonary feature is persistent bilateral pneumonitis, nodulaar infiltrates undergo cavitation similar to tuberculosis

Sarcoidosis

• A systemic disorder characterized by noncaseating granulomatous inflammation at sites of disease.
• Often multisystemic - any organ can be involved.
• Most commonly: lungs and intrathoracic lymph nodes.
• Differential diagnosis is not specific between mycobacterial, fungal infections, or malignancy.

Ethnology of Sarcoidosis

• Etiology includes associations with insecticides cigarette smoking.
• Associated with microbes such a myco bacterial or propio bacterial infection where they can cause infection.
• Genes are associated with environmental interactions.
• Associated with Microbiomes

Sarcoidosis Epidemiology

• Sarcoidosis is found worldwide.
• Highest prevalence in Scandinavia and the U.S. Southeast.
• Peak onset is in middle-aged adults (40-55 years old), possibly bimodal (younger males vs. older females).
• Increased frequency and higher mortality are observed in Black Americans.
• Higher prevalence among first-degree relatives and twin siblings.
• Frequency of lupus pernio, Löfgren syndrome, and cardiac involvement is associated with race, ethnicity, and gender.

Sarcoidosis: Genetic Associations

• Family and Case Study shows how it provides genetic influence.
• 10% of clustering cases were from cases of Sarcoidosis.
• The frequency of lupus pernio, Löfgren syndrome, cardiac involvement and other clinical sarcoidosis manifestations is associated with race, ethnicity and gender, supporting a genetic basis for this disease.
• Genetic polymorphisms have been shown linked with disease risk and clinical phenotype, with the strongest associations identified within the HLA genes of the major histocompatibility complex (MHC) locus.

Etiology & Pathogenesis of Sarcoidosis

• Epidemiologic studies show association is linked to insecticides or cigarette smoking
• Microbes a a hypothesized reason why sarcoidosis triggers in genetically susceptible indiciduals.
• Interaction between Gene-environment
• Host is also influenced by microbiome

Pathology in Noncaseating granulomas

• Hallmark occurs from The granulama.
• Occurs over time with with a local accumulation of inflammatory responses.
• Lymph nodes are discrete by epithelium

Clinical Stages of Sarcoidosis Stages

• Stage 0: X-Rays are clear and normal to suggest pulmonary sarcoidosis.
• Stage 1: granulomas are now visible within lymph nodes only.
• Stage 2: showing that Granulomas in lymph nodes within either lungs.
• Stage 3: Granulomas in lungs themselves only.
• Stage 4: Showing more fibrosis showing permanent scarring of your lungs.

Lung Function is the last method of test

• For any abnormalities
• For volumes, or capacities to decrease.

Extrapulmonary manifestations of the Sarcoid lung disease

• Symptoms show up with skin disorder on the trunk

Pulmonary fibrosis

• Systemic Disorder,

Other outcomes are

• Sarocadosis as a test
• And Pulmonary in System

Occupational lung disease

• Pneumoconioses dust is either Inorganic or organic in reaction from hyper sensitive state.

Outcomes for disease

• Occurs from connective tissues or even diseases

Ocupactional Lung

• It can be interact as one in

Asbestos

• Has a hydrated component, is commercial.

Other

• Connective , pulmonary and interstitial

More risk

• For pneumonia
• For cancers of lung which may lead to mesothelioma
• This causes long term issues

Chronic and Progressive

• With no cure
• High in volume for lungs and macrophages
• Leads to macrophages accumulating inside the lungs itself that causes tissue reaction.

Microbiology of Major Bacterial Infections of Lower Respiratory Tract

• The learning objectives focus on key bacterial pathogens and types of pneumonia affecting the lower respiratory tract.

Gram-Positive Bacteria

• Important bacteria include Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae.

Gram-Negative Bacteria

• Key bacteria include Haemophilus influenzae, Bordetella pertussis & parapertussis, Klebsiella pneumoniae, and Pseudomonas aeruginosa.

Bacteria Causing “Atypical Pneumonia”

• Include Legionella, Mycoplasma pneumoniae, and Chlamydia trachomatis.

Types of Pneumonia

• Community-acquired pneumonia (CAP) can be typical (S. pneumoniae) or atypical (Mycoplasma, Chlamydia, Legionella).
• Nosocomial pneumonia is often caused by gram-negative pathogens.
  • Includes hospital-acquired pneumonia (HAP) and ventilator-acquired pneumonia (VAP).
• Other conditions to be aware of: Pulmonary abscess & Anaerobic infections and Tuberculosis.

Classification of Bacteria: Staining

• Hans Christian Gram developed the staining method using crystal violet dye in 1884.
• Gram-positive bacteria stain blue because the dye is retained by the thick peptidoglycan cell wall.
• Gram-negative bacteria stain red.
• Gram-negative and gram-positive bacteria stain differently because their cell walls are different.
• Gram-negative and gram-positive bacteria cause different types of infections, and different types of antibiotics are effective against them.

Classification of Bacteria: Oxygen

• Aerobic bacteria need oxygen for growth.
• Anaerobic bacteria have difficulties growing when oxygen is present.
• They are a large part of the normal resident flora on mucous membranes (mouth, lower gastrointestinal tract, vagina).
• They can cause disease when mucous membranes are disrupted.
• Anaerobes from outside the body sometimes cause disease when they enter breaks in the skin or are consumed.

Classification of Bacteria: Morphology

• Spherical bacteria are called cocci.
• Cylindrical bacteria are called bacilli.
• Spiral bacteria are called spirochetes.

Gram-Positive Cocci

• Staphylococcus aureus and Streptococcus pyogenes are two of the most important human pathogens.
• They are nonmotile and do not form spores.
• Microscopically, staphylococci appear in grapelike clusters, whereas streptococci are in chains.
• Biochemically, staphylococci produce catalase, which degrades hydrogen peroxide, whereas streptococci do not.

Staphylococci and Streptococci

• Both staphylococci and streptococci are gram-positive cocci but are differentiated by two main criteria:
• Microscopically, staphylococci appear in grapelike clusters, whereas streptococci are in chains.
• Biochemically, staphylococci produce catalase, which degrades hydrogen peroxide, whereas streptococci do not.

Staphylococcus aureus: Microbiologic Properties

• Spherical gram-positive cocci arranged in irregular grapelike clusters
• Produces catalase, whereas no streptococci do (catalase degrades H2O2 into O2 and H2O).
• Catalase is an important virulence factor

Staphylococcus: Three Species

• The three species are: S. aureus, S. epidermidis, and S. saprophyticus.
• S. aureus is distinguished from the others primarily by coagulase production

Staphylococcus aureus: β-lactamase

• It produces an enzyme that degrades many, but not all, penicillins.
• β-Lactamase–resistant penicillins are used, including methicillin & nafcillin.
• Many strains of S. aureus are resistant to β-lactamase–resistant penicillins thus Methicillin-resistant Staphylococcus aureus (MRSA).
• MRSA accounts for >50% of S. aureus strains isolated from hospital patients and is also very commonly seen in the community but at a slightly lower frequency.

Transmission of Staphylococci

• Humans are the reservoir.
• The nose is the main site of colonization of S. aureus, and approximately 30% of people are colonized at any one time.
• People who are chronic carriers of S. aureus in their nose have an increased risk of skin infections caused by S. aureus.
• The skin, especially of hospital personnel and patients, is also a common site of colonization.
• Hand contact is an important mode of transmission, and handwashing decreases transmission.

Pathogenesis of S. aureus: Toxigenic

• It produces 3 Exotoxins:
• Enterotoxin causes food poisoning.
• Toxic Shock Syndrome Toxin is associated with toxic shock in tampon-using menstruating women, individuals with wound infections, and patients with nasal packing used to stop bleeding from the nose.
• Exfoliatin causes “scalded-skin” syndrome in young children, with localized production resulting in bullous impetigo.

Pathogenesis of S. aureus: Pyogenic

• S. aureus causes disease both by producing toxins and by inducing pyogenic (pus-producing) inflammation.
• Typical lesions include abscess, folliculitis, and impetigo.
• It may disseminate via the bloodstream.
• Foreign bodies (sutures and intravenous catheters) are predisposing factors to infection.
• Other forms of disseminated diseases include osteomyelitis and arthritis.

S. Aureus: Pneumonia

• It is a cause of Hospital-acquired pneumonia.

S. epidermidis

• It causes infections of intravenous catheter sites and prosthetic devices.

S. saprophyticus

• It is associated with Urinary tract infections.

Streptococci: Important Properties

• These are spherical gram-positive cocci arranged in chains or pairs.
• All streptococci are catalase negative.

Classification of Streptococci: Groups

• Arranged into groups A–U (known as Lancefield groups).
• They are based on antigenic differences in C carbohydrate.
• Group A streptococci (S. pyogenes) is one of the most important human pathogens.
• S. pyogenes is the most frequent bacterial cause of pharyngitis and a very common cause of skin infections.
• The growth of S. pyogenes on agar plates is inhibited by the antibiotic bacitracin, which is an important diagnostic criterion.

Classification of Streptococci: Type of Hemolysis

• α-Hemolytic creates a green zone around colonies due to incomplete lysis of red blood cells.
• β-Hemolytic streptococci create a clear zone around colonies because of complete lysis of red blood cells (enzymes called streptolysin O and S).
• Nonhemolytic (γ-hemolysis) present.

Transmission of Streptococci

• Most streptococci are part of the normal flora of the human throat, skin, and intestines.
• They produce disease when they gain access to tissues or blood.
• Viridans streptococci and S. pneumoniae are found chiefly in the oropharynx.
• S. pyogenes is found on the skin and in the oropharynx in small numbers.
• S. agalactiae occurs in the vagina and colon.
• The enterococci and anaerobic streptococci are located in the colon.

S. pyogenes (group A Streptococcus)

• This is the leading bacterial cause of pharyngitis and cellulitis.
• It can result in Impetigo, erysipelas, necrotizing fasciitis, scarlet fever, and streptococcal toxic shock syndrome.
• It is the inciting factor of rheumatic fever, and acute glomerulonephritis (two important immunologic diseases).

Diseases of S. pyogenes

• Pyogenic diseases include pharyngitis and cellulitis and are Induced locally at the site of the organisms in tissue.
• Toxigenic diseases include scarlet fever and toxic shock syndrome, which causes widespread systemic symptoms in areas of the body where there are no organisms.
• Immunologic diseases include rheumatic fever and acute glomerulonephritis (AGN). The Antibody against a component of the organism cross-reacts with normal tissue or forms immune complexes that damage normal tissue.

S. viridans

• Is part of the normal flora of the human pharynx.
• S. viridans is the most common cause of subacute bacterial endocarditis.

S. agalactiae

• This is the leading cause of neonatal sepsis and meningitis.

Streptococcus pneumoniae

• Is a cause of Pneumonia, bacteremia, meningitis, and infections of the upper respiratory tract such as otitis media, mastoiditis, and sinusitis.
• Pneumococci are the most common cause of community-acquired pneumonia

Streptococcus Pneumoniae

• Pneumococci are spherical gram-positive bacteria of the genus Streptococcus.
• Bacteria grow in chains or pairs and the name Streptococcus comes from the Greek Streptos = “twisted,” and kokkos = "berry".

Streptococcus Pneumoniae

• α-hemolytic group that characteristically produces a greenish color on blood agar because of the reduction of iron in hemoglobin

S. Pneumoniae: Pathogenesis

• The S. Pneumoniae virulence factors include:
• Polysaccharide capsules interfere with phagocytosis. - C-substance (C-polysaccharide) reacts with C-reactive protein (CRP). CRP is an acute-phase protein and is nonspecifically elevated in response to inflammation and is measured via serum reaction with pneumococcal carbohydrate. Elevated CRP is also a predictor of heart attack risk. - Pneumolysin causes α-hemolysis. - IgA protease enhances colonization of the upper respiratory tract.
• Pneumococci multiply in tissues and cause inflammation. In the alveoli, fluid and blood cells pour out, leading to consolidation. During recovery, pneumococci are phagocytized, and the consolidation resolves.

Transmission of Pnemococci

• Humans are natural hosts (no animal reservoir): 5%–50% of the healthy population (in the oropharynx).
• It results most often when predisposing factors are present:
  1. cerebral impairment that can depress the cough reflex and increase aspiration of secretions (2) abnormality of the respiratory tract (e.g., viral infections), (3) abnormal circulatory dynamics (e.g., pulmonary congestion and heart failure) (4) splenectomy (5) certain chronic diseases (sickle cell anemia; nephrosis)

Gram-Negative Bacteria

• Important gram negative bacteria include Haemophilus influenzae, Bordetella pertussis & parapertussis, Klebsiella pneumoniae, and Pseudomonas aeruginosa.

Haemophilus Influenzae

• Normal component of the upper respiratory tract flora

Infections Caused by Haemophilus Influenzae

• Includes pneumonia in immunocompromised and HIV-positive persons.

Bordetella pertussis & parapertussis

• The bacteria are small, encapsulated coccobacilli, Bordetella pertussis is also known as whooping cough which can cause a mild pertussis-like illness.
• It is an important cause of morbidity and mortality worldwide (2.4 million cases and 160,000 deaths each year)
• Pertussis vaccines are available
• vaccination have had significant effects on lowering the incidence of whooping cough

Pseudomonas aeruginosa

• Causes localized and systemic illness and presents with virtually any tissue being infected
• eye keratitis and endophthalmitis following trauma
• ear (external otitis, or swimmer's ear, and invasive and necrotizing otitis externa), Skin urinary tract and CNS infections
• respiratory tract (pneumonia in individuals with chronic lung disease, congestive heart failure, or cystic fibrosis, in patients who have been intubated or are on ventilators for longer than a few days)
• gastrointestinal (GI) tract (mild diarrheal illness in children to severe, necrotizing enterocolitis in infants and neutropenic cancer patients)
• Individuals with impaired immune defenses are most at risk.

Klebsiella pneumoniae

• large, nonmotile bacilli with an abundant capsule.
• can cause necrotizing lobar pneumonia in individuals compromised by alcoholism, diabetes, or chronic obstructive pulmonary disease.
• K. pneumoniae also causes urinary tract infections and bacteremia, particularly in hospitalized patients.

Bacteria causing “Atypical Pneumonia”

• The bacteria causing Atypical Pneumonia are: Legionella, Mycoplasma pneumoniae and Chlamydia trachomatis

Mycoplasma Pneumoniae

• Is an bacteria without a cell wall

Chlamydia

• Is an atypical Pneumonia bacteria

Bacterial Pneumonia

• Community-acquired pneumonia (CAP) and Nosocomial pneumonia are broad types with varying microbial etiologies
• Typical CAP cases are mainly S. pneumoniae.
• Atypical CAP are often caused by Mycoplasma, Chlamydia, or Legionella.

Classification of Pneumonia

1. Community-acquired pneumonia (CAP)
2. Nosocomial pneumonia: 2a) hospital-acquired pneumonia (HAP) 2b) ventilator-associated pneumonia (VAP) Categories depend on differing settings and infectious agents requiring different diagnostic and therapeutic interventions

Host Defense Mechanisms:

• Intact respiratory epithelium and having a proper cough reflex.

1. Nonspecific or innate immune factors: Mucus & mucociliary clearens, Immunoglobulin A and having proper functioning cells for:
   • Splenic function
   • Complement -Neutrophils
   • Macrophages

Host Defense Mechanisms: Acquired Immunity

• The body producing serum IgG antibody specific for infections to help defend the body
• If patients lacks certain acquired immunity or have children 1 is a child or patients with High Risk in Infants & Agammaglobulinemia for their cells not properly having B-cell response