Chapter 19 Respiratory System Diseases

Pneumonia

an infection that inflames the air sacs in one or both lungs

air sacs may fill with fluid or pus

severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

causes coronavirus disease 2019 (COVID-19)

it leads to a range of clinical manifestation from asymptomatic cases to severe disease that can lead to acute respiratory distress syndrome (ARDS) and death

SARS-CoV-2 pathogenesis

spike proteins of this disease bind the angiotensin-converting enzyme 2 (ACE2) receptor in host cells

transmembrane serine protease 2 (TMPRSS2) cleaves the S protein to initiate viral fusion with the cell membrane

interferon signaling and immune response

SARS-CoV-2 therapies

anti-SARS_CoV-2 therapies - Paxloid and Remdesivir

monoclonal antibodies

mRNA COVID-19 vaccine

anti-SARS-CoV-2 therapies

Paxloid

Remdesivir

monoclonal antibodies (mAbs)

target the SARS-CoV-2 spike protein

shown clinical benefits in treating SARS-CoV-2 infection

Streptococcus pneumoniae

bacteria that causes 60-70% of all bacterial pneumonias

small cells arranged in pairs and short chains

Diseases caused by Streptococcus pyogenes

strep throat or pharyngitis

cellulitis

scarlet fever

streptococcal toxic shock syndrome

impetigo

rheumatic fever

necrotizing fever

post-streptococcal glomerulonephritis

Group A Streptococcus

one of the most important causes of acute upper respiratory tract infection

common cold

causes by adenoviruses

Flu

contagious respiratory illness caused by influenza viruses that infect the nose, throat, and sometimes the lungs

it can cause mild to severe illness, and at times can lead to death

best way to prevent flu is by getting a vaccine each year

antigenic drift

consists of small changes (or mutations) in the genes of influenza viruses that can lead to changes in the surface proteins of the virus, HA (hemagglutinin) and NA (neuraminidase)

antigenic shift

an abrupt, major change in a flu A virus, resulting in new HA and/or new HA and NA proteins in flu viruses that infect humans

antigenic drift

antigenic shift

two ways the influenza virus is constantly changing

RSV (respiratory syncytial virus)

virulence factor that produces giant multinucleated cells or syncytia

mycobacteria: acid-fast bacilli

gram-positive irregular shaped bacilli

strict aerobes

acid-fast staining

aid-fast staining

certain group of bacteria is considered “acid-fast” because they resist the acid wash —> high content of mycolic acids in their cell walls

ex. mycobacteria

mycobacterium tuberculosis virulence factors

produces no exotoxins or enzymes that contribute to infectiousness

1. mycolic acid

2. cord factor

mycolic acid

gives mycobacterium tuberculosis its defense against the complement system, free radicals and phagocytosis

virulence factor

cord factor

prevents destruction of mycobacterium tuberculosis by lysosomes and increases inflammation

virulence factor

tuberculosis

predisposing factors: inadequate nutrition, weakened immune system, poor medical care, lung damage, genetics

estimate 1/3rd of population and 15 million in US carry the bacterium

highest cases: above 65 years, AIDS patients, and immigrant from Southeast Asia, Latin America, and Africa

very resistant, can survive for 8 months in the fine aerosol particles

transmitted by respiratory droptlets

mycobacterium tuberculosis

causes tuberculosis

tuberculosis

5% to 10% of infected people develop clinical disease

untreated, the disease progresses slowly

majority of these cases are contained in the lung

clinical tuberculosis types

primary

secondary

extrapulmonary

primary tuberculosis

infectious dose only 10 cells

phagocytosed by macrophages and multiply intracellularly

after 3-4 weeks, the immune system attacks, forming tubercles (tubercle: bacilli surrounded by WBCs)

2 types:

asymptomatic

progressive

types of primary tuberculosis

asymptomatic

progressive

asymptomatic primary tuberculosis

body’s immune system is strong

lymphocytes manage to contain the bacteria and the infection does not spread further

progressive primary tuberculosis

the immune system is weak

the lymphocytes cannot contain the TB bacteria and it rapidly spreads

the infected person develops symptoms and falls ill

secondary/reactivation tuberculosis

the immune system is initially strong and contains the TB bacteria, but subsequently weakens and cannot control it

the bacteria first go into a dormant state but then get reactivated and subsequently spread aggressively

secondary tuberculosis

if patient does not recover from primary tuberculosis, reactivation of bacilli can occur

tubercles will drain into the bronchial tubes and upper respiratory tract

gradually the patient experiences more severe symptoms

• violent coughing, greenish or bloody sputum, fever, anorexia, weight loss, fatigue

untreated, 60% mortality rate

extrapulmonary tuberculosis

bacilli disseminate to regional lymph nodes, kidneys, long bones, genital tract, brain, and meninges

these complications are usually terminal

tubercles

granulomas with large influx of mononuclear cells into the lungs that occur in tuberculosis

tuberculosis diagnosis

1. in vivo or tuberculin testing —> mantoux test

2. x-rays

3. direct identification of acid-fast bacilli in specimen

4. cultural isolation and biochemical testing

no

is mantoux test positive means the person has tuberculosis? 

mnatoux test

local intradermal injection of purified protein derivative (PPD); look for bed bump to form in 48-72 hours

tuberculosis management and prevention

6-24 months of at least 2 drugs from a list of 11

one pill regimen called Rifater (contains 3 different antibiotics)

vaccine based on attenuated bacilli strain used in other countries

C. diphtheriae pathology

2 stages:

1. local infection: upper respiratory tract inflammation - sore throat, nausea, vomiting, swollen lymph nodes 

2. diptherotoxin production: target organs - primarily heart and nerves

the toxin kills healthy tissues in the respiratory system and forms dead tissue with a thick, gray coating that build up in the throat or nose that is know as “pseudomembrane” - the hallmark of respiratory diphtheria is a pseudomembrane

C. diphtheriae epidemiology

reservoir of healthy carriers; potential for diphtheria is always present

most cases occur in non-immunized children living in crowded, unsanitary conditions

acquired via respiratory droplets from carriers or actively infected individuals

C. diphtheriae pathogenesis

diptheria Toxin B part binds host cell receptor

diptheria Toxin A part enters the host cells

C. diphtheriae detection

culture

toxigenicity testing: Elk test - detection of the toxin by the immunodiffusion assay - gold standard essay 

molecular test by PCR of toxin

C. diphtheriae treatment

antitoxin, penicillin, or erythromycin

C. diphtheriae prevention

toxoid vaccine series and boosters