PULMUNOLOGY AND CARDIOLOGY (references-kaplan usmle step 2 CK lecture,harrison's principle's of internal medicine 19th ed. davidson's medicine 22nd ed,GRSMU lecture notes,class notes)

PULMONOLOGY

1. Etiology, pathogenesis of pneumonia. Classification of pneumonia.         

Definition: lung inflammation caused by bacterial or viral infection, in which the air sacs fill with pus and may become solid

Etiology

Organisms causing community-acquired pneumonia

Bacteria

• Streptococcus pneumoniae                                      

• Mycoplasma pneumoniae

• Legionella pneumophila

• Chlamydia pneumoniae

• Haemophilus influenzae

• Staphylococcus aureus

• Chlamydia psittaci

• Coxiella burnetii (Q fever,‘querry’ fever)

• Klebsiella pneumoniae(Freidländer’s bacillus)

• Actinomyces israelii

Viruses

• Influenza, parainfluenza

• Measles

• Herpes simplex

• Varicella

• Adenovirus

• Cytomegalovirus (CMV)

• Coronavirus (Urbani

SARS-associatedcoronavirus)

(SARS = severe acute respiratory syndrome)

Hospital-acquired pneumonia

Some people catch pneumonia during a hospital stay for another illness. This type of pneumonia can be serious because the bacteria causing it may be more resistant to antibiotics. People who are on breathing machines (ventilators), often used in intensive care units, are at higher risk of this type of pneumonia

Health care-acquired pneumonia

Health care-acquired pneumonia is a bacterial infection that occurs in people who are living in long-term care facilities or have been treated in outpatient clinics, including kidney dialysis centers. Like hospital-acquired pneumonia, health care-acquired pneumonia can be caused by bacteria that are more resistant to antibiotics

Aspiration pneumonia

Aspiration pneumonia occurs when you inhale food, drink, vomit or saliva into your lungs. Aspiration is more likely if something disturbs your normal gag reflex, such as a brain injury or swallowing problem, or excessive use of alcohol or drugs

Pneumonia in the immunocompromised patient

Bacterial - Tuberculosis (TB) and non-TB mycobacteria, mainly Mycobacterium avium complex (MAC)

Fungi -Pneumocystis jirovecii, Aspergillus fumigatus, Histoplasma capsulatum, Mucor species, Coccidioides immitis, and Cryptococcus neoformans

Viruses -Cytomegalovirus (CMV), influenza, herpes simplex virus (HSV), varicella zoster virus (VZV)

Parasites -Strongyloides species

Pathogenesis of pneumonia:

Pneumonia frequently starts as an upper respiratory tract infection that moves into the lower respiratory tract. It is pneumonitis (lung inflammation) combined with consolidation (liquid in spaces normally inflated with air)

Pneumonia fills the lung's alveoli with fluid, hindering oxygenation. The alveolus on the left is normal, whereas the one on the right is full of fluid from pneumonia

Viral

Viruses may reach the lung by a number of different routes. Respiratory syncytial virus is typically contracted when people touch contaminated objects and then they touch their eyes or nose. Other viral infections occur when contaminated airborne droplets are inhaled through the mouth or nose.

 Once in the upper airway, the viruses may make their way in the lungs, where they invade the cells lining the airways, alveoli, or lung parenchyma. Some viruses such as measles and herpes simplex may reach the lungs via the blood. The invasion of the lungs may lead to varying degrees of cell death.

 When the immune system responds to the infection, even more lung damage may occur.Primarily white blood cells, mainly mononuclear cells, generate the inflammation. As well as damaging the lungs, many viruses simultaneously affect other organs and thus disrupt other body functions. Viruses also make the body more susceptible to bacterial infections; in this way, bacterial pneumonia can arise as a co-morbid condition.

Bacterial

Most bacteria enter the lungs via small aspirations of organisms residing in the throat or nose. Half of normal people have these small aspirations during sleep. While the throat always contains bacteria, potentially infectious ones reside there only at certain times and under certain conditions. 

A minority of types of bacteria such as Mycobacterium tuberculosis and Legionella pneumophila reach the lungs via contaminated airborne droplets. Bacteria can spread also via the blood. Once in the lungs, bacteria may invade the spaces between cells and between alveoli, 
where the macrophages and neutrophils (defensive white blood cells) attempt to inactivate the bacteria. The neutrophils also release cytokines, causing a general activation of the immune system. This leads to the fever, chills, and fatigue common in bacterial pneumonia. 
The neutrophils, bacteria, and fluid from surrounding blood vessels fill the alveoli, resulting in the consolidation seen on chest X-ray.

Classification of pneumonia

By pathogenesis:

1) primary (in healthy persons),

2) secondary (as complication of other diseases).

By localization:

1) lobar (croupous) pneumonia,

2) bronchopneumonia,

3) interstitial pneumonia

By origin:

1) community-acquired (pneumonia is acquired in the course of

daily life - at school, work or the gym, for instance). It may be typical and atypical;

2) hospital-acquired (pneumonia occurring after more than 48 hours of admission to the hospital and is caused usually by Klebsiellapseudomonas, Enterobacter, E. coli, Proteus, Staphylococcus aureus less common, than gram negative organism);

3) atypical (organisms that cause pneumonia are: Mycoplasmapneumoniae, Legionella pneumophila, Chlamydophila pneumoniae);

4) aspiration (pneumonia is caused by aspiration of large amounts of secretions or vomitus. Anaerobic organisms are common;

5) In persons with impaired immune system (is common in patients receiving immunosuppressive drugs and in those with diseases causing defects of cellular or humoral immunity such as AIDS. Gramm negative bacilli – Pseudomonas and opportunistic organisms –

Pneumocystis carinii, Cytomegalovirus, viral and fungal infections are common)

2. Describe the symptoms of lobar pneumonia. Instrumental and laboratory methods of investigations for establish diagnosis.

Acute Lobar or Croupous Pneumonia (Pneumonic Fever) is an acuteinfective disease of the lung, characterized by homogenous consolidationof one or more lobes

Describe the symptoms of lobar pneumonia

There are 3 stages of the disease: onset, consolidation, resolution.

Stage of onset: The disease begins suddenly with a rigor and

elevation body temperature up to 39-40°C. Sometimes it follows a minor

respiratory infection of a few days duration. 

The fever then becomes continuous in character. Complaints. Pleuritic pain is felt in the affected

side, which worsens by deep breathing or coughing. Patient has dyspnea.

Cough is an early symptom, which is at first frequent and hacking. Later it

is accompanied with a little tough colorless expectoration, which soon,

however, becomes more copious and of a rusty red color.

 There aresymptoms of intoxication: severe weakness, fatigue, headache, sometimes

delirium may present. Physical examination. The state of the patient is

severe. General inspection reveals cyanotic lips and the dusky flushed

face. Sometimes there are herpetic lesions on the lips, neck and ears.

Patient has forced position, lie on the affected side. Such position relieves

chest pain. The breathing is rapid, shallow and difficult.


 Palpation of thechest gives increased tactile fremitus. The affected side may lag behind

healthy one during breathing. Pleural friction rub may be present.

Percussion of lungs gives decreased resonant sound. Auscultation of the

lungs. We may find decreased vesicular breath sounds and crackles, which

are heard during inspiration. Sometimes pleural rub may be heard.

Cardiovascular system. The pulse is accelerated.


Stage of consolidation: With the progress of the inflammation, the

febrile symptoms and rapid breathing continue to exist. Complaints.

Coughing may be associated with a sharp pain in the affected side. Sputum

is rusty red in color, later it become mucous-purulent. Physical

examination. The state of the patient is still severe. General inspection

reveals diffuse cyanosis. 

The patient during the greater course of the

disease lies on the back or on the affected side. The breathing is rapid (35-

40 per minute). The affected side of the chest is seen to expand less freely

than the opposite side. Palpation of the chest gives increased tactile

fremitus, diminished respiratory excursions.

 Pleural friction rub may be also felt. Percussion of lungs. There is dullness in percussion on the

affected side. Auscultation of the lungs. During auscultation the breath

sounds are bronchial in character. Pleural rub may be heard.

Cardiovascular system. The pulse rate is 120-140 per minute, arrhythmias

may present. Blood pressure is low. Collapse may occur in severe cases.

Heart sounds are diminished.

 Gallop rhythm may be present due tomyocarditis. Other organs and systems. Other organs and systems may be

involved too (hepatitis, nephritis, meningitis). Occasionally slight jaundice

is present. The urine is scanty, sometimes albuminous, and its chlorides are

diminished.

Stage of resolution: The state of the patient improves. The dyspnea

disappears and the affected lung begins to function again. The patient

breathes more easily, ability to sleep returns, and convalescence advances

rapidly in the majority of instances. 
Fever decreases as crisis. Collapse usually occurs during crisis. Physical examination. These various

physical signs disappear more or less rapidly during convalescence.

General inspection shows that cyanosis disappears. Palpation of the chest.

The tactile fremitus becomes less marked and gradually findings become

normal. Percussion. 
The dullness gradually disappears and normal

resonance returns. Auscultation. The bronchial breathing is gradually

replaced by bronchovesicular breathing and later by normal vesicular

breathing. Crackles reappears. Small-bubble rhonchi are heard in

increasing amount.

In unfavorable cases death may occur either from the extent of the

inflammatory action, especially if the pneumonia is double, from excessive

fever, from failure of the hearts action or general strength during the

period of the crisis, or again from the diseases, which at first assume a low

static form with delirium. Such cases are seen in persons with weakened

immunity, in the aged, and especially in the intemperate.

Instrumental and laboratory methods of investigations for establish diagnosis

Blood tests: usually show a marked neutrophil leukocytosis (to 20-

30×109/l) with a shift to the left. Increased ESR is noted. Positive blood

cultures are definitive evidence of pneumococcal infection. There may be

hypoxemia due to poor aeration of the lung and respiratory alkalosis may

occur due to hyperventilation.

Sputum examination: Sputum may be rusty red in color in early

stages of the disease. Later it becomes mucous-purulent in character.

Microscopically this consists mainly of epithelium, casts of the alveoli and

fine bronchi, together with granular matter, blood and pus corpuscles and

haematoidin crystals. Gram stain of sputum typically shows gram-positive

lancet-shaped diplococci in short chains. These streptococci can be

definitively identified as S. pneumoniae.

Pneumoccocal antigen test: Serologic test of sputum, urine and

serum for pneumococcal antigen is 3-4 times more sensitive than sputum

or blood cultures.

Chest x-ray results: depends on the stage of the disease. Findings

may be minimal or undetectable during the first several hours. Later chest

x-ray invariably shows pulmonary tissue infiltration. Dense consolidation

confined to a single lobe or segment appears within 12-18 hour.

3 Describe the symptoms of bronchopneumonia. Differential diagnosis of bronchopneumonia and lobar pneumonia

Bronchopneumonia (Bacterial Pneumonia) is an inflammation of the lungs in which only a lobule or some lobules are involved

Describe the symptoms of bronchopneumonia

Symptoms of bacterial pneumonia usually begin suddenly and often

develop during or after an upper respiratory infection, such as influenza or

a cold.
 The time between infection and the appearance of symptoms

(incubation period) can be as little as 1 to 3 days or as long as 7 to 10 days.

Complaints commonly include coughing, a high temperature to 38-

38,5°C (that may be accompanied with sweating, chills, and rigors); less

commonly shortness of breath and chest pain. Coughing at the early stages

of pneumonia may be nonproductive (dry). 3-4 days later production of

greenish or yellow sputum appears. 
There may be headache, excessive

sweating, loss of appetite, excessive fatigue, arthalgia (joint pain) or

myalgia (muscle aches). These symptoms may vary, however, depending

on how extensive the disease is and which organism is causing it

Differential diagnosis of bronchopneumonia and lobar pneumonia

Difference Between Lobar pneumonia and Bronchopneumonia
Lobar Pneumonia	Bronchopneumonia
1. Lobar pneumonia is caused by Pneumococci in 90 % of casses,  few cases are caused by klebsiella pneumonia and Staph aureus.	1. Bronchopneumonia is caused by Staphylococci, Streptococci,  H. influenzae, Proteus and Pseudomonas
2. Lobar pneumonia Occurs in otherwise  healthy individuals between 30 - 50 years of age.	2. Bronchopneumonia Occurs in infants, olds and those suffering  from chronic debilitating illness or immuno-suppression.
3. The onset of lobar pneumonia  is sudden with  high grade fever, shaking chills and  bloody or rusty sputum	3. The onset of Bronchopneumonia is insidious  with low grade fever and productive cough of purulent sputum.
4. Lobar pneumonia causes consolidation of whole lobe..	4. Bronchopneumonia produces Patchy Pneumonic Consolidation
5. Complications: bacteremia, Meningitis, Endocarditis, Septic arthritis.	5. Complications: Fibrosis, bronchiectasis, Lung abscess.

4.scribe the symptoms of pneumonia depending on the etiology and condition of the immune system, in the elderly age and in combination with alcoholism  

5.scribe the differences pneumonia caused by atypical pathogens (Chlamydia, Mycoplasma, Legionella)

Chlamydia

C. pneumoniae is a common cause of pneumonia around the world; it is typically acquired by otherwise-healthy people and is a form of community-acquired pneumonia.

C pneumoniae causes mild pneumonia or bronchitis in adolescents and young adults. Older adults may experience more severe disease and repeated infections

Pathophysiology

Chlamydiae have a unique biphasic reproductive cycle. They attach to the outer membrane of susceptible host cells and enter throughout endocytosis. Once inside, they produce cytoplasmic inclusions known as reticulate body. These replicate into multiple colonies of the infectious form, known as elementary body, which are then released during cell lysis to start the cycle again.

The mode of transmission: Respiratory secretions transmit C. pneumoniae from human to human and can cause systemic disease by hematogenous spread.  

Laboratory studies for diagnosis of chlamydial pneumonias

The Infectious Diseases Society of America and American Society of Microbiology currently recommend serologic testing or polymerase chain reaction (PCR) for the diagnosis of C pneumoniae. Despite evident drawbacks, serology is still considered the gold standard, but this is likely to change.

Culture for C pneumoniae is technically complex and time consuming. When compared to serology and PCR, it also has low sensitivity and is mainly used in research labs.

The preferred serologic test is microimmunofluorescence (MIF). This is more sensitive and specific than complement fixation (CF), although cross reactivity with other chlamydiae species may still occur.

Criteria for infection include a single IgM titer ≥1:16 or a 4-fold increase in IgG titer. The absence of detectable titers a few weeks after symptom onset does not exclude the diagnosis because antibodies may take several weeks to appear (2-3 weeks for IgM and 6-8 weeks for IgG). In reinfections, IgM may be absent or low, and IgG may appear within 2 weeks. A single elevation in IgG titer may not be reliable, because elderly patients can have persistently elevated IgG titers due to repeated infections.

Enzyme-linked immunosorbent assay is another serologic test available but has not been validated due to cross reactivity and variations in specificity depending on the antigen used.

Overall, serologic testing is poorly standardized and studies have shown poor reproducibility. It should be interpreted carefully with attention to the course of illness.

Real-time PCR assays of pharyngeal swab, bronchoalveolar lavage, sputum or tissue can be used to detect C pneumoniae-specific DNA. Because of the complexity of these tests, widespread implementation had been limited until recent years.

The FilmArray Respiratory Panel is a multiplex PCR which detects common respiratory pathogens in nasopharyngeal specimens. In 2012, the US Food and Drug Administration (FDA) approved the addition of 2 corona viruses and 3 bacteria to the Panel, including C pneumoniae, Bordetella pertussis, and Mycoplasma pneumonia.The FilmArray Panel can now detect 17 viruses and 3 bacteria from a single sample.
 Reported sensitivity and specificity were both 100% for C pneumoniae but the sample size was small and fewer than 10 samples were positive in the study.

Studies comparing PCR to MIF IgM during outbreaks of C pneumoniae have shown comparable sensitivity (68-71% vs. 60-79%) and higher specificity (93-97% vs 77-86%). Overall data suggests molecular testing may be a more useful diagnostic tool in this setting.

Widespread use of molecular testing in the future may increase reliable data on presentation and epidemiology of C pneumoniae pneumonia.

The white blood cell count is usually not elevated in C pneumoniae infection. Alkaline phosphate levels may be elevated.

Chest Radiography

Chest radiographs of patients with C pneumoniae pneumonia most commonly show a single subsegmental infiltrate that is mainly located in the lower lobes. Extensive consolidation is rare, although acute respiratory distress syndrome (ARDS) has been reported. No radiographic findings are characteristic. Residual changes can be observed even after 3 months. Pleural effusion occurs in 20-25% of cases.

Management of C pneumoniae Pneumonia

Administer empiric treatment when mixed infections with other organisms are present (eg, pneumococci, mycoplasma, legionella). The frequency of mixed infection can be as high as 60%. Clinicians must treat empirically, because rapid testing for atypical pathogens is not readily available, and antibiotic therapy is usually completed before the results of serology testing become available.

Severely ill hypoxemic patients may require ventilatory support in an intensive care unit.

Drug of choice

Macrolides are the first-line antibiotics for the treatment of C pneumoniae pneumonia. Newer macrolides such as azithromycin (500 mg PO/IV once daily) and clarithromycin (1 g PO once daily [clarithromycin XL] or 500 mg PO twice daily) are better tolerated than erythromycin (250-500mg PO 4 times a day).

Treatment should be continued for at least 10-14 days after defervescence. If symptoms persist, a second course with a different class of antibiotics is usually effective.

Alternative drugs

Doxycycline (100 mg PO twice daily for 10-14 days) was once the treatment of choice. It is still a favored agent but should be avoided in children younger than 9 years and in pregnant women. Tetracycline hydrochloride (500 mg PO 4 time a day) is also active in vitro.

Fluoroquinolones, including levofloxacin (500 mg PO/IV once daily for 10-14 days or 750 mg PO/IV once daily for 5 days) and moxifloxacin (400 mg PO/IV once daily for 10-14 days) are also alternative options.  Studies investigating the efficacy of erythromycin, clarithromycin, azithromycin, levofloxacin, and moxifloxacin have shown similar results (70-86%) for the eradication of the organism from the nasopharynx.

Telithromycin is the first ketolide antibiotic approved for the treatment of C pneumoniae by US FDA in 2007. This agent is more expensive than doxycycline. Telithromycin is a potent inhibitor of CYP3A4 and can cause potentially dangerous increases in serum concentrations of simvastatin, lovastatin, atorvastatin, midazolam, and other drugs. If this agent is used, statins should be withheld for the duration of therapy. Hepatotoxicity (some fatal cases) has been reported in about 1/1,000,000. Telithromycin is contraindicated in patients with 
myasthenia gravis.

Patient education and consultations

Educate patients about the possible need for retreatment in case of a protracted course or recurrence.

Consultations with an infectious disease and/or a pulmonary specialist may be required if a patient requires hospitalization or does not respond to therapy.

Surgical Care

Aortic valve replacement may be required for patients with endocarditis

Mycoplasma Pneumonia

Mycoplasma pneumonia (MP) is a contagious respiratory infection. The disease spreads easily through contact with respiratory fluids, and it causes regular epidemics.

Symptoms

Common symptoms of MP include:

persistent fever

dry cough

malaise

fever

In rare cases, the infection may become dangerous and cause damage to the heart or central nervous system. Examples of these disorders include:

arthritis, which is a disorder in which the joints become inflamed

pericarditis, which is inflammation of the pericardium that surrounds the heart

Guillain-Barré syndrome, which is a neurological disorder that can lead to paralysis and death

encephalitis, which is an inflammation of the brain

Diagnosis

The disease generally develops silently for the first one to three weeks after exposure. Diagnosis is difficult in the early stages because the body doesn’t instantly reveal an infection. Sometimes manifestations of infection may occur outside of your lung. If this happens, signs of infection may include the breakup of red blood cells, a skin rash, and joint involvement. The symptoms and signs can indicate infection of the gastrointestinal tract, central nervous system, and heart disease. Three to seven days after the first symptoms appear, medical testing can show evidence of an MP infection.

Treatment

Antibiotics

The first line of treatment for MP is antibiotics. Children get different antibiotics than adults to avoid any potentially dangerous side effects.

Macrolides, the first choice of antibiotics for children, include:

erythromycin

clarithromycin

roxithromycin

azithromycin

Antibiotics prescribed for adults include:

doxycycline

tetracycline

quinolones

Corticosteroids

Not all people respond to antibiotic treatment. Alternative treatments include the following corticosteroids:

prednisolone

methylprednisone

Immunomodulatory Therapy

If you have a severe case of MP, you may need antibiotics and a treatment called

“immunomodulatory therapy.” This type of therapy can boost or decrease the effects of other medicines. Examples of immunomodulatory medications that are used with antibiotics include:

corticosteroids

intravenous Ig (IVIg)

In order to make a diagnosis, your doctor will listen to your breathing with a stethoscope for any abnormal sounds. A chest X-ray and a CT scan may also help your doctor to make a diagnosis

Legionella

Legionnaires’ disease is a severe type of pneumonia, or lung infection. Bacteria called Legionella cause this infection. The bacteria were discovered after an outbreak at a Philadelphia convention of the American Legion in 1976. Those who were affected developed a form of pneumonia that eventually became known as Legionnaires’ disease

Legionella may also cause a more mild condition referred to as Pontiac fever. Pontiac fever doesn’t cause pneumonia and isn’t life-threatening. It has symptoms similar to those of a mild flu, and it usually goes away on its own. Pontiac fever and Legionnaire’s disease are sometimes collectively called Legionellosis

Cause

Bacteria called Legionella cause Legionnaires’ disease. The bacteria invade the lungs and cause an infection known as pneumonia.

Legionella usually live in warm freshwater. Common locations include:

hot tubs

whirlpool spas

swimming pools

cooling systems or air-conditioning units for large buildings, such as hospitals

public showers

humidifiers

fountains

natural bodies of water, such as lakes, rivers, and creeks

The bacteria can survive outdoors, but they’re known to multiply rapidly in indoor water systems. People get infected by inhaling water droplets or mist in the air that’s contaminated with the bacteria. The disease can’t be spread directly from person-to-person.

Legionella bacteria usually thrive in warm water. People become infected with Legionella by breathing in contaminated droplets of water in the air. Outbreaks have been linked to water systems in hospital buildings and to whirlpool spas in hotels and cruise ships

Legionnaires’ disease will usually start causing symptoms within two to 14 days after exposure to the bacteria. This period is called the incubation period. The symptoms are similar to those of other types of lung infections.

Symptoms

The most common symptoms include:

a fever above 104°F

chills

a cough, with or without mucus or blood

Other symptoms may include:

headaches

muscle aches

a loss of appetite

chest pain

fatigue

Diagnosis

Your doctor can diagnose Legionnaires’ disease by testing your blood or urine for the presence of Legionella antigens. Antigens are substances that your body recognizes as harmful. Your body produces an immune response to antigens to fight infection. Your doctor may also test a sample of sputum, or phlegm, for the Legionella bacteria.

Your doctor might also perform a chest X-ray. While the X-ray can’t be used to confirm Legionnaires’ disease, it can help determine the severity of your lung infection

Treatment

Legionnaires’ disease is always treated with antibiotics. Treatment is usually started as soon as the disease is suspected, without waiting for confirmation. Prompt treatment significantly lowers the risk of complications.

Many people completely recover with treatment, but most will need care in the hospital. Elderly people and those with other health conditions are particularly vulnerable to the effects of Legionnaires’ disease. While in the hospital, they may receive oxygen or other breathing support. They may also be given fluids and electrolytes through a vein in their arm (IV) to prevent dehydration.

6.  Treatment of pneumonia. Principles of antibiotic therapy

Treatment of pneumonia

The type of treatment prescribed for pneumonia mostly depends on what type of pneumonia is present, as well as how severe it is. In many cases, pneumonia can be treated at home.

General Treatment

The typical treatment plan for pneumonia includes taking all prescribed medications and participating in follow-up care. A chest X-ray may be ordered to make sure your pneumonia has been successfully treated.

Treating Bacterial Pneumonia

Organism		First-Line Antimicrobials	Alternative Antimicrobials
Streptococcus pneumoniae
	Penicillin susceptible (MIC < 2 mcg/mL)	Penicillin G, amoxicillin	Macrolide, cephalosporin (oral or parenteral), clindamycin, doxycycline, respiratory fluoroquinolone
	Penicillin resistant (MIC ≥2 mcg/mL)	Agents chosen on the basis of sensitivity	Vancomycin, linezolid, high-dose amoxicillin (3 g/d with MIC ≤4 mcg/mL
Staphylococcus aureus
	Methicillin susceptible	Antistaphylococcal penicillin	Cefazolin, clindamycin
	Methicillin resistant	Vancomycin, linezolid	Trimethoprim- sulfamethoxazole
Haemophilus influenza
	Non–beta-lactamase producing	Amoxicillin	Fluoroquinolone, doxycycline, azithromycin, clarithromycin
	Beta-lactamase producing	Second- or third-generation cephalosporin, amoxicillin/clavulanate	Fluoroquinolone, doxycycline, azithromycin, clarithromycin
Mycoplasma pneumoniae		Macrolide, tetracycline	Fluoroquinolone
Chlamydophila pneumoniae		Macrolide, tetracycline	Fluoroquinolone
Legionella species		Fluoroquinolone, azithromycin	Doxycycline
Chlamydophila psittaci		Tetracycline	Macrolide
Coxiella burnetii		Tetracycline	Macrolide
Francisella tularensis		Doxycycline	Gentamicin, streptomycin
Yersinia pestis		Streptomycin, gentamicin	Doxycycline, fluoroquinolone
Bacillus anthracis(inhalational)		Ciprofloxacin, levofloxacin, doxycycline	Other fluoroquinolones, beta-lactam (if susceptible), rifampin, clindamycin, chloramphenicol
Enterobacteriaceae		Third-generation cephalosporin, carbapenem	Beta-lactam/beta-lactamase inhibitor, fluoroquinolone
Pseudomonas aeruginosa		Antipseudomonal beta-lactam plus ciprofloxacin, levofloxacin, or aminoglycoside	Aminoglycoside plus ciprofloxacin or levofloxacin
Bordetella pertussis		Macrolide	Trimethoprim- sulfamethoxazole
Anaerobe (aspiration)		Beta-lactam/beta-lactamase inhibitor, clindamycin	Carbapenem
MIC = Minimal inhibitory concentration.

Treating Viral Pneumonia

Virus	Treatment	Prevention
Influenza virus	Oseltamivir Peramivir Zanamivir	Influenza vaccine Chemoprophylaxis with: Zanamivir Oseltamivir
Respiratory syncytial virus	Ribavirin	RSV immunoglobulin Palivizumab
Parainfluenza virus	Ribavirin
Herpes simplex virus	Acyclovir
Varicella-zoster virus	Acyclovir	Varicella-zoster immunoglobulin
Adenovirus	Ribavirin
Measles virus	Ribavirin	Intravenous immunoglobulin
Cytomegalovirus	Ganciclovir Foscarnet	Intravenous immunoglobulin

Principles of antibiotic therapy

7.                Describe the complications of pneumonia. Make differential diagnosis of pneumonia.

Describe the complications of pneumonia

Bacteria in the bloodstream (bacteremia). Bacteria that enter the bloodstream from  lungs can spread the infection to other organs, potentially causing organ failure.

Lung abscess. An abscess occurs if pus forms in a cavity in the lung. An abscess is usually treated with antibiotics. Sometimes, surgery or drainage with a long needle or tube placed into the abscess is needed to remove the pus.

Fluid accumulation around lungs (pleural effusion). Pneumonia may cause fluid to build up in the thin space between layers of tissue that line the lungs and chest cavity (pleura). If the fluid becomes infected, may need to have it drained through a chest tube or removed with surgery.

Difficulty breathing. If pneumonia is severe or patient have chronic underlying lung diseases, may have trouble breathing in enough oxygen. may need to be hospitalized and use a breathing machine (ventilator) while your lung heals.

Make differential diagnosis of pneumonia

Several diseases can present with similar signs and symptoms to pneumonia, such as: chronic obstructive pulmonary disease (COPD), asthma, pulmonary edema, bronchiectasis, lung cancer, and pulmonary emboli. Unlike pneumonia, asthma and COPD typically present with wheezing, pulmonary edema presents with an abnormal electrocardiogram, cancer and bronchiectasis present with a cough of longer duration, and pulmonary emboli presents with acute onset sharp chest pain and shortness of breath.

8.  Clinical features of fibrinous and exudative pleurisy. Differential diagnosis of exudates from transudates. Laboratory investigations of effusion.

Clinical features of fibrinous and exudative pleurisy

Fibrinous

Clinical features

Complaints are sharp chest pain with breathing, shortness of breath,

cough, fever, poor appetite. The most common symptom of dry pleurisy is

pleuritic chest pain, which may begin suddenly. Typically, pleuritic pain

is a stabbing sensation aggravated by breathing and coughing, but it can

vary in character. The pain varies from vague discomfort to an intense

stabbing pain. It may be felt only when the person breathes deeply or

coughs, or it may be felt continuously but may be worsened by deep

breathing and coughing.


 The visceral pleura is insensitive; pain results

from inflammation of the parietal pleura, which is mainly innervated by

intercostal nerves. Pain is usually felt over the pleuritic site but may be

referred to distant regions. Irritation of posterior and peripheral portions of

the diaphragmatic pleura, which are supplied by the lower six intercostal

nerves, may cause pain to be felt over the lower chest wall or abdomen and

may simulate intra-abdominal disease. 

Irritation of the central portion of

the diaphragmatic pleura, innervated by the phrenic nerves, causes pain to

be felt over the neck and shoulder. Breathing may be rapid and shallow

because deep breathing induces pain; the muscles on the painful side move

less than those on the other side. Cough is typically dry, nonproductive.

Usually patient may have subfebrile temperature

Exudative

Clinical features

Complains. The most commonly associated symptoms are

progressive dyspnea, cough (typically nonproductive), and chest pain.

Dyspnea is present as the most common clinical symptom. It

indicates a large effusion (usually not <500 mL). A large effusion may

produce or contribute to dyspnea through diminished lung volume,

especially if there is underlying pulmonary disease, mediastinal shift to the

contralateral side, and diminished function and recruitment of inspiratory

muscles due to an expanded thoracic cage.

Chest pain may be mild or severe, has a dull character. It often

diminishes in intensity as the pleural effusion increases in size. Chest pain

signifies pleural irritation, which can aid in the diagnosis of the cause of

the effusion, since most transudative effusions do not cause direct pleural

irritation. Other signs and symptoms occurring with pleural effusions are

associated more closely with the underlying disease process.

Usually patient may have subfebrile temperature. However, it may

become moderate and high grade, when pleurisy becomes purulent. In this

case, patient will also have chills, sweats, weight loss, poor appetite

Differential diagnosis of exudates from transudates

Transudate vs. exudate  ·         view ·         talk ·         edit
	Transudate	Exudate
Main causes	↑ hydrostatic pressure, ↓ colloid osmotic pressure	Inflammation-Increased Vascular Permeability
Appearance	Clear[1]	Cloudy[1]
Specific gravity	< 1.012	> 1.020
Protein content	< 2.5 g/dL	> 2.9 g/dL[2]
fluid protein/ serum protein	< 0.5	> 0.5[3]
SAAG = Serum [albumin] - Effusion [albumin]	> 1.2 g/dL	< 1.2 g/dL[4]
fluid LDH upper limit for serum	< 0.6 or < 2⁄3	> 0.6[2] or > 2⁄3[3]
Cholesterol content	< 45 mg/dL	> 45 mg/dL

Laboratory investigations of effusion

DRY (FIBRINOUS) PLEURISY

Blood test usually shows a slight leukocytosis and slightly increased ESR.

A chest x-ray examination does not give us a lot of information. We can find decrease diaphragmatic movements on the affected side.

EXUDATIVE (WET) PLEURISY

Blood test usually shows leukocytosis and increased ESR.

X-rays examination: A chest x-ray in the upright position and while

lying on the side is an accurate tool in diagnosing small amounts of fluid.

Blunting of costophrenic angle on posterior-anterior view suggests at least

500 ml of fluid. Larger effusions may show loss of diaphragm border.

Mediastinal shift is seen only in presence of massive effusions (usually

>1000 mL), which is noted on chest radiographs as displacement of the

trachea and mediastinum to the contralateral side of the pleural effusion.

Ultrasound is also a very sensitive method of detecting the presence

of fluid.

Pleural aspiration. Pleural aspiration is diagnostic as well as

therapeutic approach to relieve the dyspnea. Pleural aspiration is done

through intercostals space over the area of maximum dullness on

percussion or where maximum opacity on X-ray is seen. Usually it is 6th

intercostal space laterally or 8th intercostal space posteriorly. Fluid analysis

in some cases may help to define etiology of the effusion. Most fluid

should be sent for protein, LDH, glucose, gram stain and bacterial culture,

and pH. The fluid can also be tested for cells (neutrophils, TB and cancer

cells)

9.omplications of pleurisy. Treatment of pleurisy. Indications for surgical treatment.

Complications of pleurisy

Pleural effusion

In some cases of pleurisy, excess fluid builds up in the pleural space. This is called a pleural effusion. The buildup of fluid usually forces the two layers of the pleura apart so they don't rub against each other when breathing. This can relieve the pain of pleurisy. A large amount of extra fluid can push the pleura against the lung until the lung, or a part of it, collapses. This can make it hard to breathe.

In some cases of pleural effusion, the extra fluid gets infected and turns into an abscess. This is called an empyema.

Pleural effusion involving fibrinous exudates in the fluid may be called fibrinous pleurisy. It sometimes occurs as a later stage of pleurisy.

A person can develop a pleural effusion in the absence of pleurisy. For example, pneumonia, heart failure, cancer, or a pulmonary embolism can lead to a pleural effusion.

Pneumothorax

Air or gas also can build up in the pleural space. This is called a pneumothorax. It can result from acute lung injury or a lung disease like emphysema. Lung procedures, like surgery, drainage of fluid with a needle, examination of the lung from the inside with a light and a camera, or mechanical ventilation, also can cause a pneumothorax.

The most common symptom is sudden pain in one side of the lung and shortness of breath. A pneumothorax also can put pressure on the lung and cause it to collapse.

If the pneumothorax is small, it may go away on its own. If large, a chest tube is placed through the skin and chest wall into the pleural space to remove the air.

Hemothorax

Blood also can collect in the pleural space. This is called hemothorax. The most common cause is injury to the chest from blunt force or surgery on the heart or chest. Hemothorax also can occur in people with lung or pleural cancer.

Hemothorax can put pressure on the lung and force it to collapse. It also can cause shock, a state of hypoperfusion in which an insufficient amount of blood is able to reach the organs.

Treatment of pleurisy

Treatment has several goals:

Relief of symptoms

Removal of the fluid, air, or blood from the pleural space

Treatment of the underlying condition

Procedures[edit]

If large amounts of fluid, air, or blood are not removed from the pleural space, they may cause the lung to collapse.

The surgical procedures used to drain fluid, air, or blood from the pleural space are as follows:

During thoracentesis, a needle or a thin, hollow, plastic tube is inserted through the ribs in the back of the chest into the chest wall. A syringe is attached to draw fluid out of the chest. This procedure can remove more than 6 cups (1.5 litres) of fluid at a time.

When larger amounts of fluid must be removed, a chest tube may be inserted through the chest wall. The doctor injects a local painkiller into the area of the chest wall outside where the fluid is. A plastic tube is then inserted into the chest between two ribs. The tube is connected to a box that suctions the fluid out. A chest x-ray is taken to check the tube's position.

A chest tube is also used to drain blood and air from the pleural space. This can take several days. The tube is left in place, and the patient usually stays in the hospital during this time.

Sometimes the fluid contains thick pus or blood clots, or it may have formed a hard skin or peel. This makes it harder to drain the fluid. To help break up the pus or blood clots, the doctor may use the chest tube to put certain medicines into the pleural space. These medicines are called fibrinolytics. If the pus or blood clots still do not drain out, surgery may be necessary.

Medications[edit]

A couple of medications are used to relieve pleurisy symptoms:

Paracetamol (acetaminophen) or anti-inflammatory agents to control pain and decrease inflammation. Only indomethacin (brand name Indocin) has been studied with respect to relief of pleurisy.[15]

Codeine-based cough syrups to control the cough

There may be a role for the use of corticosteroids (for tuberculous pleurisy), tacrolimus (Prograf) and methotrexate (Trexall, Rheumatrex) in the treatment of pleurisy. Further studies are needed.

Lifestyle changes[edit]

The following may be helpful in the management of pleurisy:

Lying on the painful side may be more comfortable

Breathing deeply and coughing to clear mucus as the pain eases. Otherwise, pneumonia may develop.

Getting rest

Treating the cause[edit]

Ideally, the treatment of pleurisy is aimed at eliminating the underlying cause of the disease.

If the pleural fluid is infected, treatment involves antibiotics and draining the fluid. If the infection is tuberculosis or from a fungus, treatment involves long-term use of antibiotics or antifungal medicines.

If the fluid is caused by tumors of the pleura, it may build up again quickly after it is drained. Sometimes anti-tumor medicines will prevent further fluid buildup. If they don't, the doctor may seal the pleural space. This is called pleurodesis. Pleurodesis involves the drainage of all the fluid out of the chest through a chest tube. A substance is inserted through the chest tube into the pleural space. This substance irritates the surface of the pleura. This causes the two layers of the pleura to squeeze shut so there is no room for more fluid to build up.

Chemotherapy or radiation treatment also may be used to reduce the size of the tumors.

If congestive heart failure is causing the fluid buildup, treatment usually includes diuretics and other medicines.

The treatment for pleurisy depends on its origin and is prescribed by a physician on a base of an individual assessment.[16] Paracetamol (acetaminophen) and amoxicillin, or other antibiotics in case of bacterial infections, are common remedies dispensed by doctors to relieve the initial symptoms and pain in the chest, while viral infections are self-limited. Non-steroidal anti-inflammatory drugs (NSAIDs), preferably indometacin, are usually employed as pain control agents.[10]

Alternative treatments[edit]

A number of alternative or complementary medicines are being investigated for their anti-inflammatory properties, and their use in pleurisy. At this time, clinical trials of these compounds have not been performed.

Extracts from the Brazilian folk remedy Wilbrandia ebracteata ("Taiuia") have been shown to reduce inflammation in the pleural cavity of mice.[17][18] The extract is thought to inhibit the same enzyme, cyclooxygenase-2 (COX-2), as the non-steroidal anti-inflammatory drugs.[18] Similarly, an extract from the roots of the Brazilian Petiveria alliacea plant reduced inflammation in a rat model of pleurisy.[19] The extract also reduced pain sensations in the rats. An aqueous extract from Solidago chilensis has been shown to reduce inflammation in a mouse model of pleurisy.[20]

Pleurisy root Asclepias tuberosa is another example of a herbal solution for this inflammation

10.           Etiology and pathogenesis of acute bronchitis.

Acute bronchitis is one of the most

common medical conditions seen in a doctor's office. It is primarily caused

by a virus that infects the respiratory system. There are a number of

different respiratory viruses that can cause it, including influenzavirus

types A and B, rhinovirus, parainfluenza and coronavirus.

 Viral infection may create an environment in which bacterial infection also can develop.

Bacterial infection with Mycoplasma pneumoniae, Clamydia pneumoniae,

and Bordetella pertussis (whooping cough), particulary in young adults,

can lead to acute bronchitis. Infection causes the mucous membrane of the

bronchial tubes to become inflamed and produce thick, sticky mucus. 

The overproduction of mucus reduces the normal defensive function (called

clearing function) of the cilia. Inflammation and accumulated mucus

narrow the airways, restrict respiration, and promote bacterial infection.

One more cause of acute bronchitis may be air pollutants and exposure to

chemicals, fumes, and dust

11.           Describe the symptoms of acute bronchitis. Principles of treatment.

Describe the symptoms of acute bronchitis

Clinical features

Complaints include the following: cough, “rattle" sensation in chest,

malaise, slight fever (37-38°C), sore throat, poor sleep. Cough stays steady

or gets increasingly worse for 10 days to 2 weeks. Usually it starts out dry

and irritating, but appears with sputum production over time. Sputum may

be thin, clear, and white due to viral infection and thick, pus-filled, yellow

due to bacterial infection.

Physical examination. The general inspection does not reveal any

specific signs. State of the patient may be satisfactory. Palpation and

percussion of the chest. Palpation and percussion of the chest do not reveal

any abnormalities. Auscultation of the lungs. During auscultation you may

hear harsh breathing, diffuse high-pitched wheezes or rhonchi. Symptoms

of the disease last for 10-12 days. Outcome of the disease usually is

recovery of the patient

Principles of treatment

Over-the-counter non-steroidal anti-inflammatory drugs (NSAIDS) such as aspirin, ibuprofen and naproxen may soothe your sore throat.

Humidifiers create moisture in the air you breathe. This can help loosen mucus in your nasal passages and chest, making it easier to breathe.

Drinking plenty of liquids, such as water or tea, can help thin out mucus. This makes it easier to cough it up or blow it out through your nose

12.           Etiology and pathogenesis of chronic bronchitis. Differential diagnosis.

Etiology

Tobacco smoke, air pollution, infections are the most

important etiologic agents of chronic bronchitis. The most important

environmental etiologic agent is chronic inhalation of tobacco smoke.

Smoking stimulates inflammatory cytokines and depresses alveolar

macrophages, reduces the functional integrity of pulmonary surfactant,

retards mucus transport, enhances the release of lysosomal enzymes. Over

90% of patients with chronic bronchitis have a smoking history. 


Air pollution such as dust, smoke, fumes also may cause chronic bronchitis.

Bronchitis may be caused by viruses and bacteria. Viral infections in

childhood may predispose patients to COPD in adulthood. Viral and

bacterial infections are involved in acute exacerbation of chronic

bronchitis.

Pathogenesis

The airflow obstruction in chronic bronchitis is caused

by excessive mucus production, edema of mucosal layer and smooth

muscles contraction.

When the cells of the bronchial-lining tissue are irritated, the cilia,

which normally trap and eliminate pollutants, stop functioning.

Consequently, the air passages become clogged by debris and irritation

increases. In response, a heavy secretion of mucus develops, which causes

the characteristic cough of bronchitis. There is less efficient clearance of

the increased mucous, because clearance of mucous is mediated by ciliated

cells which have been reduced. Moreover, mucosal edema and permanent

structural damage of the airway wall reduce the caliber of the air passages.

Air is trapped in the alveoli because the degree of obstruction is greater

during expiration, which leads to over-inflation of the alveoli resulting in

alveolar septa destruction (emphysema).

Differential diagnosis

·         Acute bronchitis

·         AIDS-related complex

·         Asthma

·         Bronchiectasis

·         Emphysema

·         Lung cancer

·         Pharyngitis

·         Pneumonia

·         Sinusitis

·         Tonsillitis

·         Tuberculosis

13.           Clinical picture of chronic bronchitis. Instrumental and laboratory methods of investigations for establish the diagnosis. Principles of treatment.

 Clinical picture of chronic bronchitis

Clinical features

Complaints: cough with sputum production, shortness of breath

aggravated by exertion or mild activity, wheezing, fever, and soreness in

the chest, fatigue.

Initially, it begins as a "smoker’s cough" – the expectoration of small

amounts of phlegm each morning. It is usually worse in winter time and

when the person has a cold. In these early phases of chronic bronchitis, the

person may lead an entirely normal life, including vigorous sports.

Sensitive breathing tests, however, can indicate the beginning of

irreversible damage to the lungs even at this stage.

The cough becomes more frequent during the day time and even at

night with disturbing sleep. The patient then notices that activities

previously tolerated well, cause shortness of breath and perhaps some

wheezing also appear. As the disease progresses, shortness of breath may

be caused by very ordinary activities such as getting dressed in the

morning or having a bath.

The patient with advanced bronchitis may be unable to walk or climb

stairs without supplemental oxygen. He or she may be confined to a chair

or bed because of shortness of breath and type of heart failure which may

develop in the late stages of this disease. Minor chest infections in patients

with severe chronic bronchitis may require intensive treatment in hospital.

Physical examination. The general inspection reveals central

cyanosis in patients with chronic bronchitis. Later patient may have

peripheral edemas. Patient may have barrel-shape chest. The anteriorposterior

diameter of the chest increases. The rib interspaces become wide.

There are the signs of overinflation of the chest. Patient may use of

accessory respiratory muscles of respiration. You can note intercostal

retractions (in-drawing of the skin between ribs and above the sternum and

clavicles). Patients may have tachypnea. Palpation of the chest. Elasticity

of the chest is decreased. Tactile fremitus is symmetrically decreased in

the case of emphysema. Percussion of the chest. Percussion gives

hyperresonance over the lungs. The inferior border of the lungs may

become lower. You can find the poor diaphragmatic excursion.

Auscultation of the lungs. During auscultation you may hear harsh

breathing due to airways obstruction, diffuse high-pitched wheezes and

rhonchi. Auscultation may gives us decreased vesicular breath sounds due

to emphysema of lungs. Cardiovascular system. Patients have right

ventricular hypertrophy

Instrumental and laboratory methods of investigations for establish the diagnosis

Sputum examination: Sputum may appear mucous or purulent, in a

moderate quantity, with increased leucocytes and ciliary epithelial cells

content.

Blood test: Blood test indicates a moderate leukocytosis and

increased erythrocyte sedimentation rate (ESR). Increased erythrocytes

and hemoglobin levels appear due to chronic respiratory failure.

Spirometry: A spirometry reveals obstructive lung disease. Forced

expiratory volume in one second (FEV1) is reduced. The ratio of FEV1 to

vital capacity (VC) is also decreased. The FEV1/FVC ratio less than 70%

defines obstructive airway disease. An FEV1/FVC ratio of less than 50%

indicates end-stage of obstructive airway disease.

Chest radiography: Radiographic findings correlate poorly with

symptoms in most patients with chronic bronchitis. Common, but

nonspecific, findings include hyperinflation, diaphragmatic flattening and

peribronchial markings, “dirty” lung fields.

Arterial blood gas measurement: Advanced stage emphysema may

require an arterial blood gas test. This test measures the amount of oxygen

and carbon dioxide present in the blood. Hypercapnia with acidosis is

suggestive of acute decompensation. A high CO2 level with a normal pH is

suggestive of a compensated chronic state.

ECG may show tachycardia and "P" pulmonale or atrial flutter, signs

of right ventricular hypertrophy.

Principles of treatment

-Reducing exposure to noxious particles and gases

-Bronchodilators

Bronchodilator therapy is central to the management of

breathlessness. The inhaled route is preferred and a

number of different agents, delivered by a variety of

devices, are available. 

Choice should be informed by patient preference and inhaler assessment. Short-acting

bronchodilators, such as the β2-agonists salbutamol and

terbutaline, or the anticholinergic ipratropium bromide,

may be used for patients with mild disease, but longeracting

bronchodilators, such as the β2-agonists salmeterol,

formoterol and indacaterol, or the anticholinergic

tiotropium bromide, are more appropriate for patients

with moderate to severe disease. Significant improvements

in breathlessness may be reported, despite

minimal changes in FEV1, probably reflecting improvements

in lung emptying that reduce dynamic hyperinflation

and ease the work of breathing.

-Corticosteroids

Inhaled corticosteroids (ICS) reduce the frequency

and severity of exacerbations, and are currently

recommended

in patients with severe disease (FEV1

< 50%) who report two or more exacerbations requiring

antibiotics or oral steroids per year. Regular use is associated

with a small improvement in FEV1, but ICS do

not alter the natural history of the FEV1 decline. It is

more usual to prescribe a fixed combination of an ICS

and a LABA.

Oral corticosteroids are useful during exacerbations

but maintenance therapy contributes to osteoporosis

and impaired skeletal muscle function and should be

avoided. Oral corticosteroid trials assist in the diagnosis

of asthma but do not predict response to inhaled steroids

in COPD.

-Pulmonary rehabilitation

Exercise should be encouraged at all stages and patients

reassured that breathlessness, whilst distressing, is not

dangerous. Multidisciplinary programmes that incorporate

physical training, disease education and nutritional

counselling reduce symptoms, improve health status

and enhance confidence. Most programmes include

2–3 sessions per week for 6 and 12 weeks, and are

accompanied by demonstrable and sustained improvements

in exercise tolerance and health status.

-Oxygen therapy

14.           Chronic obstructive pulmonary disease (COPD): etiology, pathogenesis, risk factors for development of COPD.

Etiology

Long-term exposure to lung irritants that damage the lungs and the airways usually is the cause of COPD. In the United States, the most common irritant that causes COPD is cigarette smoke. Pipe, cigar, and other types of tobacco smoke also can cause COPD, especially if the smoke is inhaled.

Pathogenesis

COPD has both pulmonary and systemic components. The presence of airflow limitation, combined with premature airway closure, leads to gas trapping and hyperinflation, reducing pulmonary and chest wall compliance. Pulmonary hyperinflation also flattens the diaphragmatic muscles and leads to an increasingly horizontal alignment of the intercostal muscles, placing the respiratory muscles at a mechanical disadvantage. 

The work of breathing is therefore  markedly increased, first on exercise, when the time for expiration is further shortened, but then, as the disease advances, at rest.

Emphysema may be classified by the pattern of the enlarged airspaces as centriacinar, panacinar or paraseptal. Bullae form in some individuals. This results in impaired gas exchange and respiratory failure

Risk factors for development of COPD

Environmental

• Tobacco smoke accounts for 95% of cases in UK

• Indoor air pollution; cooking with biomass fuels in confined

areas in developing countries

• Occupational exposures, such as coal dust, silica and

cadmium

• Low birth weight may reduce maximally attained lung

function in young adult life

• Lung growth: childhood infections or maternal smoking may

affect growth of lung during childhood, resulting in a lower

maximally attained lung function in adult life

• Infections: recurrent infection may accelerate decline in FEV1;

persistence of adenovirus in lung tissue may alter local

inflammatory response, predisposing to lung damage; HIV

infection is associated with emphysema

• Low socioeconomic status

• Cannabis smoking

Host factors

• Genetic factors: α1-antiproteinase deficiency; other COPD

susceptibility genes are likely to be identified

• Airway hyper-reactivity

15.           Classification of chronic obstructive pulmonary disease (COPD). Instrumental and laboratory methods of diagnostics.

Classification of chronic obstructive pulmonary disease (COPD)

Two classic types of COPD exist and are given various names.

Patients with “emphysematous”, “dyspneic” or “type A” COPD are

referred to as pink puffers. Those with “bronchitic”, “tussive” or “type B”

COPD are referred to as blue bloaters.

Pink puffers have predominant emphysema and shows symptoms at

relatively advanced age (often > 60 years). There is progressive exertional

dyspnea, weight loss and little or no cough and expectoration.
 Pulmonary function testing indicates mild hypoxia, hypocapnea (low PaCO2),

decreased DLCO and only a mild increase in Raw. These patients are not

cyanosed but are breathless, hence the term “pink puffer”.

Blue bloaters have predominant chronic bronchitis and at a

relatively young age experience chronic cough and expectoration, episodic

dyspnea and weight gain. Wheezing and rhonchi frequently are heard in

the chest and cor pulmonale often develops, accompanied by edema and

cyanosis. Pulmonary function testing indicates severe hypoxia,

hypercapnea, polycythemia, increased Raw and relatively preserved lung

volumes and DLCO. The combination of the edema and cyanosis accounts

for the term “blue bloater”.

Modified MRC dyspnoea scale

Grade Degree of breathlessness related to activities

0 No breathlessness, except with strenuous exercise

1 Breathlessness when hurrying on the level or

walking up a slight hill

2 Walks slower than contemporaries on level ground

because of breathlessness or has to stop for breath

when walking at own pace

3 Stops for breath after walking about 100 m or after

a few minutes on level ground

4 Too breathless to leave the house, or breathless

when dressing or undressing

(MRC = Medical Research Council)

Spirometric classification of COPD severity

based on post-bronchodilator FEV1

Based on NICE guidelines 2010

Stage Severity FEV1

I Mild* FEV1/FVC < 0.70

           FEV1 ≥ 80% predicted

II Moderate FEV1/FVC < 0.70

                   FEV1 50–79% predicted

III Severe FEV1/FVC < 0.70

                FEV1 30–49% predicted

IV Very severe FEV1/FVC < 0.70

                        FEV1 < 30% predicted or FEV1 < 50% predicted if respiratory failure present

*Mild COPD should not be diagnosed on lung function alone if the patient is

asymptomatic.

Instrumental and laboratory methods of diagnostics

Although there are no reliable radiographic signs that

correlate with the severity of airflow limitation, a chest

X-ray is essential to identify alternative diagnoses, such

as cardiac failure, other complications of smoking such

as lung cancer, and the presence of bullae.

 A blood count is useful to exclude anaemia or polycythaemia, and in

younger patients with predominantly basal emphysema,

α1-antiproteinase should be assayed.

The diagnosis requires objective demonstration of

airflow obstruction by spirometry and is established

when the post-bronchodilator FEV1/FVC is less than

70%. The severity of COPD may be defined in relation

to the post-bronchodilator FEV1 A low peak

flow is consistent with COPD but is non-specific, does

not discriminate between obstructive and restrictive disorders,

and may underestimate the severity of airflow

limitation.

Measurement of lung volumes provides an assessment

of hyperinflation. This is generally performed by

using the helium dilution technique; in patients

with severe COPD, and with large bullae in particular,

body plethysmography is preferred because the use of

helium may underestimate lung volumes. Emphysema

is suggested by a low gas transfer value.

 Exercise tests provide an objective assessment of exercise tolerance

and a baseline for judging response to bronchodilator

therapy or rehabilitation programmes; they may also

be valuable when assessing prognosis. Pulse oximetry

of less than 93% may indicate the need for referral for a

domiciliary oxygen assessment.

The assessment of health status provides valuable

clinical information. The St George’s Respiratory Questionnaire

(SGRQ) is a commonly used research tool but

is too cumbersome for routine clinical practice. The

COPD Assessment Test (CAT) employs only eight questions

and the scores correlate closely with the SGRQ.

HRCT is likely to play an increasing role in the assessment

of COPD, as it allows the detection, characterisation

and quantification of emphysema and is

more sensitive than a chest X-ray for detecting bullae

16.           Treatment of chronic obstructive pulmonary disease (COPD).

-Reducing exposure to noxious particles and gases

-Bronchodilators

Bronchodilator therapy is central to the management of

breathlessness. The inhaled route is preferred and a

number of different agents, delivered by a variety of

devices, are available.

 Choice should be informed by patient preference and inhaler assessment. Short-acting

bronchodilators, such as the β2-agonists salbutamol and

terbutaline, or the anticholinergic ipratropium bromide,

may be used for patients with mild disease, but longeracting

bronchodilators, such as the β2-agonists salmeterol,

formoterol and indacaterol, or the anticholinergic

tiotropium bromide, are more appropriate for patients

with moderate to severe disease. 

Significant improvements

in breathlessness may be reported, despite

minimal changes in FEV1, probably reflecting improvements

in lung emptying that reduce dynamic hyperinflation

and ease the work of breathing

-Corticosteroids

Inhaled corticosteroids (ICS) reduce the frequency

and severity of exacerbations, and are currently

recommended

in patients with severe disease (FEV1

< 50%) who report two or more exacerbations requiring

antibiotics or oral steroids per year. Regular use is associated

with a small improvement in FEV1, but ICS do

not alter the natural history of the FEV1 decline. It is

more usual to prescribe a fixed combination of an ICS

and a LABA.

Oral corticosteroids are useful during exacerbations

but maintenance therapy contributes to osteoporosis

and impaired skeletal muscle function and should be

avoided. Oral corticosteroid trials assist in the diagnosis

of asthma but do not predict response to inhaled steroids

in COPD.

-Pulmonary rehabilitation

Exercise should be encouraged at all stages and patients

reassured that breathlessness, whilst distressing, is not

dangerous. Multidisciplinary programmes that incorporate

physical training, disease education and nutritional

counselling reduce symptoms, improve health status

and enhance confidence. 

Most programmes include 2–3 sessions per week for 6 and 12 weeks, and are

accompanied by demonstrable and sustained improvements

in exercise tolerance and health status.

-Oxygen therapy

17.           Suppurative lung disease: definition, classification, triggers of suppurative lung disease.

 Definition

18.           Clinic and diagnosis of lung abscess, depending on the stage of the disease. Complications.

Clinic

Clinical features

Two periods are distinguished in the course of an abscess presence:

period before and after opening of the abscess cavity.

78

Data before abscess perforation

Complaints. Onset may be acute or insidious. The fever is of a

hectic (septic) type, with chill and night-sweats. If lung abscess appears as

complication of acute pneumonia temperature type may be remittent.

Patients have shortness of breath, breathing is frequent and shallow. Cough

on the first stage is dry.

 Patient may have chest pain, which increased in

deep breathing and in coughing. Such pain is present on the affected side

and usually indicates pleural involvement. Patients have poor appetite or

anorexia and weight loss, weakness and debility due to intoxication.

Physical examination. The state of the patient is severe. General

inspection. The respiration is rapid and difficult, the rate being usually

accelerated to some two or three times its normal amount (30-35 per

minute). Patient has forced position. He lies on the sick side, because such

position relieves the chest pain. The affected side of the chest lags behind

from the healthy one during the breathing. Palpation of the chest. 

Tactile fremitus is increased on the side with abscess. Percussion of lungs gives us

dullness or decreased resonance sound on the side of abscess. Auscultation

of the lungs. During auscultation we may find decreased vesicular breath

sounds or bronchial breath sounds in case of a large diameter of abscess. A

pleural friction rub may appear if abscess is situated superficially.

Data after abscess perforation

Complaints. When abscess perforates the bronchus, cough is present

with large amount of purulent sputum, putrid or not, which may be

expectorated over a few hours or several days. The expectorated sputum

characteristically is foul smelling and bad tasting, is purulent and may be

blood-streaked. Patient regains appetite.

Physical examination. The state of the patient improves after

opening of abscess and evacuation of its contents. The quantity of the

sputum increases with the patient change the position of the body. General

inspection. Patient has forced position. He lies on the sick side, because

such position decreases coughing. The affected side of the chest lags from

the healthy one during the breathing. Palpation of the chest. Tactile

fremitus increases on the side with abscess. Percussion may give us

tympanic sound if cavity will be of big size (more than 5 cm in diameter).

During auscultation we may find amphoric breath sounds in the case of big

cavity or quiet bronchial breath sounds in the case of small cavity.

Additionally loud, medium or large bubbling rales and rhonchi may be

Present.

Diagnosis

Blood test may reveal pronounced leukocytosis and a left shift,

anemia, markedly increased ESR.

Sputum analysis. Sputum is purulent and may be blood-streaked,

some times is putrid in a large amount. The sputum may contain necrotic

lung tissue, elastic fibers, big amount of leucocytes, alveolar cells.

A chest x-ray examination. A typical chest radiographic appearance

of a lung abscess is an irregularly shaped cavity with an air-fluid level

inside.

Complications

-Chronic lung abscess

- Empyema

- Pleural fibrosis

- Pulmonary haemorrhage

- Respiratory failure

- Pyopneumothorax

- Death

19.            Differential diagnosis of lung abscess with tuberculosis cavities, bronchiectasis, cavitary forms of lung cancer.

20.           Principles of treatment of lung abscess. Indications for surgical treatment.

Management

Supportive measures

Analgesia

Oxygen if required

Rehydration if indicated

Postural drainage with chest physiotherapy

Antibiotics

Most lung abscesses (80-90%) are now successfully treated with antibiotics.[6]

Begin with intravenous treatment, usually for about 2-3 weeks, and follow with oral antibiotics for a further 4-8 weeks.

Recommended first-line therapy includes beta-lactam/beta-lactamase inhibitor or cephalosporin (second- or third-generation) plus clindamycin.[3]

Previously, therapy with a broad-spectrum penicillin and clindamycin was used. Clindamycin had also been used alone (covers S. aureus and anaerobes and both oral and intravenous preparations exist); however, in the 1990s it was discovered that some anaerobes were resistant to both penicillin and clindamycin.

An alternative regimen is to begin with a broad-spectrum cephalosporin and flucloxacillin.[7]

Regimen should be altered once the organism is known.

Surgery

If the condition fails to resolve with conservative measures, bronchoscopy, CT-guided percutaneous drainage or cardiothoracic surgical intervention may be required.[8]

Surgery is associated with a number of complications, such as empyema and bronchoalveolar air leak - especially so in children.[7]

21.           Differential diagnosis of bronchial obstruction.

Pulmonary secretions

Foreign body

Bronchogenic carcinoma

Aspiration

Extrinsic compression by a mass

Metastatic tumour

Asthma

COPD

Emphysema

Bronchiectasis

Fibrosing alveolitis

Lung collapse

Lung fibrosis

Tracheomalacia

Tracheal stenosis

Bronchial stenosis

Endobronchial tumors

Enlarged lymph nodes

Tuberculosis

Histoplasmosis

Enlarged pulmonary arteries

Enlarged atrium from any causes

Bronchial oedema

22.           Clinic of acute and chronic right ventricular failure (pulmonary heart).

Pulmonary heart disease, also known as cor pulmonale is the enlargement and failure of the right ventricle of the heart as a response to increased vascular resistance (such as from pulmonic stenosis) or high blood pressure in the lungs

Clinics

Shortness of breath

Wheezing

Cyanosis

Ascites

Jaundice

Hepatomegaly

Raised jugular venous pressure (JVP)

Third heart sound

Intercostal recession

Presence of abnormal heart sounds

CARDIOLOGY

1.                Essential (primary) arterial hypertension. Etiology. Pathogenesis. Risk factors for development of hypertension and target organs

Etiology

The causes of this type are unknown but are likely to be a complex combination of genetic, environmental, and other factors

Pathogenesis

1) Increase of pressor factors.

- Abnormalities in the Renin-Angiotensin-Aldosterone System

- Inherited Abnormalities in the Sympathetic Nervous System.

- Increased release of neuropeptides (adrenaline, noradrenalin,

vasopressin, serotonin)

2) Decrease of depressor factors.

- The kallikrein system, which produces the potent vasodilator

bradykinin, is beginning to be studied. The decreased production of

prostaglandins, decreased activity of kallikrein system may lead to

hypertension.

- Low levels of Nitric Oxide. The gas nitric oxide can be

produced in the body, where it affects the smooth muscle cells that

line blood vessels; it helps keep them relaxed, flexible. It may also

help prevent blood clotting. Low levels of nitric oxide have been

observed in people with high blood pressure and may be an important

factor in essential hypertension.

- The decreased production of atrial natriuretic factor.

3) Metabolic mechanism of development of hypertension.

Combination of Insulin Resistance or Type 2 Diabetes with

obesity, hypercholesterolemia and hypertension is metabolic

syndrome. Hypertension in this syndrome has malignant character, is

resistant to treatment. People with metabolic syndrome have a

significantly greater chance for heart attack, kidney disease, and

stroke than those who have only high blood pressure.

Risk factors for development of hypertension

There are risk factors for high blood pressure that we can't

control. These are:

- Age. Your risk of high blood pressure increases as you get

older.

- Race. High blood pressure occurs far more frequently in blacks

than in any other racial group in the United States. High blood

pressure in blacks generally develops at an earlier age than it does in

whites. Plus, it's more likely to lead to serious complications such as

stroke or heart attack.

- Sex. In young adulthood and early middle age, high blood

pressure is more common in men than in women, but the opposite is

true for men and women of age 60 and older.

- Family history. High blood pressure tends to run in families.

The risk factors we can control or manage include:

- Obesity. The greater body mass you have, the more blood you

need to supply oxygen and nutrients to your tissues. The volume of

blood circulated through your blood vessels increases and creates

extra force on your artery walls. In addition, fat cells produce

chemicals that circulate and affect your blood vessels and heart.

- Inactivity. Lack of physical activity increases your risk of high

blood pressure by increasing your risk of being overweight. Inactive

people also tend to have higher heart rates. Their heart muscles have

to work harder with each contraction, increasing the force on the

arteries.

- Tobacco use. The chemicals in tobacco can damage the lining

of your artery walls, causing the arteries to accumulate fatty deposits

that contain cholesterol (plaques). Nicotine also constricts your blood

vessels and forces your heart to work harder.

- Sodium sensitivity and salt intake. People who are sodium

sensitive retain sodium more easily, leading to fluid retention and

increased blood pressure.

- Low potassium intake. Potassium is a mineral that helps

balance the amount of sodium in your cells. If you don't consume or

retain enough potassium, you can accumulate too much sodium.

- Excessive alcohol. Exactly how or why alcohol increases blood

pressure isn't understood. But over time, heavy drinking can damage

your heart muscle.

- Stress. High levels of stress can lead to a temporary but

dramatic increase in blood pressure. Stress also can promote high

blood pressure if you try to relax by eating more, using more nicotine

or drinking more alcohol

Target organs

The heart, kidney, brain, and arterial blood vessels are prime targets of hypertensive damage. Uncontrolled hypertension accelerates the damage to these organs and results in eventual organ failure and cardiovascular death and disability.

2.                Classification of arterial hypertension. Risk stratification, associated clinical conditions. Laboratory and instrumental diagnostics. Complications.

Classification of arterial hypertension

1. Primary (essential) hypertension is of unknown etiology. It occurs in 90-95% of cases of hypertension.

2. Secondary hypertension occurs due to some other diseases

Risk stratification

Laboratory and instrumental diagnostics

Chest x-ray may show heart enlargement and abnormal lung

vessels.

Laboratory studies. Autoantibody blood tests may be done to

look for autoimmune diseases like lupus and scleroderma. Liver

function tests may be done to look for cirrhosis or other forms of liver

disease. HIV tests may be done to look for HIV infection.

Echocardiography. This is extremely useful for assessing right

and left ventricular function, estimating pulmonary systolic arterial

pressure, and excluding congenital anomalies and valvular disease.

Findings from echocardiography may demonstrate right-to-left

shunting across a patent foramen ovale in approximately 33% of

patients.

Pulmonary angiography. This test is occasionally required to

help definitively exclude thromboembolic disease. While considered a

high-risk procedure in patients with elevated pulmonary arterial

pressures and/or right ventricular failure, a carefully performed study

is generally safe.

ECG. Results are often abnormal in patients with pulmonary

hypertension, revealing right atrial enlargement, right axis deviation,

right ventricular hypertrophy, and characteristic ST depression and Twave

inversions in the anterior leads. Some patients have few or no

abnormal ECG findings; thus, normal ECG results do not exclude a

diagnosis of pulmonary hypertension.

Cardiac catheterization. This is the criterion standard test to

definitively confirm a pulmonary hypertension. Excluding left-sided

heart disease, including diastolic dysfunction, is especially important

in these patients because of major treatment implications.

Catheterization is also performed to determine vasoreactive status,

which may have implications in the initiation and titration of highdose

calcium channel blocker therapy.

Complications

1. Heart disease (Left ventricular hypertrophy and heart

failure). The left ventricle increases in mass and wall thickness

progressively as a result of the progressive overload and increased left

ventricular wall stress imposed by the increasing arterial pressure and

total peripheral resistance. Ultimately a stable state is reached and

subsequently diastolic dysfunction occurs, associated with a fourth

heart sound, atrial enlargement, and reduced left ventricular

distention.

Ultimately left ventricular systolic function is impaired and

cardiac failure occurs, if arterial pressure and ventricular afterload are

not reduced. Hypertension precedes heart failure in 75 - 90% of heart

failure cases. The best means of preventing morbidity and mortality is

to prevent left ventricular hypertrophy, using early and continuous

antihypertensive therapy.

2. Myocardial ischemia and infarction. Both of these

complications may occur due to increased left ventricular pressure and

left ventricular chamber diameter leading to increased oxygen demand

in left ventricular hypertensive heart disease. Also, hypertension

accelerates the onset of coronary atherosclerosis.

3. Aortic dissection. Currently, the prevalence of this

complication has diminished due to the use of antihypertensive

therapy. One predictive factor seems to be the size of the ascending

aorta at the first examination. It has been shown that patients with an

aortic diameter of less than 5cms had regression of the hematoma

during medical therapy, whereas those with a larger diameter had a

tendency to progression to dissection or rupture. Also, the prognosis

of very old patients is acceptable under medical therapy because of

severe atherosclerosis apparently limiting the expansion of

hemorrhage under blood pressure control.

4. End stage renal disease and nephrosclerosis. More

frequently, essential hypertension is associated with renal arteriolar

thickening, fibrinoid deposition in glomeruli, and proteinuria, which

follow the development of left ventricular hypertrophy.

5. Strokes and Hypertensive encephalopathy. Strokes have

been dramatically reduced with antihypertensive therapy and there has

been at least a 50% reduction in fatal strokes. Hypertensive

encephalopahy is characterized by acute to subacute changes in

neurologic status that occur as a result of elevated arterial pressure and

are reversed by lowering of the blood pressure with effective

antihypertensive therapy within 12 to 72 hours. The CT scan and MRI

can help diagnose focal areas of intracerebral hemorrhage or

infarction.

6. Mental Problems and Dementia. Uncontrolled chronic high

blood pressure is also associated with reduced short-term memory and

mental abilities. Some studies suggest that anti-hypertensive drugs

may help protect against Alzheimer's disease in people with genetic

susceptibility to this disease.

7. Retinal vessel wall changes (retinopathy). Retinal changes

may include retinal hemorrhages, exudates, papilledema, and vascular

accidents. On the basis of retinal changes, Keith, Wagener, and Barker

classified hypertension into groups that have important prognostic

implications: group 1 - constriction of retinal arterioles only; group 2 -

constriction and sclerosis of retinal arterioles, increased reflectiveness

(silver-wiring) of retinal artery; group 3 - hemorrhages, the reflection

shifts toward a bronze color (copper-wiring), may be soft “cottonwool”

exudates in addition to vascular changes; group 4 (malignant

hypertension) - papilledema, hard exudates may collect around fovea,

producing a typical “macular star”.

8. Hypertensive crisis. Hypertensive crises encompass a

spectrum of clinical presentations where uncontrolled blood pressure

leads to progressive or impending target organ dysfunction.

Hypertensive crisis comprises a spectrum of conditions, including

hypertensive urgency and hypertensive emergency.

Hypertensive Urgency. Hypertensive urgency is defined as a

severe elevation of blood pressure, without evidence of progressive

target organ damage. These patients require blood pressure control

over several days to weeks.

Hypertensive Emergency. When damage of organs and systems

occurs (central nervous system, cardiovascular, renal) as a result of

severely elevated high blood pressure, this is considered a

hypertensive emergency. When this occurs, blood pressure must be

reduced immediately to prevent organ damage. This is done in an

intensive care unit of a hospital.

The pathophysiology of hypertensive emergencies is not well

understood. Failure of normal autoregulation and an abrupt rise in

systemic vascular resistance are typically initial steps in the disease

process. This is followed by endovascular injury, with fibrinoid

necrosis within the arterioles. If the process is not stopped, a cycle of

ischemia, platelet deposition, and further autoregulatory dysfunction

ensues. The 4 major organ systems affected by high blood pressure are

the central nervous system, cardiovascular system, renal system and

gravid uterus.

The most common clinical presentations of hypertensive

emergencies are cerebral infarction (24.5%), pulmonary edema

(22.5%), hypertensive encephalopathy (16.3%), and congestive heart

failure (12.0%). Less common presentations include intracranial

hemorrhage, aortic dissection, unstable stenocardia or myocardial

infaction and eclampsia.

Symptoms of hypertensive crisis include: headache, seizure

disorders, chest pain, shortness of breath, edemas

3.                Treatment of arterial hypertension. Prophylaxis.

Treatment of arterial hypertension

DIURETICS

THIAZIDES

 -Hydrochlorothiazide

 -Indapamide

 Loop diuretics

 - Furosemide

 - Ethacrynic acid

 K-sparing diuretics

 - Spironolactone

 - Triamterene

Neurotropic drugs

Centrally acting simpatoplegic drugs

-Methyldopa

-Clonidine

Ganglion-blocking drugs

-Trimethaphan

-Hexamethonium

Adrenergic neuron-blocking drugs

-Guanethidine

-Reserpine

Adrenoceptor antagonists

  1) β –adrenoceptor antagonists (metoprolol, nebivolol, celiprolol, nadolol, atenolol, betaxolol,bisoprolol, acebutolol. esmolol, labetolol)

   2) α-adrenoceptor antagonists (prazosin)

Vasodilators

Arterial

Hydralazine

Minoxidil

Dizoxide

Fenoldopam

Ca channel blockers: verapamil, diltiazem, dihydropyridines (nifedipine, amlodipine, lacidipine, felodipine, isradipine, nisoldipine etc)

Mixed arterial-venous

Sodium nitroprusside

INHIBITORS OF ANGIOTENSIN

n  ANGIOTENSIN-CONVERTING ENZYME (ACE) INHIBITORS

-          Captopril   

-          Enalapril

-          Lisinopril

-          Ramipril  etc

ANGIOTENSIN RECEPTOR –BLOCKING DRUGS (“SARTANS”)

-          LOSARTAN

-          CANDESARTAN

-          IRBESARTAN

-          VALSARTAN

-          EPROSARTAN etc

4.                Hypertensive crises. Classification. Symptoms. Principles of treatment of hypertensive crisis.

Definition

Hypertensive crises encompass a spectrum of clinical presentations where uncontrolled blood pressure leads to progressive or impending target organ dysfunction

Classification

Hypertensive urgency and hypertensive emergency

Hypertensive Urgency: Hypertensive urgency is defined as a

severe elevation of blood pressure, without evidence of progressive

target organ damage. These patients require blood pressure control

over several days to weeks.

Hypertensive Emergency: When damage of organs and systems

occurs (central nervous system, cardiovascular, renal) as a result of

severely elevated high blood pressure, this is considered a

hypertensive emergency. When this occurs, blood pressure must be

reduced immediately to prevent organ damage. This is done in an

intensive care unit of a hospital.

Symptoms

headache, seizure disorders, chest pain, shortness of breath, edemas

Principles of treatment of hypertensive crisis

Hypertensive emergency

Nitroglycerine

Labetalol

Enalaprilate

Clonidine

Hydralazine

Esmolol

All of the above are given in IV infusions only

You have 2hr to reduce blood pressure the first hour you reduce it by 25% and the next hour, you reduce the blood pressure to the target level

Hypertensive urgency

1^st hour reduce by 25% and the next few days reduce the BP the target level gradually

Sublingually

Captopril

Nifedipine ( contra-indication – Patient with IHD)

Nitroglycerine

Monoxidine

Beta-blockers

5.                Symptomatic (secondary) arterial hypertension. Classification.  Features their clinical manifestations.

Secondary hypertension is the result of another condition or

disorder, it has a known cause. It occurs in 5-10% of the cases of

hypertension

Classification

1) renal parenchymal diseases (chronic glomerulonephritis or

pyelonephritis, polycystic renal disease, collagen disease of the

kidney, obstructive uropathy, amyloidosis),

2) renal arterial diseases - renovascular hypertension (nonatherosclerotic

renal arterial disease, atherosclerotic renal arterial

disease, embolic renal arterial disease, extravascular compression of

the renal artery by tumor),

3) endocrine diseases (pheochromocytoma, Cushing's

syndrome, primary aldosteronism, hyperthyroidism, myxedema,

hyperparathyroidism),

4) coarctation of the aorta,

5) sleep apnea,

6) brain tumor, stroke or other disorders associated with

increased intracranial pressure

7) excessive dietary sodium intake,

8) use of some medicines (oral contraceptives,

sympathomimetics, corticosteroids, cocaine, or licorice)

Features their clinical manifestations

Hypertension associated with chronic renal parenchymal disease

results from combination of a renin-dependent mechanism and a

volume-dependent mechanism. Any number of pathologic processes

(diabetic nephropathy, glomerulonephritis, pyelonephritis) can

damage nephrons in the kidney.

 When this occurs, the kidney cannot excrete normal amounts of sodium which leads to sodium and water

retention, increased blood volume, and increased cardiac output by the

Frank-Starling mechanism. Renal disease may also result in increased

release of renin leading to a renin-dependent form of hypertension.

The elevation in arterial pressure secondary to renal disease can be

viewed as an attempt by the kidney to increase renal perfusion and

restore glomerular filtration. Proteinuria, cylindruria, or

microhematuria with or without nitrogen retention early in the course

of hypertension is strong evidence of underlying primary renal

disease.

Renovascular disease causes stenosis the renal vessels. The

reduced lumen diameter increases the pressure drop along the length

of the diseased artery, which reduces the pressure at the afferent

arteriole in the kidney. Reduced arteriolar pressure and reduced renal

perfusion stimulate renin release by the kidney.

 This increases circulating angiotensin II and aldosterone. These hormones increase

blood volume by enhancing renal reabsorption of sodium and water.

Increased angiotensin II causes systemic vasoconstriction and

enhances sympathetic activity. Chronic elevation of angiotensin II

promotes cardiac and vascular hypertrophy. The net effect of these

renal mechanisms is an increase in blood volume that augments

cardiac output by the Frank-Starling mechanism. 

Therefore, hypertension caused by renal artery stenosis results from both an

increase in systemic vascular resistance and an increase in cardiac

output. 

Renovascular hypertension is suspected in patients with

resistant arterial hypertension. We may find abdominal murmurs

during auscultation, stenosis during renal artery ultrasonography and

increased plasma renin activity.

Pheochromocytoma. Catecholamine secreting tumors in the

adrenal medulla can lead to very high levels of circulating

catecholamines (both epinephrine and norepinephrine). This leads to

alpha-adrenoceptor mediated systemic vasoconstriction and betaadrenoceptor

mediated cardiac stimulation, both of which contribute

to significant elevations in arterial pressure. 

Despite the elevation in arterial pressure, tachycardia occurs because of the direct effects of

the catecholamines on the heart and vasculature. Excessive betaadrenoceptor

stimulation in the heart often leads to arrhythmias.

Pheochromocytoma besides elevating blood pressure, usually produce

symptoms (various combinations of headache, palpitations,

tachycardia, excessive perspiration, tremor, and pallor) that should

alert the physician to this possibility. 

Catecholamines (epinephrine, norepinephrine) are eventually metabolized in the body to a common

product, 3-methoxy-4-hydroxymandelic acid, often called

vanillylmandelic acid. Diagnosis depends on demonstrating increased

urinary or plasma concentrations of catecholamine or increased

urinary concentrations of metanephrines and vanillylmandelic acid.

Cushing syndrome is caused by excessive amounts of a steroid

hormone cortisol, produced in the cortex of the adrenal glands. This

can be caused by a tumor in the adrenal glands, a tumor in the

pituitary gland in the brain, or a cortisol-secreting tumor anywhere

else in the body (ectopic Cushing syndrome). Cushing's syndrome

suspected in patients with clinical symptoms and signs: central

obesity, characteristic skin lesions, fatigue, muscle weakness and

atrophy. 
They may have increased cortisol concentration after

dexamethasone, increased 24-h urinary cortisol excretion test and

presence of adrenal hypertrophy or tumor in brain magnetic resonance

imaging.

Primary Hyperaldosteronism. Increased secretion of aldosterone

generally results from adrenal adenoma or adrenal hyperplasia.

Increased circulating aldosterone causes renal retention of sodium and

water, so blood volume and arterial pressure increase. Plasma renin

levels are generally decreased as the body attempts to suppress the

renin-angiotensin system; there is also hypokalemia associated with

the high levels of aldosterone. Hypokalemia not due to diuretics

should suggest primary aldosteronism.

Hyper- or hypothyroidism. Excessive thyroid hormone induces

systemic vasoconstriction, an increase in blood volume, and increased

cardiac activity, all of which can lead to hypertension.
It is less clear why some patients with hypothyroidism develop hypertension, but it

may be related to decreased tissue metabolism reducing the release of

vasodilator metabolites, thereby producing vasoconstriction and

increased systemic vascular resistance. Hyperthyrodism or

hypothyrodism may be diagnosed by changed thyroid hormones level

in plasma.

Coarctation of the aorta (typically just distal to the left

subclavian artery), is a congenital defect that obstructs aortic outflow

leading to elevated pressures proximal to the coarctation (elevated

arterial pressures in the head and arms). Distal pressures, however, are

not necessarily reduced as would be expected from the hemodynamics

associated with a stenosis.

 The reason for this is that reduced systemic

blood flow, and in particular reduced renal blood flow, leads to an

increase in the release of renin and an activation of the reninangiotensin-

aldosterone system. This in turn elevates blood volume

and arterial pressure. Although the aortic arch and carotid sinus baroreceptors are exposed to higher than normal pressures, the baroreceptor reflex is blunted due to structural changes in the walls of

vessels where the baroreceptors are located.

 Also, baroreceptors become desensitized to chronic elevation in pressure and become

"reset" to the higher pressure. Absent or markedly reduced and

delayed femoral arterial pulses in a hypertensive patient aged < 30

year are presumptive evidence of coarctation of the aorta.

Cerebral tumor may be suspected in patients with headache and

neurological abnormalities. It may be diagnosed by brain magnetic

resonance imaging.

Drug-induced hypertension may be diagnosed by obtaining

clinical history (special attention must be paid to intake of drugs or

substances that can raise blood pressure: steroids, oral contraceptives,

non-steroidal anti-inflammatory drugs, liquorice, cocaine,

amphetamines, erythropoietin, cyclosporins).

Sleep apnea is a disorder in which people repeatedly stop

breathing for short periods of time (10-30 seconds) during their sleep.

This condition is often associated with obesity, although it can have

other causes such as airway obstruction or disorders of the central

nervous system. These individuals have a higher incidence of

hypertension. The mechanism of hypertension may be related to

sympathetic activation and hormonal changes associated with repeated

periods of apnea-induced hypoxia and hypercapnea, and from stress

associated with the loss of sleep.

6.                Diagnosis and differential diagnosis of renal artery hypertension (parenchymal, renovascular). Principles of treatment

Diagnosis and differential diagnosis of renal artery hypertension (parenchymal)

Diagnosis

Hypertension associated with renal parenchymal disease

results from combination of a renin-dependent mechanism and a

volume-dependent mechanism. Any number of pathologic processes

(diabetic nephropathy, glomerulonephritis, pyelonephritis) can

damage nephrons in the kidney. When this occurs, the kidney cannot

excrete normal amounts of sodium which leads to sodium and water

retention, increased blood volume, and increased cardiac output by the

Frank-Starling mechanism. Renal disease may also result in increased

release of renin leading to a renin-dependent form of hypertension.

The elevation in arterial pressure secondary to renal disease can be

viewed as an attempt by the kidney to increase renal perfusion and

restore glomerular filtration. Proteinuria, cylindruria, or

microhematuria with or without nitrogen retention early in the course

of hypertension is strong evidence of underlying primary renal

disease

differential diagnosis

Renal carcinoma

Enlarging renal cyst

Multiple renal cysts

Renin-secreting tumors

Treatment

Diuretics:

Thiazide class

Loop diuretics

Potassium-sparing agents

Adrenergic inhibitors

Peripheral agents, eg, guanethidine

Central -agonists, eg, clonidine, methyldopa, and guanfacine

-Blocking agents, eg, doxazosin

-Blocking agents

Combined - blocking agents, eg, labetalol

Vasodilators

Hydralazine

Minoxidil

Classes of calcium-channel blocking agents

Verapamil

Diltiazem

Dihydropyridine

Angiotensin-converting enzyme inhibitors

Angiotensin receptor blockers.

 dfferential diagnosis of renal artery hypertension (renovascular)

Diagnosis

When appropriate, imaging of the renal vasculature

with either CT angiography or MR angiography should

be performed to confirm the diagnosis). Both

give good views of the main renal arteries, the vessels

predominantly involved and the most amenable to intervention.

Biochemical testing may reveal impaired renal

function and an elevated plasma renin activity, sometimes

with hypokalaemia due to hyperaldosteronism.

Ultrasound may also reveal a discrepancy in size

between the two kidneys. While these investigations provide supportive information, they are insufficiently

sensitive or specific to be of value in diagnosis of renovascular

disease in hypertensive patients

Differential diagnosis

·         Acute Kidney Injury

·         Atherosclerosis

·         Azotemia

·         Chronic Glomerulonephritis

·         Hypersensitivity Nephropathy

·         Hypertension

·         Malignant Hypertension

·         Nephrosclerosis

·         Renovascular Hypertension

·         Uremia

Principles of treatment

The first-line management in patients with renal artery

stenosis is medical therapy with antihypertensive

drugs, supplemented, where appropriate, by statins

and low-dose aspirin in those with atherosclerotic

disease. Interventions to correct the vessel narrowing

should be considered in young patients (age below 40)

suspected of having renal artery stenosis; those in whom

blood pressure cannot easily be controlled with antihypertensive

agents; those who have a history of ‘flash’

pulmonary oedema or accelerated phase (malignant)

hypertension; and those in whom renal function is deteriorating.

The most commonly used technique is angioplasty.

The best results are obtained in non-atheromatous

fibromuscular dysplasia, where correction of the stenosis

has a high chance of success in improving blood

pressure and protecting renal function. Angioplasty and

stenting can sometimes be successful in atherosclerotic

disease but randomised trials have produced no convincing

evidence for overall benefit in terms of renal

function or blood pressure control. The risks of angioplasty and stenting

include renal artery occlusion, renal infarction, and atheroemboli

from manipulations in a severely diseased aorta. Small vessel

disease distal to the stenosis may preclude substantial functional recovery

7.                Diagnosis and differential diagnosis of endocrine arterial hypertension (thyrotoxic, with Cushing's syndrome, pheochromocytoma). Principles of treatment.

Cushing's syndrome

Diagnosis

Cushing syndrome is caused by excessive amounts of a steroid

hormone cortisol, produced in the cortex of the adrenal glands.
 This can be caused by a tumor in the adrenal glands, a tumor in the

pituitary gland in the brain, or a cortisol-secreting tumor anywhere

else in the body (ectopic Cushing syndrome). Cushing's syndrome

suspected in patients with clinical symptoms and signs: central

obesity, characteristic skin lesions, fatigue, muscle weakness and

atrophy. They may have increased cortisol concentration after

dexamethasone, increased 24-h urinary cortisol excretion test and

presence of adrenal hypertrophy or tumor in brain magnetic resonance

imaging

8.                Diagnosis and differential diagnosis of hemodynamic and cerebral arterial hypertension. Principles of treatment.

9.                Somatoform vegetative (autonomic) dysfunction. Definition. Etiology and pathogenesis. Classification.

10.           The diagnostic criteria for somatoform vegetative (autonomic) dysfunction. The principles of treatment, pharmacological and non-pharmacological therapy.

11.           Atherosclerosis. Risk factors. Pathogenesis.

Atherosclerosis is a disease of large and medium-sized muscular

arteries and is characterized by endothelial dysfunction, vascular

inflammation, and the accumulation of lipids, cholesterol, calcium,

and cellular debris within the intima of the vessel wall. This

accumulation results in plaque formation, vascular remodeling, acute

and chronic luminal obstruction, abnormalities of blood flow and

diminished oxygen supply to target organs

Risk factors

The major risk factors that can't be changed

1. Advanced age. Over 83 % of people who die of coronary

heart disease are 65 or older.

2. Male sex (gender). Men have a greater risk of heart attack

than women do, and they have attacks earlier in life. Even after

menopause, women's death rate from heart diseases increases, but

insignificantly compared to men's.

3. Heredity. Children whose parents suffer from heart diseases

or atherosclerosis are more likely to develop it themselves. Most

people with a strong family history of heart disease have one or more

other risk factors.

The major risk factors that can be modified (treat or control by

changing lifestyle or taking medicine)

1. High blood cholesterol (elevated serum cholesterol or

triglyceride levels). Total serum cholesterol is carried in the blood by

low-density lipoprotein (LDL) (“bad cholesterol”), very low-density

lipoprotein (VLDL) and high-density lipoprotein (HDL) (“good

cholesterol”). The higher is the LDL cholesterol level, the higher is

the risk of atherosclerosis. Conversely, high levels of HDL cholesterol

seem to be protective. One theory is that HDL may allow for elution

of cholesterol out of the vessels. High triglycerides are associated with

low HDL cholesterol and are a probable risk factor for vascular

disease.

2. Tobacco smoking. Smokers' risk of developing

atherosclerosis and coronary heart disease is 2–4 times higher than

that of nonsmokers. Smoking increases carbon monoxide levels in the

blood, which may, in turn, damage the endothelium of vessels.

Smoking also increases platelet adhesion and thus the likelihood of

thrombotic artery occlusion. Cigarette smoking is a powerful

independent risk factor for sudden cardiac death in patients with

coronary heart disease; smokers have about twice the risk of

nonsmokers. Cigarette smoking also acts with other risk factors to

greatly increase the risk for coronary heart disease. Exposure to other

people's smoke increases the risk of heart disease even for

nonsmokers.

3. High blood pressure. High blood pressure increases the

heart's workload, causing the heart to thicken and become stiffer. It

also increases the risk of stroke, heart attack, kidney failure and

congestive heart failure. When high blood pressure associates with

obesity, smoking, high blood cholesterol levels or diabetes, the risk of

heart attack or stroke increases in several times.

4. Obesity and overweight (in particular central obesity, also

referred to as abdominal or male-type obesity). People who have

excess body fat – especially around the waist – are more likely to

develop heart disease and stroke even if they have no other risk

factors. Excess weight increases the heart's work. It also raises blood

pressure and blood cholesterol and triglyceride levels, and lowers

HDL ("good") cholesterol levels. It can also make diabetes more

likely to develop. Many obese and overweight people may have

difficulty losing weight. But by losing even as few as 10 pounds,

person can lower his heart disease risk.

5. Diabetes mellitus or impaired glucose tolerance. Diabetes

seriously increases the risk of developing cardiovascular disease. Even

when glucose levels are under control, diabetes increases the risk of

heart disease and stroke, but the risks are even greater if blood sugar is

not well controlled. About three-quarters of people with diabetes die

of some form of heart or blood vessel disease.

6. Physical inactivity. An inactive lifestyle is a risk factor for

coronary heart disease. Regular, moderate-to-vigorous physical

activity helps prevent heart and blood vessel disease. The more

vigorous the activity is the greater benefits are. However, even

moderate-intensity activities help if done regularly and long term.

Exercise can help control blood cholesterol, diabetes and obesity, as well as help lower blood pressure in some people.

7. Stress or symptoms of clinical depression. Individual

response to stress may be a contributing factor. Some scientists have

noted a relationship between coronary heart disease risk and stress in a

person's life, their health behaviors and socioeconomic status. These

factors may affect established risk factors. For example, people under

stress may overeat, start smoking or smoke more than they otherwise

would.

8. Drinking too much alcohol can raise blood pressure, cause

heart failure and lead to stroke. It can contribute to high triglycerides,

cancer and other diseases, and produce irregular heartbeats. It

contributes to obesity, alcoholism, suicide and accidents. The risk of

heart disease in people who drink moderate amounts of alcohol (an

average of one drink for women or two drinks for men per day) is

lower than in nondrinkers. One drink is defined as 1-1/2 fluid ounces

(fl oz) of 80-proof alcohol (such as bourbon, Scotch, vodka, gin), 1 fl

oz of 100-proof alcohol, 4 fl oz of wine or 12 fl oz of beer. It's not

recommended that nondrinkers start using alcohol or that drinkers

increase the amount they drink.

9. Some other risk factors, such as: elevated serum levels of

homocysteine, elevated serum fibrinogen concentrations, elevated

serum levels of C-reactive protein, chronic systemic inflammation

may also predispose to atherosclerosis.

Pathogenesis

The most widely accepted theory of atherosclerosis holds that the process represents an attempt at healing in response to endothelial injury due to hypercholesterolemia or

hypertension. The first step in the atherosclerotic process is the

development of fatty streaks, which contain atherogenic lipoproteins

and macrophage foam cells. 

These streaks form between the endothelium and the internal elastic lamina. This may be the earliest

stage of the disease found in late teens and young adults. The fatty

streak may progress to form a fibrous plaque (atheroma), the result of

progressive lipid accumulation and the migration and proliferation of

smooth muscle cells. 

The edge of the fibrous cap (the "shoulder" region) plays a critical role in the development of acute coronary

syndromes. The shoulder region is the site where most plaques lose

their integrity or rupture. The atherosclerotic plaque undergoes

change and extension with erosion, rupture, and ulceration, leading to

activation of platelets and thrombus development. This exposure

results in platelet adherence, aggregation, and progressive luminal

narrowing that are associated with acute coronary syndromes. The

forth stage of atherogenesis is calcification, which produce

deformation and narrowing of the vessels.

Atherosclerotic plaques characteristically occur in regions of

branching and marked curvature at areas of geometric irregularity and

where blood undergoes sudden changes in velocity and direction of

flow. Decreased shear stress and turbulence may promote

atherogenesis at these important sites within the coronary arteries, the

major branches of the thoracic and abdominal aorta, and the large

conduit vessels of the lower extremities

12.           Atherosclerosis: clinical manifestations depending on the location. Instrumental and laboratory methods of investigations for establish diagnosis.

Atherosclerosis: clinical manifestations depending on the location

The symptoms of atherosclerosis are highly variable. Patients

with mild atherosclerosis may present with clinically important

symptoms and signs of disease and myocardial infarction, or sudden

cardiac death may be the first symptom of coronary heart disease.

However, many patients with anatomically advanced disease may

have no symptoms and experience no functional impairment. Initially

thought to be a chronic, slowly progressive, degenerative disease, it is

now apparent that atherosclerosis is a disease with periodic activity

and quiescence. Although a systemic disease, atherosclerosis

manifests in a focal manner and affects different organ and systems in

different patients for reasons that remain unclear.

Atherosclerosis can follow two main pathways. Firstly, the

atheromatous plaques cause stenosis (narrowing) of the artery and,

therefore, an insufficient blood supply to the organ it feeds. 

This complication is chronic, slowly progressing. Stable stenocardia,

intermittent claudication, and mesenteric angina are examples of the

clinical consequences of this mismatch. Secondly, the soft plaque may

suddenly rupture (see vulnerable plaque), causing the formation of a

blood clot (thrombus) that will rapidly stop blood flow, leading to

death of the tissues fed by the artery. This catastrophic event is called

an infarction. Unstable stenocardia, myocardial infarction, transient

ischemic attack, and stroke are examples of the clinical sequelae of

partial or complete acute occlusion of an artery.

Symptoms of atherosclerosis differ depending upon the location

of the atherosclerosis.

Coronary arteries. Stenocardia is characterized by retrosternal

chest discomfort that typically radiates to the left arm and may be

associated with dyspnea. Stenocardia is exacerbated by exertion and

relieved by rest or nitrate therapy. 
Unstable stenocardia describes a pattern of increasing frequency or intensity of episodes of stenocardia

and includes pain at rest. A prolonged episode of stenocardia that may

be associated with diaphoresis is suggestive of myocardial infarction.

Carotid and brain arteries. Stroke, reversible ischemic

neurological deficit, and transient ischemic attack are a range of

manifestations of impairment of vascular supply to the central nervous

system and are characterized by the sudden onset of a focal

neurological deficit of variable duration, respectively.

Femoral arteries (or the blood vessels in the outer parts of the

body). Peripheral vascular disease typically manifests as intermittent

claudication, impotence, and nonhealing ulceration and infection of

the extremities. Intermittent claudication is described as calf, thigh, or

buttock pain that is exacerbated by exercise and relieved by rest.

Intermittent claudication may be accompanied by pallor of the

extremity and paresthesias. Gangrene and amputation of the extremity

may result due to thrombosis of the artery.

Renal arteries. High blood pressure that is difficult to treat and

kidney failure.

Visceral arteries. Visceral ischemia may be occult or

symptomatic prior to symptoms and signs of target organ failure.

Mesenteric angina is characterized by epigastric or periumbilical

postprandial pain and may be associated with hematemesis,

hematochezia, melena, diarrhea, nutritional deficiencies, and weight

loss. Thrombosis of mesenteric arteries leads to necrosis of some part

of the intestine. Resection of necrotic part of the intestine may save

patient's life. Prognosis is unfavorable in case of total necrosis of

intestine.

Instrumental and laboratory methods of investigations for establish diagnosis

Laboratory studies. Routine laboratory measurements

recommended as a part of the initial evaluation of patients with

chronic stable angina should include a serum hemoglobin, fasting

glucose, and fasting lipids levels (total cholesterol, HDL cholesterol,

triglycerides, and calculated LDL cholesterol). Other markers, such as

plasma homocysteine, lipoprotein (A) and high-sensitivity C-reactive

protein, may be useful in assessing cardiac risk.

Normal serum levels:

- total cholesterol 3.9-5.2 mmol/l

- HDL cholesterol 1.0-1.9 mmol/l

- triglycerides 0.55-1.65 mmol/l.

ECG. ECG may be normal in several patients at rest in between

attacks of stenocardia. However, during the episodes of pain there

may be depression of the ST segment and a T wave inversion in

several leads, indicating ischemia. ST segment elevation, decreased Rwave

height, intraventricular or bundle branch conduction

disturbances and arrhythmia (usually ventricular extrasystoles) also

may indicate ischemia.

Echocardiography. Echocardiography is recommended for

patients with stable angina and physical findings suggesting

concomitant valvular heart disease. It is also recommended for the

assessment of global and regional left ventricular systolic function in

patients who have Q waves in electrocardiogram, congestive heart

failure, complex ventricular arrhythmias, or a history of a past

myocardial infarction. Echocardiography also readily assesses the

pericardial space. This method is non-invasive and is readily portable.

Stress testing. Stress testing is a means to further assess the

presence of flow-limiting, functionally significant coronary artery

disease. All stress testing techniques include electrocardiogram and

blood pressure monitoring.

Cardiovascular stress testing is taken in two forms - exercise and

pharmacologic administration. The preferred method of

cardiovascular stress testing is exercise, utilizing a treadmill or

bicycle. Through aerobic exercise, one achieves a greater rate pressure

product (the product of peak systolic blood pressure and peak pulse

rate) and therefore greater cardiovascular stress. 

This permits an assessment of an individual's functional capacity, and observation of

the effects of exercise on the patient's symptoms, heart rate and blood

pressure.

The appearance of horizontal or downsloping ST segment

depression of 1 mm or more during exercise has a sensitivity of

approximately 70% and a specificity of 90% for the detection of

coronary disease.

The most common pharmacologic agents used for non-exercise

stress testing are dobutamine, dipyridamole, and adenosine.

Dobutamine is both a beta-receptor 1 and beta-receptor 2 agonist,

increasing myocardial contractility, heart rate, and inducing peripheral

vasodilation, as a result raising myocardial oxygen demand. It is

usually combined with echocardiography.

Dobutamine echocardiography is useful in assessing for the presence of

functionally significant obstructive coronary artery disease and also in

assessing a post-myocardial infarction patient. With the help of

echocardiography, emphasis is put on the global and regional

endocardial response to cardiovascular stress.

 Under normal circumstances, the end systolic left ventricular volume at peak stress

diminishes and endocardial thickening is symmetrically enhanced. In

the case of pathology, a regional decrement of endocardial thickening

is observed, supporting inducible myocardial ischemia. In the

presence of advanced multivascular coronary artery disease, the left

ventricle actually dilates and a marked reduction in global endocardial

thickening is observed.

Radionuclide imaging. Radionuclide imaging is performed with

thallium-201 or technetium (Tc) 99m. With the help of nuclear

perfusion imaging, functionally significant coronary artery disease is

suspected when an area of relative hypoperfusion is detected on peakstress

images when compared with the resting images. Resting nuclear

cardiac imaging may also be abnormal.

 These abnormalities reflect a chronic low blood flow state to the abnormal region of myocardium.

This may represent either a chronic low blood flow state to

dysfunctional yet viable myocardium versus a completed infarction

and non-viable myocardial tissue, best termed myocardial "scar."

Coronary arteriography. Cardiac catheterization is currently

the "gold standard" for determining the presence of obstructive

coronary artery disease. The images are obtained in real time, with a

percentage lumen diameter readily calculated. A routine cardiac

catheterization may demonstrate the somewhat smaller coronary

arteries with a distal, tapered appearance.

13.           Primary and secondary prevention of atherosclerosis. Treatment of atherosclerosis

Primary prevention

Two complementary strategies can be used to prevent

atherosclerosis in apparently healthy but at-risk individuals:

population and targeted strategies.

The population strategy aims to modify the risk

factors of the whole population through diet and lifestyle

advice, on the basis that even a small reduction in

smoking or average cholesterol, or modification of exercise

and diet will produce worthwhile. Some risk factors for atheroma, such as obesity

and smoking, are also associated with a higher risk of

other diseases and should be actively discouraged

through public health measures. Legislation restricting

smoking in public places is associated with reductions

in rates of MI.

The targeted strategy aims to identify and treat

high-risk individuals, who usually have a combination

of risk factors and can be identified by using composite

scoring systems . It is important to consider

the absolute risk of atheromatous cardiovascular disease

that an individual is facing before contemplating specific

antihypertensive or lipid-lowering therapy because this

will help to determine whether the possible benefits of

intervention are likely to outweigh the expense, inconvenience

and possible side-effects of treatment.

 For example, a 65-year-old man with an average BP of

150/90 mmHg, who smokes and has diabetes mellitus,

a total : HDL cholesterol ratio of 8 and left ventricular

hypertrophy on ECG, will have a 10-year risk of coronary

artery disease of 68% and a 10-year risk of any

cardiovascular event of 90%. Lowering his cholesterol

will reduce these risks by 30% and lowering his BP will

produce a further 20% reduction; both would obviously

be worthwhile.

 Conversely, a 55-year-old woman who

has an identical BP, is a non-smoker, does not have

diabetes mellitus and has a normal ECG and a total : HDL

cholesterol ratio of 6 has a much better outlook, with a

predicted coronary artery disease risk of 14% and cardiovascular

risk of 19% over the next 10 years. Although

lowering her cholesterol and BP would also reduce risk

by 30% and 20% respectively, the value of either or both

treatments is questionable

Secondary prevention

Patients who already have evidence of atheromatous

vascular disease are at high risk of future cardiovascular

events and should be offered treatments and measures

to improve their outlook.

 The energetic correction of modifiable risk factors, particularly smoking, hypertension

and hypercholesterolaemia, is particularly important

because the absolute risk of further vascular events

is high. All patients with coronary artery disease should

be given statin therapy, irrespective of their serum cholesterol

concentration. BP should be treated

to a target of 140/85 mmHg or lower. 

Aspirin and ACE inhibitors are of benefit in patients with evidence

of vascular disease (Boxes 18.47 and 18.48). Betablockers

benefit patients with a history of MI  or heart failure.

Many clinical events offer an unrivalled opportunity

to introduce effective secondary preventive measures;

patients who have just survived an MI or undergone

bypass surgery are usually keen to help themselves and

may be particularly receptive to lifestyle advice, such as

dietary modification and smoking cessation

Treatment of atherosclerosis

Medications

Various drugs can slow — or even reverse — the effects of atherosclerosis. Here are some common choices:

·         Cholesterol medications. Aggressively lowering your low-density lipoprotein (LDL) cholesterol, the "bad" cholesterol, can slow, stop or even reverse the buildup of fatty deposits in your arteries. Boosting your high-density lipoprotein (HDL) cholesterol, the "good" cholesterol, may help, too.

Your doctor can choose from a range of cholesterol medications, including drugs known as statins and fibrates. In addition to lowering cholesterol, statins have additional effects that help stabilize the lining of your heart arteries and prevent atherosclerosis.

·         Anti-platelet medications. Your doctor may prescribe anti-platelet medications, such as aspirin, to reduce the likelihood that platelets will clump in narrowed arteries, form a blood clot and cause further blockage.

·         Beta blocker medications. These medications are commonly used for coronary artery disease. They lower your heart rate and blood pressure, reducing the demand on your heart and often relieve symptoms of chest pain. Beta blockers reduce the risk of heart attacks and some heart rhythm problems.

·         Angiotensin-converting enzyme (ACE) inhibitors. These medications may help slow the progression of atherosclerosis by lowering blood pressure and producing other beneficial effects on the heart arteries. ACE inhibitors can also reduce the risk of recurrent heart attacks.

·         Calcium channel blockers. These medications lower blood pressure and are sometimes used to treat angina.

·         Water pills (diuretics). High blood pressure is a major risk factor for atherosclerosis. Diuretics lower blood pressure.

·         Other medications. Your doctor may suggest certain medications to control specific risk factors for atherosclerosis, such as diabetes. Sometimes specific medications to treat symptoms of atherosclerosis, such as leg pain during exercise, are prescribed.

Surgical procedures

Sometimes more aggressive treatment is needed to treat atherosclerosis. If you have severe symptoms or a blockage that threatens muscle or skin tissue survival, you may be a candidate for one of the following surgical procedures:

·         Angioplasty and stent placement. In this procedure, your doctor inserts a long, thin tube (catheter) into the blocked or narrowed part of your artery. A second catheter with a deflated balloon on its tip is then passed through the catheter to the narrowed area.

The balloon is then inflated, compressing the deposits against your artery walls. A mesh tube (stent) is usually left in the artery to help keep the artery open.

·         Endarterectomy. In some cases, fatty deposits must be surgically removed from the walls of a narrowed artery. When the procedure is done on arteries in the neck (the carotid arteries), it's called a carotid endarterectomy.

·         Fibrinolytic therapy. If you have an artery that's blocked by a blood clot, your doctor may use a clot-dissolving drug to break it apart.

·         Bypass surgery. Your doctor may create a graft bypass using a vessel from another part of your body or a tube made of synthetic fabric. This allows blood to flow around the blocked or narrowed artery

14.           Coronary artery disease. Etiology, pathogenesis.

Coronary artery disease (CAD), also known as ischemic heart disease (IHD), is a group of diseases that includes: stable angina, unstable angina, myocardial infarction, and sudden cardiac death

Etiology

Stable angina Ischaemia due to fixed atheromatous

stenosis of one or more coronary arteries

Unstable angina Ischaemia caused by dynamic obstruction

of a coronary artery due to plaque rupture

or erosion with superimposed thrombosis

Myocardialinfarction

Myocardial necrosis caused by acute

occlusion of a coronary artery due to

plaque rupture or erosion with

superimposed thrombosis

Heart failure Myocardial dysfunction due to infarction

or ischaemia

Arrhythmia Altered conduction due to ischaemia or

infarction

Sudden death Ventricular arrhythmia, asystole or

massive myocardial infarction

Pathogenesis

Limitation of blood flow to the heart causes ischemia (cell starvation secondary to a lack of oxygen) of the myocardial cells. Myocardial cells may die from lack of oxygen and this is called a myocardial infarction (commonly called a heart attack). It leads to heart muscledamage, heart muscle death and later myocardial scarring without heart muscle regrowth. Chronic high-grade stenosis of the coronary arteries can induce transient ischemia which leads to the induction of a ventricular arrhythmia, which may terminate into ventricular fibrillation leading to death.

Typically, coronary artery disease occurs when part of the smooth, elastic lining inside a coronary artery (the arteries that supply blood to the heart muscle) develops atherosclerosis. With atherosclerosis, the artery's lining becomes hardened, stiffened, and swollen with calcium deposits, fatty deposits, and abnormal inflammatory cells - to form a plaque. Deposits of calcium phosphates (hydroxyapatites) in the muscular layer of the blood vessels appear to play not only a significant role in stiffening arteries but also for the induction of an early phase of coronary arteriosclerosis. This can be seen in a so-called metastatic mechanism of calciphylaxis as it occurs in chronic kidney disease and haemodialysis (Rainer Liedtke 2008). Although these patients suffer from a kidney dysfunction, almost fifty percent of them die due to coronary artery disease. Plaques can be thought of as large "pimples" that protrude into the channel of an artery, causing a partial obstruction to blood flow. Patients with coronary artery disease might have just one or two plaques, or might have dozens distributed throughout their coronary arteries. A more severe form is chronic total occlusion (CTO), when a coronary artery is completely obstructed for more than 3 months.

Cardiac syndrome X is a term that describes chest pain (angina pectoris) and chest discomfort in people who do not show signs of blockages in the larger coronary arteries of their hearts when an angiogram (coronary angiogram) is being performed.The exact cause of cardiac syndrome X is unknown. One explanation is microvascular dysfunction. For reasons that are not well known, women are more likely than men to have it; however, hormones and other risk factors unique to women may play a role

15.           Risk factors of coronary artery disease and their role. Classification of CAD. Sudden death, definition

Risk factors of coronary artery disease and their role

Coronary artery disease has a number of well determined risk factors. The most common risk factors include smoking, family history, hypertension, obesity, diabetes, lack of exercise, stress, and high blood lipids.^] Smoking is associated with about 36% of cases and obesity 20%.Lack of exercise has been linked to 7–12% of cases. Exposure to the herbicide Agent orange may increase risk. Both rheumatoid arthritis and systemic lupus erythematosus are independent risk factors as well.

Job stress appears to play a minor role accounting for about 3% of cases.

In one study, women who were free of stress from work life saw an increase in the diameter of their blood vessels, leading to decreased progression of atherosclerosis. In contrast, women who had high levels of work-related stress experienced a decrease in the diameter of their blood vessels and significantly increased disease progression.Having a type A behavior pattern, a group of personality characteristics including time urgency, competitiveness, hostility, and impatience is linked to an increased risk of coronary disease.

Blood fats

·         High blood cholesterol (specifically, serum LDL concentrations). HDL (high density lipoprotein) has a protective effect over development of coronary artery disease.

·         High blood triglycerides may play a role.

·         High levels of lipoprotein(a), a compound formed when LDL cholesterol combines with a protein known as apolipoprotein(a).

Dietary cholesterol does not appear to have a significant effect on blood cholesterol and thus recommendations about its consumption may not be needed. Saturated fat is still a concern.

Other

·         Endometriosis in women under the age of 40

·         It is unclear if type A personality affects the risk of coronary artery disease. Depression and hostility do appear to be risks however.

·         The number of categories of adverse childhood experiences (psychological, physical, or sexual abuse; violence against mother; or living with household members who were substance abusers, mentally ill, suicidal, or incarcerated) showed a graded relationship to the presence of adult diseases including coronary artery (ischemic heart) disease.

·         Hemostatic factors: High levels of fibrinogen and coagulation factor VII are associated with an increased risk of CAD. Factor VII levels are higher in individuals with a high intake of dietary fat. Decreased fibrinolytic activity has been reported in patients with coronary atherosclerosis. Low hemoglobin^[

·         Men over 45; Women over 55

Classification of CAD

1. Sudden coronary death (primary cardiac arrest)

2. Stenocardia

2.1. Stable angina (chronic stenocardia)

2.2. Silent (asymptomatic) myocardial ischemia

2.3. Unstable angina

2.3.1. New onset stenocardia

2.3.2. Rest stenocardia

2.4. Variant (Prinzmetal's) vasospastic angina

3. Myocardial infarction

3.1. Transmural myocardial infarction (with Q wave)

3.2. Sub-endocardial myocardial infarction (without Q wave)

4. Post-infarction cardiosclerosis

5. Arrhythmias

6. Heart failure

Sudden death, definition

Sudden coronary death is defined as death within one hour of the

onset of symptoms of acute myocardial ischemia. Sudden cardiac

death in patients with ischemic heart disease is usually caused by an

abnormal heart rhythm called ventricular fibrillation, which prevents

the heart from contracting and thus stops all blood flow to the brain

and other vital organs. The patient will die unless he or she receives

cardiopulmonary resuscitation and electric shock with an external

defibrillator to restart the heart and resume blood flow, quickly

16.           Stable angina. Classification. Diagnostic criteria. Mechanism of pain syndrome in angina.

Stable angina

Angina that occurs regularly with activity, upon awakening, or at

other predictable times is termed stable angina and is associated with

high grade narrowing of the coronary arteries.

Classification

Diagnostic criteria

Stenocardia is said to be stable when the pattern of its frequency, intensity, ease of

provocation, or duration does not change over a several-week period.

Identification of activities that provoke angina and the amount of

sublingual nitroglycerin required to relieve symptoms are helpful

indicators of stability.

A decrease in exercise tolerance or an increase

in the need for nitroglycerin suggests that the angina is progressing in

severity or is accelerating

Mechanism of pain syndrome in angina

Common

• Physical exertion

• Cold exposure

• Heavy meals

• Intense emotion

Uncommon

• Lying flat (decubitus

angina)

• Vivid dreams (nocturnal

angina)

17.           Diagnostic algorithm in stable angina. Therapy of stable angina: drugs affecting the quality of life and prognosis.

Diagnostic algorithm in stable angina

Resting ECG

The ECG may show evidence of previous MI but is often

normal, even in patients with severe coronary artery

disease. Occasionally, there is T-wave flattening or

inversion in some leads, providing non-specific evidence

of myocardial ischaemia or damage. The most

convincing ECG evidence of myocardial ischaemia is the

demonstration of reversible ST segment depression or

elevation, with or without T-wave inversion, at the time

the patient is experiencing symptoms (whether spontaneous

or induced by exercise testing).

Exercise ECG

An exercise tolerance test (ETT) is usually performed

using a standard treadmill or bicycle ergometer protocol  while monitoring the patient’s ECG, BP and general condition. Planar or down-sloping ST segment

depression of 1 mm or more is indicative of ischaemia. Up-sloping ST depression is less specific and often occurs in normal individuals.

Exercise testing is also a useful means of assessing the

severity of coronary disease and identifying high-risk

individuals . For example, the amount of

exercise that can be tolerated and the extent and degree

of any ST segment change  provide a useful

guide to the likely extent of coronary disease. Exercise

testing is not infallible and may produce false-positive

results in the presence of digoxin therapy, left ventricular

hypertrophy, bundle branch block or WPW syndrome.

The predictive accuracy of exercise testing is lower in women than in men. The test should be classed as inconclusive (rather than negative) if the patient

cannot achieve an adequate level of exercise because of

locomotor or other non-cardiac problems.

Other forms of stress testing

• Myocardial perfusion scanning. This may be helpful in

the evaluation of patients with an equivocal or

uninterpretable exercise test and those who are

unable to exercise . It entails obtaining

scintiscans of the myocardium at rest and during

stress (either exercise testing or pharmacological

stress, such as a controlled infusion of dobutamine),

after the administration of an intravenous

radioactive isotope, such as technetium

tetrofosmin. Thallium and tetrofosmin are taken up

by viable perfused myocardium. A perfusion defect

present during stress but not at rest provides

evidence of reversible myocardial ischaemia

, whereas a persistent perfusion defect

seen during both phases of the study is usually

indicative of previous MI.

• Stress echocardiography. This is an alternative to

myocardial perfusion scanning and can achieve

similar predictive accuracy. It uses transthoracic

echocardiography to identify ischaemic segments of

myocardium and areas of infarction (p. 537). The

former characteristically exhibit reversible defects in

contractility during exercise or pharmacological

stress, and the latter do not contract at rest or

during stress.

Coronary arteriography

This provides detailed anatomical information about

the extent and nature of coronary artery disease (see

Fig. 18.15, p. 538), and is usually performed with a

view to coronary artery bypass graft (CABG) surgery or

percutaneous coronary intervention (PCI) (pp. 587 and

588). In some patients, diagnostic coronary angiography

may be indicated when non-invasive tests have failed to

establish the cause of atypical chest pain. The procedure

is performed under local anaesthesia and requires specialised

radiological equipment, cardiac monitoring and

an experienced operating team

18.           Unstable angina (UA). Classification of UA by Braunwald. Instrumental and laboratory methods of investigations for establish the diagnosis.

Angina that changes in intensity, character or frequency is termed unstable. Signs of unstable angina are pains at rest, a marked increase in the frequency of attacks, discomfort that occurs with minimal activity, and new-onset angina of incapacitating severity. Unstable angina usually is related to the rupture of an atherosclerotic plaque and the abrupt narrowing or occlusion of a coronary artery, representing a medical emergency. Unstable angina may precede myocardial infarction, and requires urgent medical attention. It is treated with oxygen, intravenous nitroglycerin, and morphine. Interventional procedures such as angioplasty may be done.

In angina patients momentarily not feeling any chest pain, an electrocardiogram (ECG) is typically normal, unless there have been other cardiac problems in the past. During periods of pain, depression, or elevation of the ST segment may be observed. To elicit these changes, an exercise ECG test (“treadmill test”) may be performed, during which the patient exercises to his/her maximum ability before fatigue, breathlessness, or pain intervenes; if characteristic ECG changes are documented (typically more than 1 mm of flat or downsloping ST depression), the test is considered diagnostic for angina. Even constant monitoring of the blood pressure and the pulse rate can lead us to some conclusion regarding the angina. The exercise test is also useful in looking for other markers of myocardial ischaemia: blood pressure response (or lack thereof, in particular a drop in systolic pressure), dysrhythmia and chronotropic response. Other alternatives to a standard exercise test include a thallium scintigram or sestamibi scintigram (in patients unable to exercise enough for the purposes of the treadmill tests, e.g., due to asthma or arthritis or in whom the ECG is too abnormal at rest) or Stress Echocardiography.
In patients in whom such noninvasive testing is diagnostic, a coronary angiogram is typically performed to identify the nature of the coronary lesion, and whether this would be a candidate for angioplasty, coronary artery bypass graft (CABG), treatment only with medication, or other treatments. There has been research that concludes that a frequency is attained when there is increase in the blood pressure and the pulse rate. This frequency varies normally but the range is 45–50 kHz for the cardiac arrest or for the heart failure. In patients in hospital with unstable angina (or the newer term of “high-risk acute coronary syndromes”), those with resting ischaemic ECG changes or those with raised cardiac enzymes such as troponin may undergo coronary angiography directly.

19.           Treatment of unstable angina.

Therapy.

First Aid

1, Aspirin 325 mg or/and clopidogrel 300-600mg (Chewing and swallowing)

2, Any Beta-blocker

3, Morphine (IV) start from 1mg and increase. ( it’s the drug of choice because it depress the respiratory center and allows, slow and deep breathing).

      Nitric oxide can also be used in place of morphine

Therapy depends on S-T elevation and non S-T elevation

a.  S-T elevation (within 12 hours of occurrence): Thrombolysis or PCI. Thrombolysis is preferable within the first 2 hours.

b.  No S-T elevation (unstable angina) or S-T elevation After 12 hours: Estimation of GRACE score, if the patient has more than 140 you treat as patient with S-T elevation. Less than 140 treat conservatively.

Conservative Treatment

Nitroglycerin (to stimulate opening of collaterals). Intravenously on the first day.

Beta-blockers

Statins

Antiplatelet drug

Anti-coagulant drugs (first day Heparin IV, from second day isoforms of heparin subcutaneously.

20.           Acute coronary syndrome (ACS). Definition, classification. Pathogenesis.

21.           Management of Acute coronary syndrome depending on type.

Therapy.

First Aid

1, Aspirin 325 mg or/and clopidogrel 300-600mg (Chewing and swallowing)

2, Any Beta-blocker

3, Morphine (IV) start from 1mg and increase. ( it’s the drug of choice because it depress the respiratory center and allows, slow and deep breathing).

      Nitric oxide can also be used in place of morphine

Therapy depends on S-T elevation and non S-T elevation

a.  S-T elevation (within 12 hours of occurrence): Thrombolysis or PCI. Thrombolysis is preferable within the first 2 hours.

b.  No S-T elevation or S-T elevation After 12 hours: Estimation of GRACE score, if the patient has more than 140 you treat as patient with S-T elevation. Less than 140 treat conservatively.

Conservative Treatment

Nitroglycerin (to stimulate opening of collaterals). Intravenously on the first day.

Beta-blockers

Statins

Antiplatelet drug

Anti-coagulant drugs (first day Heparin IV, from second day isoforms of heparin subcutaneously.

22.           Myocardial infarction. Etiology. Pathogenesis. Classifications of MI.

23.           Clinical picture of acute myocardial infarction. Clinical variants of MI.

24.           ECG and laboratory diagnosis of MI. Therapy.

ST depression horizontal or oblique more than 1mm for limb     

                         Leads and more than 2mm for chest leads

                         Indicates ischaemia

T wave tall and sharp indicates subendocardial ischaemia

ST elevation in two neighboring leads

                     More than 1mm for limb leads

                     More than 2mm for chest leads

Q wave wider than 0.03 secs i.e 1/4^th of R wave and deeper than

              1mm in 2 neighboring leads

Therapy.

First Aid

1, Aspirin 325 mg or/and clopidogrel 300-600mg (Chewing and swallowing)

2, Any Beta-blocker

3, Morphine (IV) start from 1mg and increase. ( it’s the drug of choice because it depress the respiratory center and allows, slow and deep breathing).

      Nitric oxide can also be used in place of morphine

Therapy depends on S-T elevation and non S-T elevation

a.  S-T elevation (within 12 hours of occurrence): Thrombolysis or PCI. Thrombolysis is preferable within the first 2 hours.

b.  No S-T elevation or S-T elevation After 12 hours: Estimation of GRACE score, if the patient has more than 140 you treat as patient with S-T elevation. Less than 140 treat conservatively.

Conservative Treatment

Nitroglycerin (to stimulate opening of collaterals). Intravenously on the first day.

Beta-blockers

Statins

Antiplatelet drug

Anti-coagulant drugs (first day Heparin IV, from second day isoforms of heparin subcutaneously.

25.           Complications of myocardial infarction, cardiogenic shock. The principles of treatment.

 26.           Complications of myocardial infarction: acute left ventricular failure (Cardiac asthma, lung edema). The principles of treatment.

27.           Complications of myocardial infarction: acute and chronic cardiac aneurysm, rupture of the heart, Dressler syndrome. Therapeutic tactics.

28.           Myocardial infarction. Treatment: pain relief, reperfusion infarct-related artery, limitation of ischemic damage to the area.

29.           Modern concepts on the pathogenesis of arrhythmias. Classification of arrhythmias and problems with conduction.

pathogenesis

1. Increased automaticity: The tachycardia is produced

by repeated spontaneous depolarisation of an

ectopic focus, often in response to catecholamines.

2. Re-entry: The tachycardia is initiated by an ectopic beat and sustained by a re-entry circuit

Most tachyarrhythmias are due to re-entry.

3. Post depolarization: This can cause ventricular

arrhythmias in patients with coronary artery

disease. It is a form of secondary depolarisation

arising from an incompletely repolarised cell

membrane.

 Classification

SVT – supraventricular tachycardia

PAC – premature atrial contraction

PVC – premature ventricular contraction 

30.           Clinical manifestations of arrhythmias and blockades. Methods of diagnosis.

31.           Clinical manifestations and diagnostic methods in patients with extrasystoles (premature beats), paroxysmal tachycardias.

32.           The treatment of patients with extrasystoles (premature beats), paroxysmal tachycardias.

Management in paroxysmal
tachycardias

Vagal maneuvers e.g carotid sinus massage

IV adenosine

IV verapamil/diltiazem

If there is no termination

IV ibutilide + AV nodal–blocking agent

IV procainamide + AV nodal–blocking agent cardioversion

33.           Clinical manifestations, diagnostic methods in cases with fibrillation (atrial and ventricular).

34.           The etiology, clinical manifestation, diagnostic methods, principles of treatment of sick sinus syndrome (sinoatrial disease).

Clinical characteristics of sick sinus
syndrome

Symptoms associated with SA node dysfunction, in particular tachycardia-bradycardia syndrome, may be related to both slow and fast heart rates. For example, tachycardia may be associated with palpitations, angina pectoris, and heart failure, and bradycardia maynbe associated with hypotension, syncope, presyncope, fatigue, and weakness. In the setting of SSS, overdrive suppression of the SA node may result in prolonged pauses and syncope upon termination of the tachycardia. In many cases, symptoms associated with SA node dysfunction result from concomitant cardiovascular disease. A significant minority of patients with SSS develop signs and symptoms of heart failure that may be related to slow or fast heart rates.

diagnostic methods

SA node dysfunction is most commonly a clinical or electrocardiographic

diagnosis. Sinus bradycardia or pauses on the resting ECG

are rarely sufficient to diagnose SA node disease, and longer-term

recording and symptom correlation generally are required. Symptoms

in the absence of sinus bradyarrhythmias may be sufficient to exclude

a diagnosis of SA node dysfunction.

Management of sick sinus
syndrome.

Since SA node dysfunction is not associated with increased mortality rates, the aim of therapy is alleviation of symptoms. Exclusion of extrinsic causes of SA node dysfunction and correlation of the cardiac rhythm with symptoms is an essential part of patient management.

   Pacemaker implantation is the primary therapeutic intervention in patients with symptomatic SA node dysfunction.

   Stopping the usage of drugs like beta blockers, calcium channel blockers, class I and III anti arrrthymic drugs that can increase sa nodal dysfunction.

Isoproterenol, atropine, Theophylline

administered IV may increase the sinus rate Theophylline

Digitalis can be used to shorten the s.a node refractory time.

35.           Problems with conduction. Classification. Clinical and ECG manifestations.

36.           Treatment of blockades (problems with conduction).

37.           Etiology, pathogenesis of chronic heart failure.

Etiology

> Heart failure: causes HEART FAILED:
Hypertension
Endocrine
Anemia
Rheumatic heart disease
Toxins
Failure to take meds
Arrythmia
Infection
Lung (PE, pneumonia)
Electrolytes
Diet

Pathogenesis

The understanding of the pathophysiology of heart failure has evolved significantly over the last decades, from the haemodynamic model to the neurohormonal paradigm. Heart failure represents a complex syndrome in which an initial myocardial insult results in the over-expression of multiple peptides with different short- and long-term effects on the cardiovascular system. Neurohormonal activation is recognised to play a pivotal role in the development as well as the progression of heart failure. In the acute phase, neurohormonal activation seems to be beneficial in terms of maintaining adequate cardiac output and peripheral perfusion. Sustained neurohormonal activation, however, eventually results in increased wall stress, dilation, and ventricular remodelling, which contribute to disease progression in the failing myocardium, which eventually leads to further neurohormonal activation. Left ventricular remodelling is the process by which mechanical, neurohormonal, and possibly genetic factors alter ventricular size, shape, and function. Remodelling occurs in several clinical conditions, including MI, cardiomyopathy, hypertension, and valvular heart disease; its hallmarks include hypertrophy, loss of myocytes, and increased interstitial fibrosis. One potential deleterious outcome of remodelling, as the left ventricle dilates and the heart assumes a more globular shape, is the development of mitral regurgitation. Mitral regurgitation results in an increasing volume overload on the overburdened left ventricle that further contributes to remodelling and progression of disease and symptoms.

38.           Classification of chronic heart failure according to stages and functional classes (NYHA and AHA/ACC).

Classification

Classification of Patients by the American Heart Association /American College of Cardiologist Stages of Heart Failure

Stage	Description
No real HF	A	Patients at high risk of developing HF because of the presence of conditions that are strongly associated with the development of HF. Such patients have no identified structural or functional abnormalities of the pericardium, myocardium, or cardiac valves and have never shown signs or symptoms of HF.
	B	Patients who have developed structural heart disease that is strongly associated with the development of HF but who have never shown signs or symptoms of HF.
C	Patients who have current or prior symptoms of HF associated with underlying structural heart disease.
D	Patients with advanced structural heart disease and marked symptoms of HF at rest despite maximal medical therapy and who require specialized interventions.

Classification of severity in heart failure

The New York Heart Association (NYHA) classification of CHF is the most widely used means to classify the severity of symptoms.

Class I      No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, or dyspnea.*

Class II    Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity results in fatigue, palpitation, or

dyspnea

Class III    Marked limitation of physical activity. Comfortable at rest, but less than ordinary activity causes fatigue, palpitation, or dyspnea.

Class IV   Unable to carry out any physical activity without discomfort. Symptoms of cardiac insufficiency at rest. If any physical activity is undertaken, discomfort is increased.

39.            Methods of investigations of chronic heart failure. Non-pharmacological treatment.

Diagnosis

Serum urea, creatinine and electrolytes, haemoglobin, thyroid function, ECG and chest X-ray, Brain natriuretic peptide (BNP), Echocardiography, CT, MRI, Coronary angiogram.

Nonmedicamental therapy

• Education of patients

• Weight monitoring

• Dietary measures (Sodium, Fluids, Alcohol)

• Limitation of physical activity

40.           Medicament therapy of chronic heart failure depending on the disease stage.

 STAGE A

Primary methods:

- Treat hypertension

- Encourage smoking cessation

- Treat lipid disorders

- Encourage regular exercise

- Discourage alcohol intake, illicit drug use

               

Additional drugs

- ACEI in appropriate patients for vascular disease or

Diabetes

STAGE B

Primary methods:

- All measures under Stage A

Additional drugs

- ACEI in all patients with reduced left ventricle

ejection fraction even with no HF symptoms

- Beta-blockers in all patients with a recent or remote

history of MI regardless of ejection fraction or presence

of CHF

STAGE C

Primary methods:

-All measures under Stage A and B

-Dietary salt restriction

DRUGS FOR ROUTINE USE

- Diuretics for fluid retention - ACEI - Beta-blockers

DRUGS IN SELECTED PATIENTS

-Aldosterone antagonist - ARBs - Digitalis

- Hydralazine/Nitrates

DEVICES IN SELECTED PATIENTS

-Biventricular pacing -Implantable defibrillators

STAGE D

Primary methods:

- All measures under Stage A, B, C

ADDITIONAL OPTIONS

- Compassionate end–oflife care/hospice

- Extraordinary measures

• heart transplant

• chronic inotropes

• permanent mechanical support

• experimental surgery or drugs