Definition, Types, Risk factors, Pathogenesis, Complications, Diagnosis and Treatment of Hypertension

 Definition, Types, Risk factors, Pathogenesis, Complications, Diagnosis and Treatment of Hypertension .

DEFINITIONS:

Normal blood pressure – Systolic <120 mmHg and diastolic <80 mmHg

Elevated blood pressure – Systolic 120 to 129 mmHg and diastolic <80 mmHg

Stage 1 Hypertension – Systolic 130 to 139 mmHg or diastolic 80 to 89 mmHg

Stage 2 Hypertension – Systolic at least 140 mmHg or diastolic at least 90 mmHg

Types of Hypertension:

PRIMARY HYPERTENSION:

Hypertension without any know cause is called primary Hypertension. 

Risk factors for primary (essential) hypertension:

●Age – Advancing age is associated with increased blood pressure, particularly systolic blood pressure, and an increased incidence of hypertension.

●Obesity – Obesity and weight gain are major risk factors for hypertension and are also determinants of the rise in blood pressure that is commonly observed with aging.

●Family history – Hypertension is approximately twice as common in subjects who have one or two hypertensive parents, and multiple epidemiologic studies suggest that genetic factors account for approximately 30 percent of the variation in blood pressure in various populations.

●Race – Hypertension tends to be more common, be more severe, occur earlier in life, and be associated with greater target-organ damage in Black patients.

●Reduced nephron number – Reduced adult nephron mass may predispose to hypertension, which may be related to genetic factors, intrauterine developmental disturbance (eg, hypoxia, drugs, nutritional deficiency), premature birth, and postnatal environment (eg, malnutrition, infections).

●High-sodium diet – Excess sodium intake (eg, >3 g/day [sodium chloride]) increases the risk for hypertension, and sodium restriction lowers blood pressure in those with a high sodium intake.

●Excessive alcohol consumption – Excess alcohol intake is associated with the development of hypertension, and alcohol restriction lowers blood pressure in those with increased intake.

●Physical inactivity – Physical inactivity increases the risk for hypertension, and exercise (aerobic, dynamic resistance, and isometric resistance) is an effective means of lowering blood pressure.

●Insufficient sleep – Short sleep duration (eg, <7 hours per night) is associated with a higher risk of hypertension [21-23], and increasing the duration of sleep may lower blood pressure.

●Social determinants – Social determinants of health, such as low socioeconomic status, lack of health insurance, food and housing insecurity, and lack of access to safe spaces for exercise may underlie several of the above risk factors for hypertension (obesity, poor diet, physical inactivity, etc. These social factors likely account in large part for racial disparities in hypertension.

SECONDARY OR CONTRIBUTING CAUSES OF HYPERTENSION:

Hypertension with know cause is called secondary hypertension. 

Major causes of secondary hypertension include:

manifestations of Cushing syndrome".)

●Oral contraceptives, particularly those containing higher doses of estrogen

•Nonsteroidal antiinflammatory agents (NSAIDs), particularly chronic use 

●Antidepressants, including tricyclic antidepressants, selective serotonin reuptake inhibitors, and monoamine oxidase inhibitors

•Corticosteroids, including both glucocorticoids and mineralocorticoids

•Decongestants, such as phenylephrine and pseudoephedrine

•Some weight-loss medications

•Sodium-containing antacids

•Erythropoietin

•Cyclosporine or tacrolimus

•Stimulants, including methylphenidate and amphetamines

•Atypical antipsychotics, including clozapine and olanzapine

•Angiogenesis inhibitors, such as bevacizumab

•Tyrosine kinase inhibitors, such as sunitinib and sorafenib

●Illicit drug use – Drugs such as methamphetamines and cocaine can raise blood pressure.

●Primary kidney disease – Both acute and chronic kidney disease can lead to hypertension. 

●Primary aldosteronism – The presence of primary mineralocorticoid excess, primarily aldosterone, should be suspected in any patient with the triad of hypertension, unexplained hypokalemia, and metabolic alkalosis. However, up to 50 to 70 percent of patients will have a normal plasma potassium concentration. Other disorders or ingestions can mimic primary aldosteronism (apparent mineralocorticoid excess syndromes), including chronic licorice intake.

●Renovascular hypertension – Renovascular hypertension is often due to fibromuscular dysplasia in younger patients and to atherosclerosis in older patients. 

●Obstructive sleep apnea – Disordered breathing during sleep appears to be an independent risk factor for systemic hypertension.

●Pheochromocytoma – Pheochromocytoma is a rare cause of secondary hypertension. Approximately one-half of patients with pheochromocytoma have paroxysmal hypertension; most of the rest have what appears to be primary hypertension.

●Cushing's syndrome – Cushing's syndrome is a rare cause of secondary hypertension, but hypertension is a major cause of morbidity and death in patients with Cushing's syndrome.

●Other endocrine disorders – Hypothyroidism, hyperthyroidism, and hyperparathyroidism may also induce hypertension.

●Coarctation of the aorta – Coarctation of the aorta is one of the major causes of secondary hypertension in young children, but it may also be diagnosed in adulthood.

Symptoms:

severe headaches

chest pain

dizziness

difficulty breathing

nausea

vomiting

blurred vision or other vision changes

anxiety

confusion

buzzing in the ears

nosebleeds

abnormal heart rhythm

COMPLICATIONS OF HYPERTENSION:

●Left ventricular hypertrophy (LVH)

●Heart failure, both reduced ejection fraction (systolic) and preserved ejection fraction (diastolic) 

●Ischemic stroke

●Intracerebral hemorrhage

●Ischemic heart disease, including myocardial infarction and coronary interventions

●Chronic kidney disease and end-stage kidney disease 

DIAGNOSIS OF HYPERTENSION:

Classification Systolic and diastolic readings

●Normal systolic: less than 120 mm Hg

diastolic: less than 80 mm Hg

●Elevated systolic: 120–129 mm Hg

diastolic: less than 80 mm Hg

●High blood pressure systolic: 130 mm Hg or higher

diastolic: 80 mm Hg or higher

Laboratory testing:

●Electrolytes (including calcium) and serum creatinine (to calculate the estimated glomerular filtration rate)

●Fasting glucose

●Urinalysis

●Complete blood count

●Thyroid-stimulating hormone

●Lipid profile

●Electrocardiogram

●Calculate 10-year atherosclerotic cardiovascular disease risk

TREATMENT:

Nonpharmacologic therapy:

●Dietary salt restriction – In well-controlled randomized trials, the overall impact of moderate sodium reduction is a fall in blood pressure in hypertensive and normotensive individuals of 4.8/2.5 and 1.9/1.1 mmHg, respectively. The effects of sodium restriction on blood pressure, cardiovascular disease, and mortality as well as specific recommendations for sodium intake, are discussed in detail elsewhere.

●Potassium supplementation, preferably by dietary modification, unless contraindicated by the presence of chronic kidney disease or use of drugs that reduce potassium excretion.

●Weight loss – Weight loss in overweight or obese individuals can lead to a significant fall in blood pressure independent of exercise. The decline in blood pressure induced by weight loss can also occur in the absence of dietary sodium restriction [53], but even modest sodium restriction may produce an additive antihypertensive effect. The weight loss-induced decline in blood pressure generally ranges from 0.5 to 2 mmHg for every 1 kg of weight lost.

●DASH diet – The Dietary Approaches to Stop Hypertension (DASH) dietary pattern is high in vegetables, fruits, low-fat dairy products, whole grains, poultry, fish, and nuts and low in sweets, sugar-sweetened beverages, and red meats. The DASH dietary pattern is consequently rich in potassium, magnesium, calcium, protein, and fiber but low in saturated fat, total fat, and cholesterol. A trial in which all food was supplied to normotensive or mildly hypertensive adults found that the DASH dietary pattern reduced blood pressure by 6/4 mmHg compared with a typical American-style diet that contained the same amount of sodium and the same number of calories. Combining the DASH dietary pattern with modest sodium restriction produced an additive antihypertensive effect. These trials and a review of diet in the treatment of hypertension are discussed in detail elsewhere.

●Exercise – Aerobic, dynamic resistance and isometric resistance exercise can decrease systolic and diastolic pressure by, on average, 4 to 6 mmHg and 3 mmHg, respectively, independent of weight loss. Most studies demonstrating a reduction in blood pressure have employed at least three to four sessions per week of moderate-intensity aerobic exercise lasting approximately 40 minutes for a period of 12 weeks. 

●Limited alcohol intake – Women who consume two or more alcoholic beverages per day and men who have three or more drinks per day have a significantly increased incidence of hypertension compared with nondrinkers. Adult men and women with hypertension should consume, respectively, no more than two and one alcoholic drinks daily.

Pharmacologic therapy:

●Thiazide-like or thiazide-type diuretics

●Long-acting calcium channel blockers (most often a dihydropyridine such as amlodipine)

●Angiotensin-converting enzyme (ACE) inhibitors

●Angiotensin II receptor blockers (ARBs)

Combination therapy:

Single-agent therapy will not adequately control blood pressure in most patients whose baseline systolic blood pressure is 15 mmHg or more above their goal. Combination therapy with drugs from different classes has a substantially greater blood pressure-lowering effect than doubling the dose of a single agent, often with a reduction in side effects seen with a higher dose of monotherapy. When more than one agent is needed to control the blood pressure, we recommend therapy with a long-acting ACE inhibitor or ARB in concert with a long-acting dihydropyridine calcium channel blocker. Combination of an ACE inhibitor or ARB with a thiazide diuretic can also be used but may be less beneficial when hydrochlorothiazide is used. ACE inhibitors and ARBs should not be used together. 

Prevention:

Do:

•Eat more vegetables and fruits.

•Sit less.

•Be more physically active, which can include walking, running, swimming, dancing or activities that build strength, like lifting weights.

•Get at least 150 minutes per week of moderate-intensity aerobic activity or 75 minutes per week of vigorous aerobic activity.

•Do strength building exercises 2 or more days each week.

•Lose weight if you’re overweight or obese.

•Take medicines as prescribed by your health care professional.

•Keep appointments with your health care professional.

Don’t:

•Eat too much salty food (try to stay under 2 grams per day)

•Eat foods high in saturated or trans fats

•Smoke or use tobacco

•Drink too much alcohol (1 drink daily max for women, 2 for men)

•Miss or share medication.

Pathogenesis, Clinical features, Diagnosis, and Management of Community Acquired Pneumonia

 INTRODUCTION:

Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality worldwide. The clinical presentation of CAP varies, ranging from mild pneumonia characterized by fever and productive cough to severe pneumonia characterized by respiratory distress and sepsis. Because of the wide spectrum of associated clinical features, CAP is a part of the differential diagnosis of nearly all respiratory illnesses.

DEFINITIONS:

Community-acquired pneumonia (CAP) refers to an acute infection of the pulmonary parenchyma acquired outside of the hospital.

●Nosocomial pneumonia refers to an acute infection of the pulmonary parenchyma acquired in hospital settings and encompasses both hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP).

•HAP refers to pneumonia acquired ≥48 hours after hospital admission.

•VAP refers to pneumonia acquired ≥48 hours after endotracheal intubation.

Risk factors:

Older age – The risk of CAP rises with age. The annual incidence of hospitalization for CAP among adults ≥65 years old is approximately 2000 per 100,000 in the United States. This figure is approximately three times higher than the general population and indicates that 2 percent of the older adult population will be hospitalized for CAP annually .

Chronic comorbidities – The comorbidity that places patients at highest risk for CAP hospitalization is chronic obstructive pulmonary disease (COPD), with an annual incidence of 5832 per 100,000 in the United States [7]. Other comorbidities associated with an increased incidence of CAP include other forms of chronic lung disease (eg, bronchiectasis, asthma), chronic heart disease (particularly congestive heart failure), stroke, diabetes mellitus, malnutrition, and immunocompromising conditions.

Viral respiratory tract infection – Viral respiratory tract infections can lead to primary viral pneumonias and also predispose to secondary bacterial pneumonia. This is most pronounced for influenza virus infection.

Impaired airway protection – Conditions that increase risk of macroaspiration of stomach contents and/or microaspiration of upper airway secretions predispose to CAP, such as alteration in consciousness (eg, due to stroke, seizure, anesthesia, drug or alcohol use) or dysphagia due to esophageal lesions or dysmotility.

Smoking and alcohol overuse – Smoking, alcohol overuse (eg, >80 g/day), and opioid use are key modifiable behavioral risk factors for CAP.

Other lifestyle factors – Other factors that have been associated with an increased risk of CAP include crowded living conditions (eg, prisons, homeless shelters), residence in low-income settings, and exposure to environmental toxins (eg, solvents, paints, or gasoline).

MICROBIOLOGY:

Common causes — Streptococcus pneumoniae (pneumococcus) and respiratory viruses are the most frequently detected pathogens in patients with CAP.

The most commonly identified causes of CAP can be grouped into three categories:

●Typical bacteria

•S. pneumoniae (most common bacterial cause)

•Haemophilus influenzae

•Moraxella catarrhalis

•Staphylococcus aureus

•Group A streptococci

•Aerobic gram-negative bacteria (eg, Enterobacteriaceae such as Klebsiella spp or Escherichia coli)

•Microaerophilic bacteria and anaerobes (associated with aspiration)

●Atypical bacteria ("atypical" refers to the intrinsic resistance of these organisms to beta-lactams and their inability to be visualized on Gram stain or cultured using traditional techniques)

•Legionella spp

•Mycoplasma pneumoniae

•Chlamydia pneumoniae

•Chlamydia psittaci

•Coxiella burnetii

●Respiratory viruses

•Influenza A and B viruses

•Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

•Other coronaviruses (eg, CoV-229E, CoV-NL63, CoV-OC43, CoV-HKU1)

•Rhinoviruses

•Parainfluenza viruses

•Adenoviruses

•Respiratory syncytial virus

•Human metapneumovirus

•Human bocaviruses

PATHOGENESIS:

CAP has been viewed as an infection of the lung parenchyma, primarily caused by bacterial or viral respiratory pathogens. In this model, respiratory pathogens are transmitted from person to person via droplets or, less commonly, via aerosol inhalation (eg, as with Legionella or Coxiella species). Following inhalation, the pathogen colonizes the nasopharynx and then reaches the lung alveoli via microaspiration. When the inoculum size is sufficient and/or host immune defenses are impaired, infection results. Replication of the pathogen, the production of virulence factors, and the host immune response lead to inflammation and damage of the lung parenchyma, resulting in pneumonia (figure 3).

With the identification of the lung microbiome, that model has changed [19-21]. While the pathogenesis of pneumonia may still involve the introduction of respiratory pathogens into the alveoli, the infecting pathogen likely has to compete with resident microbes to replicate. In addition, resident microbes may also influence or modulate the host immune response to the infecting pathogen. If this is correct, an altered alveolar microbiome (alveolar dysbiosis) may be a predisposing factor for the development of pneumonia.

In some cases, CAP might also arise from uncontrolled replication of microbes that normally reside in the alveoli. The alveolar microbiome is similar to oral flora and is primarily comprised of anaerobic bacteria (eg, Prevotella and Veillonella) and microaerophilic streptococci. Hypothetically, exogenous insults such as a viral infection or smoke exposure might alter the composition of the alveolar microbiome and trigger overgrowth of certain microbes. Because organisms that compose the alveolar microbiome typically cannot be cultivated using standard cultures, this hypothesis might explain the low rate of pathogen detection among patients with CAP.

In any scenario, the host immune response to microbial replication within the alveoli plays an important role in determining disease severity. For some patients, a local inflammatory response within the lung predominates and may be sufficient for controlling infection. In others, a systemic response is necessary to control infection and to prevent spread or complications, such as bacteremia. In a minority, the systemic response can become dysregulated, leading to tissue injury, sepsis, acute respiratory distress syndrome, and/or multiorgan dysfunction.

CLINICAL PRESENTATION:

The clinical presentation of CAP varies widely, ranging from mild pneumonia characterized by fever, cough, and shortness of breath to severe pneumonia characterized by sepsis and respiratory distress. Symptom severity is directly related to the intensity of the local and systemic immune response in each patient.

●Pulmonary signs and symptoms – Cough (with or without sputum production), dyspnea, and pleuritic chest pain are among the most common symptoms associated with CAP. Signs of pneumonia on physical examination include tachypnea, increased work of breathing, and adventitious breath sounds, including rales/crackles and rhonchi. Tactile fremitus, egophony, and dullness to percussion also suggest pneumonia. These signs and symptoms result from the accumulation of white blood cells (WBCs), fluid, and proteins in the alveolar space. Hypoxemia can result from the subsequent impairment of alveolar gas exchange. On chest radiograph, accumulation of WBCs and fluid within the alveoli appears as pulmonary opacities.

●Systemic signs and symptoms – The great majority of patients with CAP present with fever. Other systemic symptoms such as chills, fatigue, malaise, chest pain (which may be pleuritic), and anorexia are also common. Tachycardia, leukocytosis with a leftward shift, or leukopenia are also findings that are mediated by the systemic inflammatory response. Inflammatory markers, such as the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and procalcitonin may rise, though the latter is largely specific to bacterial infections. CAP is also the leading cause of sepsis; thus, the initial presentation may be characterized by hypotension, altered mental status, and other signs of organ dysfunction such as renal dysfunction, liver dysfunction, and/or thrombocytopenia.

Diagnosis:

A chest X-ray looks for inflammation in your lungs. A chest X-ray is often used to diagnose pneumonia.

Blood tests, such as a complete blood count (CBC) see whether your immune system is fighting an infection.

Pulse oximetry measures how much oxygen is in your blood. Pneumonia can keep your lungs from getting enough oxygen into your blood. To measure the levels, a small sensor called a pulse oximeter is attached to your finger or ear.

A blood gas test may be done if you are very sick. For this test, your provider measures your blood oxygen levels using a blood sample from an artery, usually in your wrist. This is called an arterial blood gas test.

A sputum test, using a sample of sputum (spit) or mucus from your cough, may be used to find out what germ is causing your pneumonia.

A blood culture test can identify the germ causing your pneumonia and also show whether a bacterial infection has spread to your blood.

A polymerase chain reaction (PCR) test quickly checks your blood or sputum sample to find the DNA of germs that cause pneumonia.

A bronchoscopy looks inside your airways. If your treatment is not working well, this procedure may be needed. At the same time, your doctor may also collect samples of your lung tissue and fluid from your lungs to help find the cause of your pneumonia.

A chest computed tomography (CT) scan can show how much of your lungs are affected by pneumonia. It can also show whether you have complications such as lung abscesses or pleural disorders. A CT scan shows more detail than a chest X-ray.

A pleural fluid culture can be taken using a procedure called thoracentesis, which is when a doctor uses a needle to take a sample of fluid from the pleural space between your lungs and chest wall. The fluid is then tested for bacteria.

DIFFERENTIAL DIAGNOSIS:

Congestive heart failure with pulmonary edema

•Pulmonary embolism

•Pulmonary hemorrhage

•Atelectasis

•Aspiration or chemical pneumonitis

•Drug reactions

•Lung cancer

•Collagen vascular diseases

•Vasculitis

•Acute exacerbation of bronchiectasis

•Interstitial lung diseases (eg, sarcoidosis, asbestosis, hypersensitivity pneumonitis, cryptogenic organizing pneumonia)

TREATMENT:

Outpatient antibiotic therapy:

For most patients aged <65 years who are otherwise healthy and have not recently used antibiotics, we typically use oral amoxicillin (1 g three times daily) plus a macrolide (eg, azithromycin or clarithromycin) or doxycycline. Generally, we prefer to use a macrolide over doxycycline.

This approach differs from the American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA), which recommend monotherapy with amoxicillin as first line and monotherapy with either doxycycline or a macrolide (if local resistance rates are <25 percent [eg, not in the United States]) as alternatives for this population [26]. The rationale for each approach is discussed separately. (See "Treatment of community-acquired pneumonia in adults in the outpatient setting", section on 'Empiric antibiotic treatment'.)

●For patients who have major comorbidities (eg, chronic heart, lung, kidney, or liver disease, diabetes mellitus, alcohol dependence, or immunosuppression), who are smokers, and/or who have used antibiotics within the past three months, we suggest oral amoxicillin-clavulanate (875 mg twice daily or extended release 2 g twice daily) plus either a macrolide (preferred) or doxycycline.

Inpatient antibiotic therapy:

For patients without suspicion for MRSA or Pseudomonas, we generally use one of two regimens: combination therapy with a beta-lactam plus a macrolide or monotherapy with a respiratory fluoroquinolone. Because these two regimens have similar clinical efficacy, we select among them based on other factors (eg, antibiotic allergy, drug interactions). For patients who are unable to use either a macrolide or a fluoroquinolone, we use a beta-lactam plus doxycycline.

●For patients with known colonization or prior infection with Pseudomonas, recent hospitalization with IV antibiotic use, or other strong suspicion for pseudomonal infection, we typically use combination therapy with both an antipseudomonal beta-lactam (eg, piperacillin-tazobactam, cefepime, ceftazidime, meropenem, or imipenem) plus an antipseudomonal fluoroquinolone (eg, ciprofloxacin or levofloxacin). The selection of empiric regimens should also be informed by the susceptibility pattern for prior isolates.

●For patients with known colonization or prior infection with MRSA or other strong suspicion for MRSA infection, we add an agent with anti-MRSA activity, such as vancomycin or linezolid, to either of the above regimens. We generally prefer linezolid over vancomycin when community-acquired MRSA is suspected (eg, a young, otherwise healthy patient who plays contact sports presenting with necrotizing pneumonia) because of linezolid's ability to inhibit bacterial toxin production.Ceftaroline is a potential alternative for the treatment of MRSA pneumonia but is not US Food and Drug Administration approved.

PREVENTION:

The three primary pillars for the prevention of CAP are:

●Smoking cessation (when appropriate)

●Influenza vaccination for all patients

●Pneumococcal vaccination for at-risk patients