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Malignant Hypertension

Disease Details

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Description: Malignant hypertension is a severe and rapid increase in blood pressure that can lead to organ damage, particularly of the kidneys, brain, heart, and eyes.
Type: Malignant hypertension is not a disease with a single genetic transmission pattern. It is a severe form of high blood pressure that can involve various underlying factors, including genetic predispositions, lifestyle factors, and other health conditions. The genetic component is complex and multifactorial rather than following a specific type of genetic transmission.
Signs And Symptoms: Symptoms may include headache, nausea, or vomiting. Chest pain may occur due to increased workload on the heart resulting in inadequate delivery of oxygen to meet the heart muscle's metabolic needs. The kidneys may be affected, resulting in blood or protein in the urine, and acute kidney failure. People can have decreased urine production, fluid retention, and confusion.Other signs and symptoms can include:
Chest pain
Abnormal heart rhythms
Headache
Nosebleeds that are difficult to stop
Dyspnea
Fainting or the sensation of the world spinning around them (vertigo)
Severe anxiety
Agitation
Altered mental status
Abnormal sensationsThe most common presentations of hypertensive emergencies are cerebral infarction (24.5%), pulmonary edema (22.5%), hypertensive encephalopathy (16.3%), and congestive heart failure (12%). Less common presentations include intracranial bleeding, aortic dissection, and pre-eclampsia or eclampsia.Massive, rapid elevations in blood pressure can trigger any of these symptoms, and warrant further work-up by physicians. Physical exam would include measurement of blood pressure in both arms. Laboratory tests to be conducted include urine toxicology, blood glucose, a basic metabolic panel evaluating kidney function, or a complete metabolic panel evaluating liver function, EKG, chest x-rays, and pregnancy screening.The eyes may show bleeding in the retina, an exudate, cotton-wool spots, scattered splinter hemorrhages, or swelling of the optic disc called papilledema.
Prognosis: Severe hypertension is a serious and potentially life-threatening medical condition. It is estimated that people who do not receive appropriate treatment only live an average of about three years after the event.The morbidity and mortality of hypertensive emergencies depend on the extent of end-organ dysfunction at the time of presentation and the degree to which blood pressure is controlled afterward. With good blood pressure control and medication compliance, the 5-year survival rate of patients with hypertensive crises approaches 55%.The risks of developing a life-threatening disease affecting the heart or brain increase as the blood flow increases. Commonly, ischemic heart attack and stroke are the causes that lead to death in patients with severe hypertension. It is estimated that for every 20 mm Hg systolic or 10 mm Hg diastolic increase in blood pressures above 115/75 mm Hg, the mortality rate for both ischemic heart disease, cancer and stroke doubles.Consequences of hypertensive emergency result after prolonged elevations in blood pressure and associated end-organ dysfunction. Acute end-organ damage may occur, affecting the neurological, cardiovascular, kidney, or other organ systems. Some examples of neurological damage include hypertensive encephalopathy, cerebral vascular accident/cerebral infarction, subarachnoid hemorrhage, and intracranial bleeding. Cardiovascular system damage can include myocardial ischemia/infarction, acute left ventricular dysfunction, acute pulmonary edema, and aortic dissection. Other end-organ damage can include acute kidney failure or insufficiency, retinopathy, eclampsia, lung cancer, brain cancer, leukemia and microangiopathic hemolytic anemia.
Onset: Malignant hypertension typically has an abrupt onset and is characterized by a sudden and severe increase in blood pressure, often exceeding 180/120 mmHg. It can progress rapidly and requires immediate medical attention to prevent life-threatening complications.
Prevalence: The exact prevalence of malignant hypertension is not well documented due to varying definitions and diagnostic criteria. However, it is considered rare, often developing as a complication in a small percentage of individuals with hypertension.
Epidemiology: In 2000, it was estimated that 1 billion people worldwide have hypertension, making it the most prevalent condition in the world. Approximately 60 million Americans have chronic hypertension, with 1% of these individuals having an episode of hypertensive urgency. In emergency departments and clinics around the U.S., the prevalence of hypertensive urgency is suspected to be between 3-5%. 25% of hypertensive crises have been found to be hypertensive emergency versus urgency when presenting to the ER.Risk factors for hypertensive emergency include age, obesity, noncompliance to anti hypertensive medications, female sex, Caucasian race, preexisting diabetes or coronary artery disease, mental illness, and sedentary lifestyle. Several studies have concluded that African Americans have a greater incidence of hypertension and a greater morbidity and mortality from hypertensive disease than non-Hispanic whites, however hypertensive crises have a greater incidence in Caucasians. Although severe hypertension is more common in the elderly, it may occur in children (though very rarely), likely due to metabolic or hormonal dysfunction. In 2014, a systematic review identified women as having slightly higher increased risks of developing hypertensive crises than do men.With the usage of anti hypertensives, the rates of hypertensive emergencies has declined from 7% to 1% of patients with hypertensive urgency.16% of patients presenting with hypertensive emergency can have no known history of hypertension.
Intractability: Malignant hypertension is a severe and potentially life-threatening condition characterized by extremely high blood pressure that can rapidly lead to organ damage. It is not necessarily intractable, but it does require immediate medical intervention to manage and reduce blood pressure and prevent complications. With prompt and effective treatment, such as intravenous medications and subsequent oral medications, the condition can often be controlled. However, ongoing management and monitoring are crucial to prevent recurrence and manage any underlying conditions.
Disease Severity: Malignant hypertension, also known as hypertensive emergency, is a severe form of high blood pressure that rapidly progresses and can cause significant damage to vital organs. It is typically characterized by blood pressure readings higher than 180/120 mm Hg, along with evidence of acute organ damage, such as hypertensive encephalopathy, retinal hemorrhages, or acute kidney injury. Without prompt and effective treatment, it can be life-threatening.
Healthcare Professionals: Disease Ontology ID - DOID:10824
Pathophysiology: The pathophysiology of hypertensive emergency is not well understood. Failure of normal autoregulation and an abrupt rise in systemic vascular resistance are typical initial components of the disease process.Hypertensive emergency pathophysiology includes:
Abrupt increase in systemic vascular resistance, likely related to humoral vasoconstrictors
Endothelial injury and dysfunction
Fibrinoid necrosis of the arterioles
Deposition of platelets and fibrin
Breakdown of normal autoregulatory functionThe resulting ischemia prompts further release of vasoactive substances including prostaglandins, free radicals, and thrombotic/mitotic growth factors, completing a vicious cycle of inflammatory changes. If the process is not stopped, homeostatic failure begins, leading to loss of cerebral and local autoregulation, organ system ischemia and dysfunction, and myocardial infarction. Single-organ involvement is found in approximately 83% of hypertensive emergency patients, two-organ involvement in about 14% of patients, and multi-organ failure (failure of at least 3 organ systems) in about 3% of patients.In the brain, hypertensive encephalopathy
Carrier Status: Carrier status is not applicable to malignant hypertension, as it is typically not a genetic condition passed down through carriers. Malignant hypertension is a severe and potentially life-threatening condition characterized by extremely high blood pressure that develops rapidly and can cause organ damage. It requires immediate medical attention.
Mechanism: Malignant hypertension, also known as hypertensive emergency, is a severe form of high blood pressure that rapidly progresses and can cause organ damage.

**Mechanism:**

1. **Vascular Injury:** Malignant hypertension causes severe injury to the walls of small blood vessels.
2. **Endothelial Dysfunction:** Elevated blood pressure leads to damage of the endothelium (the inner lining of blood vessels), resulting in increased permeability and further injury.
3. **Ischemia:** Reduced blood flow resulting from damaged vessels leads to tissue ischemia, where organs and tissues receive insufficient oxygen and nutrients.
4. **Activation of Renin-Angiotensin System:** In response to ischemia, the body activates the renin-angiotensin system, which further elevates blood pressure and exacerbates the condition.

**Molecular Mechanisms:**

1. **Oxidative Stress:** Injured endothelial cells produce reactive oxygen species (ROS) that further damage the cells and surrounding tissues.
2. **Inflammatory Cytokines:** Endothelial injury induces the expression of pro-inflammatory cytokines, leading to inflammation and further vascular damage.
3. **Angiotensin II:** This peptide hormone promotes vasoconstriction, sodium retention, and aldosterone release, significantly increasing blood pressure.
4. **Nitric Oxide Disruption:** Normally, nitric oxide produced by the endothelium helps to regulate blood vessel dilation. In malignant hypertension, its production is impaired, leading to unopposed vasoconstriction.
5. **Endothelin:** Increased production of endothelin, a potent vasoconstrictor peptide, contributes to the high blood pressure seen in malignant hypertension.

These mechanisms collectively create a vicious cycle of escalating blood pressure and vascular injury, leading to severe complications such as stroke, heart failure, and kidney damage if not treated promptly.
Treatment: In a hypertensive emergency, treatment should first be to stabilize the patient's airway, breathing, and circulation per ACLS guidelines. Patients should have their blood pressure slowly lowered over a period of minutes to hours with an antihypertensive agent. Documented goals for blood pressure include a reduction in the mean arterial pressure by less than or equal to 25% within the first 8 hours of emergency. If blood pressure is lowered aggressively, patients are at increased risk of complications including stroke, blindness, or kidney failure. Several classes of anti hypertensive agents are recommended, with the choice depending on the cause of the hypertensive crisis, the severity of the elevation in blood pressure, and the patient's baseline blood pressure prior to a hypertensive emergency. Physicians will attempt to identify a cause of the patient's hypertension, including chest radiograph, serum laboratory studies evaluating kidney function, urinalysis, as that will alter the treatment approach for a more patient-directed regimen.Hypertensive emergencies differ from hypertensive urgency in that they are treated parenterally, whereas in urgency it is recommended to use oral anti hypertensives to reduce the risk of hypotensive complications or ischemia. Parenteral agents are classified into beta-blockers, calcium channel blockers, systemic vasodilators, or other (fenoldopam, phentolamine, clonidine). Medications include labetalol, nicardipine, hydralazine, sodium nitroprusside, esmolol, nifedipine, minoxidil, isradipine, clonidine, and chlorpromazine. These medications work through a variety of mechanisms. Labetalol is a beta-blocker with mild alpha antagonism, decreasing the ability of catecholamine activity to increase systemic vascular resistance, while also decreasing heart rate and myocardial oxygen demand. Nicardipine, Nifedipine, and Isradipine are calcium channel blockers that work to decrease systemic vascular resistance and subsequently lower blood pressure. Hydralazine and Sodium nitroprusside are systemic vasodilators, thereby reducing afterload, however can be found to have reflex tachycardia, making them likely second or third line choices. Sodium nitroprusside was previously the first-line choice due to its rapid onset, although now it is less commonly used due to side effects, drastic drops in blood pressure, and cyanide toxicity. Sodium nitroprusside is also contraindicated in patients with myocardial infarction, due to coronary steal. It is again important that the blood pressure is lowered slowly. The initial goal in hypertensive emergencies is to reduce the pressure by no more than 25% the mean arterial pressure. Excessive reduction in blood pressure can precipitate coronary, cerebral, or kidney ischemia and, possibly, infarction.A hypertensive emergency is not based solely on an absolute level of blood pressure, but also on a patient's baseline blood pressure before the hypertensive crisis occurs. Individuals with a history of chronic hypertension may not tolerate a "normal" blood pressure, and can therefore present symptomatically with hypotension, including fatigue, light-headedness, nausea, vomiting, or syncope.
Compassionate Use Treatment: Malignant hypertension is a severe form of high blood pressure that can cause organ damage and is a medical emergency. The main goal in treating this condition is to rapidly lower blood pressure to prevent or limit further damage to organs.

**Compassionate Use Treatment:**
Compassionate use (or expanded access) permits the use of investigational drugs outside of clinical trials for patients with serious or immediately life-threatening conditions who have no comparable or satisfactory alternative therapy options. While there are no specific compassionate use drugs solely for malignant hypertension, medications in this context might be considered when standard treatments are ineffective.

**Off-label or Experimental Treatments:**
1. **Clevidipine:** Although primarily indicated for severe hypertension, Clevidipine may be used off-label in cases of malignant hypertension for its rapid onset and short duration of action.

2. **Sodium Nitroprusside:** Frequently used in critical care for hypertensive emergencies, it can be an off-label choice for malignant hypertension due to its potent vasodilatory properties.

3. **Fenoldopam:** This is another intravenous antihypertensive agent that can be used off-label. It is a dopamine agonist with vasodilatory properties and is effective at lowering blood pressure rapidly.

4. **Urapidil:** Mainly used in Europe for hypertensive emergencies, it has both alpha-1 adrenergic and serotonin receptor antagonistic properties and may be considered in malignant hypertension.

Experimental treatments involving newer antihypertensives or combination therapies are an area of ongoing research but would generally be accessed within a clinical trial setup unless granted through compassionate use pathways. Always consult healthcare providers for the most appropriate treatment options based on individual medical circumstances.
Lifestyle Recommendations: Lifestyle recommendations for managing malignant hypertension include:

1. **Diet**: Adopt a heart-healthy diet rich in fruits, vegetables, whole grains, lean proteins, and low-fat dairy products. Limit sodium, saturated fats, and sugars.
2. **Exercise**: Engage in regular physical activity, such as brisk walking, for at least 30 minutes most days of the week.
3. **Weight Management**: Maintain a healthy weight; losing even a small amount of weight if overweight can significantly reduce blood pressure.
4. **Limit Alcohol**: Drink alcohol in moderation—up to one drink per day for women and two for men.
5. **Quit Smoking**: Avoid tobacco use entirely; smoking can exacerbate high blood pressure and contribute to heart disease.
6. **Stress Management**: Practice stress-reducing techniques like deep breathing, meditation, or yoga.
7. **Medication Adherence**: Ensure consistent use of prescribed medications and regular monitoring of blood pressure.
8. **Regular Check-ups**: Have regular medical check-ups to monitor and manage blood pressure levels effectively.
Medication: For managing malignant hypertension, the medications typically include:

1. **Intravenous Antihypertensives**:
- Sodium nitroprusside
- Labetalol
- Nicardipine
- Fenoldopam
- Esmolol

2. **Oral Antihypertensives** (once initial crisis is controlled):
- ACE inhibitors (e.g., enalapril)
- Beta blockers (e.g., metoprolol)
- Calcium channel blockers (e.g., amlodipine)
- Diuretics (e.g., furosemide)

It is crucial to monitor blood pressure closely and adjust treatment as necessary.
Repurposable Drugs: For malignant hypertension, repurposable drugs can include:

1. **Hydralazine** - A vasodilator that can help to lower blood pressure.
2. **Labetalol** - A combined alpha and beta-blocker that is often used in hypertensive emergencies.
3. **Nitroprusside** - A potent vasodilator used intravenously to rapidly reduce blood pressure.
4. **Clonidine** - An alpha-2 adrenergic agonist that decreases heart rate and relaxes blood vessels.

These medications were originally developed for other applications but can be effective in managing malignant hypertension.
Metabolites: Malignant hypertension, a severe form of high blood pressure, can be associated with various metabolic alterations. Commonly affected metabolites include:

1. **Renin**: Elevated levels due to renal ischemia.
2. **Angiotensin II**: Increased due to heightened renin activity.
3. **Aldosterone**: Often elevated, promoting sodium retention.
4. **Catecholamines**: May be increased, causing vasoconstriction.
5. **Creatinine**: Elevated due to renal impairment.
6. **Urea**: Increased due to decreased renal function.

These changes reflect the body's response to extreme blood pressure elevations and the subsequent end-organ damage.
Nutraceuticals: There are currently no widely recognized nutraceuticals specifically endorsed for the treatment of malignant hypertension. Malignant hypertension is a medical emergency that requires immediate medical intervention, typically involving intravenous antihypertensive medications. Nutraceuticals, generally being dietary supplements, do not provide the rapid and controlled blood pressure reduction needed in this condition. Always consult healthcare professionals for appropriate treatment.
Peptides: Malignant hypertension, also known as a hypertensive crisis, is a severe form of high blood pressure that can cause damage to organs. Treatment typically involves aggressive blood pressure control, though the document doesn't specify peptides as part of the treatment protocol for this condition. Nan, or nanotechnology, is not currently referenced for direct treatment or management of malignant hypertension in standard medical practice.