Cardiovascular System Disorders

Overview and Anatomy of the Cardiovascular System

• Circulatory System Components

  • Vessels: Arteries, arterioles, capillaries, venules, and veins that transport blood throughout the body.

  • Fluid: Blood carrying oxygen, nutrients, cellular waste products, and hormones.

  • Pump: The heart, which provides the necessary pressure to propel blood through the systemic and pulmonary circuits.

  • Circulation Route: Blood moves continuously from systemic circulation through the heart to pulmonary circulation for gas exchange, and returns back to systemic circulation.

• Anatomical Location and Heart Linings

  • Location: Situated within the mediastinum of the thoracic cavity.

  • Endocardium: The innermost smooth endothelial lining that covers the heart chambers and valves.

  • Myocardium: The thick, muscular middle layer responsible for cardiac contraction.

  • Pericardium: The outer protective sac surrounding the heart, consisting of parietal and visceral layers.

  • Pericardial Sac: Contains a thin layer of pericardial fluid to reduce friction during cardiac contractions.

• Heart Chambers and Structures

  • Chambers: Divided into four distinct functional muscular chambers:

  • Right Atrium (RA)

  • Right Ventricle (RV)

  • Left Atrium (LA)

  • Left Ventricle (LV)

  • Septum: A thick muscular wall separating the left and right sides of the heart, preventing the mixing of oxygenated and deoxygenated blood.

• Heart Valves

  • Atrioventricular (AV) Valves: Prevent backflow of blood from the ventricles into the atria during ventricular systole.

  • Tricuspid Valve (TV): Located between the right atrium and right ventricle.

  • Mitral Valve (MV) / Bicuspid Valve: Located between the left atrium and left ventricle.

  • Semilunar Valves: Prevent backflow of blood from the major arteries into the ventricles during ventricular diastole.

  • Pulmonic Valve (PV): Positioned between the right ventricle and the pulmonary artery (located behind adjacent anterior structures).

  • Aortic Valve (AV): Positioned between the left ventricle and the ascending aorta (located behind adjacent anterior structures).

• Sequential Blood Flow Pathway

  • Superior Vena Cava (SVC) & Inferior Vena Cava (IVC) $\rightarrow$ Right Atrium (RA) $\rightarrow$ Tricuspid Valve (TV) $\rightarrow$ Right Ventricle (RV) $\rightarrow$ Pulmonic Valve (PV) $\rightarrow$ Pulmonary Artery $\rightarrow$ Lungs (gas exchange) $\rightarrow$ Pulmonary Veins $\rightarrow$ Left Atrium (LA) $\rightarrow$ Mitral Valve (MV) $\rightarrow$ Left Ventricle (LV) $\rightarrow$ Aortic Valve (AV) $\rightarrow$ Aorta $\rightarrow$ Systemic Body Circulation.

Cardiac Conduction and Electrical Activity

• Conduction Pathway Components

  • Sinoatrial (SA) Node: Located in the upper wall of the right atrium; serves as the primary intrinsic pacemaker of the heart and establishes the regular sinus rhythm.

  • Atrioventricular (AV) Node: Situated in the floor of the right atrium near the interatrial septum; delays impulse transmission briefly to allow complete atrial emptying before ventricular contraction.

  • AV Bundle (Bundle of His): Receives impulses from the AV node and bifurcates into the right and left bundle branches traveling down the interventricular septum.

  • Purkinje Fibers: Terminal subendocardial conduction fibers that distribute impulses rapidly throughout the ventricular myocardium to trigger coordinated ventricular contraction.

• Electrocardiogram (ECG / EKG) Waveforms

  • P Wave: Represents atrial depolarization (electrical activation leading to atrial contraction).

  • QRS Complex: Represents ventricular depolarization (electrical activation leading to ventricular contraction); atrial repolarization occurs simultaneously but is masked by the QRS complex.

  • T Wave: Represents ventricular repolarization (electrical recovery and relaxation of the ventricles).

Mechanisms of Cardiac Control and Function

• Autonomic and Neural Control

  • Cardiac Control Center: Located within the medulla oblongata; integrates sensory inputs to regulate heart rate and stroke volume.

  • Baroreceptors: Specialized stretch receptors located in the aortic arch and internal carotid arteries that monitor systemic blood pressure changes.

  • Sympathetic Nervous System (SNS) Activation: Mediated via the cardiac accelerator nerve; increases heart rate (tachycardia) and enhances myocardial contractility.

  • Parasympathetic Nervous System (PNS) Activation: Mediated via Cranial Nerve X (CN X; vagus nerve); decreases heart rate (bradycardia).

• Physiological Factors Increasing Heart Rate

  • Elevated circulating levels of thyroid hormones or epinephrine.

  • Increased body temperature or infection (e.g., fever).

  • High environmental ambient temperature, particularly in high humidity conditions.

  • Physical exertion or exercise.

  • Tobacco smoking.

  • Systemic stress response.

  • Pregnancy.

• Coronary Circulation

  • Origin: Right and Left Coronary Arteries branch directly off the ascending aorta immediately distal to the aortic valve as part of the systemic circulation.

  • Left Coronary Artery (LCA) Branches:

  • Left Anterior Descending (LAD) / Interventricular Artery: Supplies the anterior ventricular septum and anterior wall of the left ventricle.

  • Left Circumflex Artery: Traverses the coronary sulcus to supply the left atrium and lateral/posterior left ventricle.

  • Right Coronary Artery (RCA) Branches:

  • Right Marginal Artery: Supplies the lateral wall of the right ventricle.

  • Posterior Interventricular Artery: Traverses the posterior interventricular sulcus to supply the posterior ventricular myocardium.

  • Functional Consideration: Numerous micro-branches extend to feed the myocardium and endocardium, but collateral circulation throughout these pathways is extremely limited.

• Phases of the Cardiac Cycle

  1. Diastole (Phase 1): Atria fill with venous return; all cardiac valves remain closed.

  2. Diastole (Phase 2): Increased pressure within the filling atria forces open the AV valves (tricuspid and mitral), allowing blood to flow passively into the ventricles.

  3. Systole Begins (Phase 3): Atria contract to empty remaining blood into ventricles ("atrial kick"); ventricles become fully distended.

  4. Systole (Phase 4): Ventricles begin active contraction; rapidly rising intraventricular pressure forces AV valves closed (preventing regurgitation); atria relax.

  5. Systole (Phase 5): High intraventricular pressure exceeds arterial pressures, forcing open the aortic and pulmonary semilunar valves; blood is forcefully ejected into the aorta and pulmonary artery.

  6. Diastole (Phase 6): Ventricles empty and relax; intraventricular pressure drops, causing aortic and pulmonary valves to snap closed to prevent arterial backflow.

• Parameters of Cardiac Function

  • Cardiac Output (CO): Total volume of blood ejected by a single ventricle in 1 minute.     $\text{CO} = \text{Stroke Volume (SV)} \times \text{Heart Rate (HR)}$     $\text{Average CO} = 70\,\text{mL} \times 70\,\text{beats/min} = 4900\text{--}5000\,\text{mL/min}$

  • Stroke Volume (SV): Volume of blood pumped out of a ventricle with each individual contraction (average baseline is $70\,\text{mL}$).

  • Heart Rate (HR): Total number of ventricular contractions per minute (average baseline is $70\,\text{beats/min}$).

  • Preload: The end-diastolic volume; the extent of myocardial stretch created by the volume of blood delivered to the ventricles by venous return prior to contraction.

  • Increased in hypervolemia, regurgitation of cardiac valves, and heart failure.

  • Afterload: The peripheral arterial resistance that the left ventricle must overcome to force open the aortic valve and eject blood into the systemic circulation.

  • Increased in systemic hypertension and arterial vasoconstriction.

  • Elevated afterload directly increases total cardiac workload: $\uparrow \text{Afterload} = \uparrow \text{Cardiac Workload}$.

• Blood Pressure Dynamics and Regulation

  • Systolic Pressure: The higher blood pressure reading; reflects peak pressure exerted against arterial walls during ventricular ejection.

  • Diastolic Pressure: The lower blood pressure reading; reflects resting pressure maintained in the arterial system during ventricular relaxation.

  • Arterial Blood Pressure Formula:     $\text{BP} = \text{Cardiac Output (CO)} \times \text{Peripheral Resistance (PR)}$

  • Factors Influencing Blood Pressure: Blood viscosity, venous return, rate and force of heart contractions, and elasticity of systemic arteries.

  • Vasodilation vs. Vasoconstriction:

  • Vasodilation: Increases vessel lumen size, reduces PR, and decreases blood pressure.

  • Vasoconstriction: Decreases vessel lumen size, increases PR, and increases blood pressure.

  • Endocrine and Neural Controls of BP:

  • Sympathetic Nervous System (SNS): Epinephrine release increases heart rate and contraction force, increasing CO and BP.

  • Hormonal Mechanisms: Antidiuretic Hormone (ADH), Aldosterone, and the Renin-Angiotensin-Aldosterone System (RAAS) drive systemic vasoconstriction and fluid retention to raise BP.

Diagnostic Tests for Cardiovascular Function

• Non-Invasive Diagnostic Tests

  • Electrocardiography (ECG / EKG): Evaluates electrical conduction; vital for detecting dysrhythmias, myocardial infarction, localized tissue infection, and pericarditis.

  • Auscultation: Direct listening to internal heart sounds via a stethoscope to detect structural valvular abnormalities, regurgitation, or abnormal blood shunts causing murmurs.

  • Echocardiography: Ultrasound recording that visualizes real-time valve movements, intra-cardiac blood flow patterns, chamber dimensions, and functional cardiac output.

  • Exercise Stress Tests: Treadmill or bicycle testing used to evaluate functional cardiovascular performance and ischemic responses under physiological workload.

  • Chest X-Ray Films: Radiographic imaging showing overall heart shape, gross size enlargement, and pulmonary vessel congestion.

  • Doppler Ultrasound Studies: Non-invasive assessment of blood flow velocity and direction in peripheral blood vessels, recording diagnostic sounds of arterial flow or venous obstruction.

• Invasive and Advanced Imaging Protocols

  • Nuclear Imaging: Tomographic radioactive tracer studies assessing myocardial perfusion, viability, and cellular damage.

  • Cardiac Catheterization: Direct insertion of a catheter into heart chambers to measure intravascular pressures, evaluate valve competence, assess overall cardiac pump function, and calculate central venous pressure (CVP) and pulmonary capillary wedge pressure (PCWP).

  • Angiography: Fluoroscopic visualization of coronary artery lumens following radiopaque contrast dye injection to localize vascular stenoses or occlusions.

• Laboratory Blood Analysis

  • Serum Lipid Profile: Quantifies serum levels of triglycerides and cholesterol fractions.

  • Electrolyte Panel: Measures serum concentration of critical electrolytes including sodium ($Na^+$), potassium ($K^+$), and calcium ($Ca^{2+}$).

  • Arterial Blood Gas (ABG) Determination: Direct measurement of arterial oxygenation ($pO_2$), carbon dioxide content, and systemic acid-base balance.

Coronary Artery Disease and Ischemic Heart Disorders

• Coronary Artery Disease (CAD) Overview

  • Terminology: Also designated as coronary heart disease, ischemic heart disease, or acute coronary syndrome.

  • Spectrum: Encompasses conditions ranging from transient angina pectoris to irreversible myocardial infarction (MI); can progress to chronic heart failure, lethal dysrhythmias, and sudden cardiac death.

  • Epidemiology: The leading overall cause of mortality in both men and women in the United States. Men tend to manifest disease earlier in life, whereas women present with higher rates of post-event complications.

  • Interventions: Diagnostic coronary angiograms; surgical revascularization via Coronary Artery Bypass Grafting (CABG) utilizing single, double, triple, or quadruple bypass grafts.

• Angina Pectoris: Clinical Features and Classification

  • Definition: Recurrent, intermittent, brief episodes of ischemic chest pain triggered by transient deficits in myocardial oxygen supply relative to metabolic demand due to narrowed coronary arteries.

  • Pain Characteristics: Substernal chest pressure, tightness, or crushing sensation that frequently radiates to the neck, jaw, back, or left arm.

  • Associated Symptoms: Profuse diaphoresis, nausea, and cutaneous pallor.

  • Clinical Types:

  • Classic / Exertional Angina: Predictable pain induced by physical exertion or stress, relieved by rest.

  • Variant / Prinzmetal / Vasospastic Angina: Caused by localized coronary artery spasms occurring unpredictably, often at rest.

  • Unstable Angina: Prolonged, severe, unprovoked pain occurring at rest; represents an unpredictable worsening of ischemia and serves as a direct precursor to acute myocardial infarction.

• Emergency Management Protocol for Angina

  1. Stop all physical activity immediately and place the patient in a resting state.

  2. Position the patient seated upright to reduce venous return and lower cardiac workload.

  3. Administer sublingual nitroglycerin (Nitro).

  4. Monitor vital signs, explicitly checking pulse rate and respiratory effort.

  5. Supplemental oxygen ($O_2$) should be administered if dyspnea or hypoxia is present.

  6. For patients with a known history of angina: Administer a second dose of sublingual nitroglycerin if chest pain persists after 5 minutes.

  7. For patients without a prior history of angina: Call emergency medical services immediately.

• Myocardial Infarction (MI)

  • Etiology: Complete occlusion of a coronary artery leading to localized myocardial ischemia, persistent cell hypoxia, tissue necrosis, and irreversible infarction.

  • Primary Causes: Atherosclerosis with thrombus formation (most common), or acute vasospasm.

  • Determinants: The size and anatomical site of coronary occlusion dictate the precise extent of tissue damage.

  • Warning Signs and Symptoms:

  • Sensation of intense pressure, heaviness, or burning in the chest, particularly during activity.

  • Sudden onset of shortness of breath, profound weakness, and exhaustion.

  • Nausea, indigestion, and epigastric discomfort.

  • Severe anxiety, apprehension, and fear of impending doom.

  • Pain pattern: Severe, crushing substernal pain radiating to the jaw, neck, shoulder, or left arm.

  • Diagnostic Findings:

  • ECG / EKG: ST-segment elevation (STEMI) relative to baseline, T-wave changes, and pathological Q waves.

  • Serum Biomarkers: Marked elevations in Troponin-I (highly specific) and Creatine Kinase-MB (CK-MB / CPK-MB). Secondary elevations seen in AST and LDH-1 over 24, 48, and 72 hours post-infarction.

  • Complete Blood Count (CBC): Leukocytosis (elevated white blood cell count).

  • Inflammatory Markers: Elevated C-reactive protein (CRP) and elevated Erythrocyte Sedimentation Rate (ESR).

  • Arterial Blood Gases (ABGs): Hypoxemia (decreased $pO_2$) and altered acid-base balance.

  • Major Complications:

  • Sudden death from lethal dysrhythmias (e.g., ventricular fibrillation).

  • Cardiogenic shock secondary to severe left ventricular contractile failure.

  • Congestive heart failure.

  • Myocardial wall rupture of necrotic tissue leading to cardiac tamponade.

  • Left ventricular mural thrombus formation leading to thromboembolism and Cerebrovascular Accident (CVA / stroke).

Cardiac Dysrhythmias and Cardiac Arrest

• Cardiac Dysrhythmias (Arrhythmias)

  • Definition: Deviations from normal cardiac rate or rhythm resulting from abnormalities in impulse initiation or electrical conduction.

  • Etiologies: Electrolyte imbalances (particularly $K^+$ and $Ca^{2+}$), high fever, tissue hypoxia, intense emotional stress, systemic infection, and drug toxicities.

  • Pathophysiological Impact: Impairs the mechanical efficiency of the heart's pumping cycle, decreasing net stroke volume and cardiac output.

• Sinus Node Abnormalities

  • Sinus Bradycardia: Regular sinus rhythm with a slow rate (typically <60\,\text{beats/min}).

  • Sinus Tachycardia: Regular sinus rhythm with a rapid rate (typically >100\,\text{beats/min}).

  • Sick Sinus Syndrome: Sinus node dysfunction characterized by alternating periods of marked bradycardia and tachycardia; frequently necessitates insertion of a permanent mechanical pacemaker.

• Cardiac Arrest

  • Definition: Total cessation of all cardiac electrical and mechanical activity; results in complete absence of cardiac output and presents as an Isoelectric/Flatline ECG (asystole).

  • Triggers: Excessive vagal nerve stimulation, severe potassium ($K^+$) imbalance, cardiogenic shock, drug toxicity, severe hypoxemia/insufficient oxygenation, acute respiratory arrest, or massive traumatic blow to the chest.

Congestive Heart Failure (CHF)

• General Concept

  • Occurrence where the heart is structurally or functionally unable to pump an adequate volume of blood to satisfy the metabolic demands of peripheral tissues.

  • Usually develops as a secondary complication to existing cardiopulmonary conditions (such as chronic hypertension or myocardial infarction).

  • Physiological compensatory mechanisms (activation of SNS, RAAS, myocardial hypertrophy) initially maintain CO but eventually increase cardiac workload and accelerate heart failure.

• Left-Sided Heart Failure Mechanics

  1. Left ventricle weakens and loses the capacity to empty efficiently.

  2. Decreased systemic cardiac output reduces tissue perfusion.

  3. Decreased renal arterial perfusion stimulates the juxtaglomerular apparatus to secrete renin, activating the RAAS and triggering aldosterone release, driving sodium and water retention.

  4. Inability to pump blood forward causes blood to back up into the pulmonary veins.

  5. Hydrostatic pressure increases within pulmonary capillaries, forcing fluid into alveolar spaces and producing pulmonary congestion or acute pulmonary edema.

• Right-Sided Heart Failure (Cor Pulmonale) Mechanics

  1. Right ventricle weakens and cannot empty blood into the pulmonary circuit.

  2. Decreased cardiac output forward flow to the lungs and systemic body.

  3. Decreased renal arterial blood flow stimulates renin, angiotensin, and aldosterone secretion, compounding systemic fluid retention.

  4. Blood backs up behind the right heart into the systemic venous circulation (superior and inferior venae cavae).

  5. High systemic venous hydrostatic pressure forces fluid into peripheral tissues, causing dependent edema in the legs, sacrum, liver, and abdominal organs.

  6. Severe venous pressure buildup causes jugular vein distension (JVD), hepatomegaly, splenomegaly, ascites, and cerebral edema.

• Comparative Summary of Clinical Features

  • Left-Sided Heart Failure Manifestations:

  • Shortness of breath (SOB), exertional dyspnea, orthopnea, and Paroxysmal Nocturnal Dyspnea (PND).

  • Pulmonary rales / crackles, wheezing, tachypnea, and cough producing blood-tinged sputum.

  • Reduced arterial oxygen pressure ($pO_2$), systemic cyanosis, restlessness, and confusion.

  • Elevated Pulmonary Capillary Wedge Pressure (PCWP).

  • Right-Sided Heart Failure Manifestations:

  • Jugular Vein Distension (JVD) and elevated peripheral venous pressure.

  • Dependent peripheral edema in lower extremities and sacral regions.

  • Ascites, abdominal distension, weight gain, anorexia, and GI distress.

  • Organomegaly (hepatomegaly and splenomegaly).

  • Forward Effects (Present in Both Left and Right HF):

  • Markedly decreased cardiac output (CO).

  • Compensatory tachycardia and peripheral vasoconstriction leading to cutaneous pallor.

  • Profound muscle fatigue and systemic weakness.

  • Impaired renal perfusion leading to oliguria and secondary polycythemia.

Valvular, Inflammatory, and Pericardial Disorders

• Valvular Defects

  • Primary sites of pathology are the AV valves (mitral and tricuspid) and semilunar valves (aortic and pulmonic).

  • Valvular Stenosis: Structural narrowing of the valve orifice, restricting forward blood flow and increasing the pressure workload of the chamber behind the valve.

  • Valvular Incompetence (Regurgitation): Failure of valve cusps to close completely, allowing blood to leak backward into the preceding chamber during contraction.

  • Mitral Valve Prolapse (MVP): Pathological condition characterized by abnormally enlarged, floppy mitral valve leaflets that balloon backward (prolapse) into the left atrium during ventricular systole.

  • Surgical Management: Valvular repair or surgical replacement utilizing mechanical artificial valves or biological tissue valves (derived from porcine, bovine, or equine tissue).

• Infective Endocarditis

  • Infection of the endocardium and heart valves, primarily caused by bacterial colonization (e.g., Streptococcus or Staphylococcus species) leading to vegetative growth on leaflets.

  • Clinical Manifestations: Recurrent low-grade fever, malaise, fatigue, anorexia, splenomegaly, and rapid onset of severe heart failure in severe cases.

  • Pathognomonic Cutaneous Signs:

  • Osler's Nodes: Tender, painful subcutaneous nodular lesions located on the digits.

  • Janeway Lesions: Non-tender, flat, erythematous, hemorrhagic, or pustular lesions situated on the palms or soles.

  • Diagnostic and Therapeutic Protocol: Repeated blood cultures to isolate the specific microbial agent; targeted intravenous (IV) antimicrobial therapy administered over several consecutive weeks.

• Pericarditis and Pericardial Effusion

  • Pathophysiology: Inflammation of the pericardium, typically secondary to open heart surgery, acute MI, rheumatic fever (RF), systemic lupus erythematosus, metastatic cancer, end-stage renal failure, chest trauma, or viral infection.

  • Acute Pericarditis: Simple pericardial inflammation where thickened, roughened pericardial layers rub directly against each other and the myocardium, producing a friction rub and severe chest pain.

  • Pericardial Effusion Mechanics:

  1. Inflammatory exudate or fluid accumulates in the pericardial sac.

  2. Fluid accumulation compresses the muscular heart wall (cardiac tamponade).

  3. Ventricles are mechanically restricted and cannot expand or fill adequately during diastole.

  4. Blood flow into the lungs drops dramatically.

  5. Systemic cardiac output drops severely.

  6. Venous return backs up directly into the systemic circulation.

  • Clinical Triad / Diagnostic Signs: Distended neck veins (JVD), muffled/faint heart sounds, and pulsus paradoxus (an exaggerated drop in systemic systolic blood pressure during inspiration).

Vascular Disorders: Essential and Secondary Hypertension

• Classifications of Hypertension

  • Clinical disorder characterized by elevated arterial blood pressure; affects any age group and demonstrates higher prevalence and severity in individuals of African descent.

  • Primary (Essential) Hypertension:

  • Idiopathic etiology (no identifiable single cause); accounts for the vast majority (>90\%) of all clinical cases.

  • Defined as sustained blood pressure consistently exceeding $140/90\,\text{mmHg}$ over prolonged periods.

  • Causes progressive microvascular and macrovascular damage to arterial walls.

  • Secondary Hypertension:

  • Arterial blood pressure elevation caused directly by an underlying identifiable disease process.

  • Common underlying pathologies: Renal parenchymal disease, renovascular stenosis, endocrine disorders, or pheochromocytoma (a benign catecholamine-secreting tumor of the adrenal medulla).

  • Management requires diagnostic identification and medical/surgical correction of the primary underlying cause.

• Pathophysiological Cascade and Target Organ Damage

  • Systemic arteriolar vasoconstriction $\rightarrow$ Increased total peripheral resistance (PR) $\rightarrow$ Sustained arterial blood pressure elevation.

  • Decreased renal blood flow $\rightarrow$ Increased juxtaglomerular renin secretion $\rightarrow$ Increased aldosterone production $ ightarrow$ Sodium and water retention $ ightarrow$ Expanded plasma volume $ ightarrow$ Progressive BP elevation.

  • High pressure increases cardiac workload $ ightarrow$ Left ventricular hypertrophy $ ightarrow$ Left-sided congestive heart failure.

  • Target Organ Complications:

  • Brain: Formation of cerebral microaneurysms; high rupture risk causing hemorrhagic Cerebrovascular Accidents (CVA / stroke).

  • Eyes: Hypertensive retinopathy, including arteriolar narrowing, microaneurysms, hemorrhages, and blindness.

  • Arterial System: Accelerated endothelial injury leading to severe systemic atherosclerosis.

  • Heart: Myocardial ischemia, angina pectoris, myocardial infarction, and left-sided heart failure.

  • Kidneys: Progressive nephrosclerosis, diabetic nephropathy aggravation, and chronic renal failure.

• Predisposing Risk Factors

  • Non-Modifiable Risk Factors:

  • Advanced age.

  • Biological sex: Higher frequency and severity in men compared to premenopausal women; female incidence increases significantly post-middle age.

  • Genetic predisposition and family history.

  • Race/Ethnicity (higher prevalence in individuals of African descent).

  • Modifiable Risk Factors:

  • High dietary sodium intake.

  • Excessive alcohol consumption.

  • Obesity and physical inactivity.

  • Cigarette smoking.

  • Exposure to prolonged or recurrent psychosocial stress.

• Clinical Manifestations

  • Frequently asymptomatic during early stages, earning the clinical designation of the "silent killer".

  • Early symptoms are vague, ambiguous, and non-specific:

  • Generalized systemic fatigue.

  • Persistent malaise.

  • Morning occipital headaches.