BMS200 - week 9

Primary Hypertension

• More than 90% of patients with primary hypertension have no single clear abnormality.
• Major factors include:
  • Arteriolar vasoconstriction and altered endothelial function
  • Increased sodium retention and increased renin secretion
  • Increased activation of the sympathetic nervous system
• Common factors are interconnected and contribute to the condition.

Secondary Hypertension

• Secondary hypertension is caused by identifiable medical conditions.
• Possible causes include:
  • Renal disease
  • Obstructive sleep apnea
  • Endocrine disorders
  • Congenital conditions
  • Medications and substances

Importance of Arteriolar Tone in Hypertension

• High blood pressure increases the responsiveness of resistance vessel walls to vasoactive stimuli.
• Even in maximally dilated vessels, resistance is increased due to decreased lumen size in hypertension.
• Increased vessel wall thickness due to smooth muscle contraction raises resistance, inversely proportional to the fourth power of the lumen radius.
• Resistant vessels are a key area for blood pressure control.

Vascular Factors in Primary Hypertension

• Arterioles in hypertensive patients have increased tone compared to non-hypertensive individuals.
• Over time, arteriole walls undergo remodelling:
  • Smooth muscle cell hypertrophy and hyperplasia.
  • Increased extracellular matrix deposition.
  • This process is known as arteriolosclerosis.
• The vascular endothelium of hypertensive patients releases fewer vasodilatory substances like nitric oxide (NO).
• Larger vessels can also be remodelled and become stiffer. The exact pathological contributions of large vessel arteriosclerosis to hypertension are not fully understood.

Diagnosis of Hypertension - Canadian Guidelines

• Multiple visits are usually required for a diagnosis unless the hypertension is severe (>180/110 mmHg).
• Home blood pressure measurements are superior to office readings, as they are less prone to "white coat hypertension."
• Automated blood pressure measurements are preferable to those taken by a healthcare professional.
• 24-hour blood pressure measurements are highly beneficial, especially when high blood pressure persists during sleep.
• If the average awake systolic blood pressure is 135 mmHg or diastolic blood pressure is 85 mmHg using automated measurements, hypertension is diagnosed.
• For 24-hour measurements, the average should be less than 130/80 mmHg.
• In individuals with diabetes, hypertension is diagnosed at a blood pressure of ≥ 130/80 mmHg.
• If office measurements are used, a diagnosis requires 4-5 visits with an average systolic blood pressure of 140 mmHg or diastolic blood pressure of 90 mmHg.

Hypertensive Urgencies and Emergencies

• Hypertensive urgency refers to significantly elevated blood pressure that requires urgent treatment to reduce the risk of organ damage.

Vasculitis

• Vasculitis is inflammation of blood vessels, which can lead to damage and damage and dysfunction of organs depending on the location of the inflammation.
• Causes include:
  • Immune system disorders (like rheumatoid arthritis or lupus)
  • Infections (such as hepatitis B)
  • Genetic factors

Types of Vasculitis

• Two main types of vasculitis are:
  • Giant cell arteritis: Inflammation of large arteries, often affecting the temporal artery.
    • Characterized by granulomas often formed by Th1/Th17 helper T-cell responses.
  • Polyarteritis nodosa: Inflammation of small and medium-sized muscular arteries.
    • Often associated with hepatitis B infection.
    • May involve multiple organs, including the kidneys, heart, and nervous system.
    • Involves immune complex formation (Type III hypersensitivity).

Polyarteritis Nodosa

• Can cause thrombosis causing an infarct or aneurysms that rupture and bleed, leading to either death or severe dysfunction depending on the site of the bleeding or infarct.

Granulomatosis with Polyangiitis (GPA)

• Necrotizing vasculitis involving small arteries and veins, characterized by intravascular or extravascular granuloma formation.
• Common sites of involvement include the upper respiratory tract, lower respiratory tract, and kidneys.
• Renal involvement is associated with significant morbidity and mortality.

Raynaud's Phenomenon

• Intermittent bilateral but patchy/asymmetric ischemia of the fingers and toes due to transient vasospasm.
• May be precipitated by cold or stress.
• Rarely progresses to ulceration or gangrene.
• Can occur in isolation (Raynaud's disease/disorder) or accompany immune disorders such as lupus or systemic sclerosis.

Anti-Neutrophil Cytoplasmic Antibodies (ANCAs)

• Antibodies against neutrophil proteins found in the cytoplasm.
  • p-ANCA: Found near the neutrophil nucleus, and binds to myeloperoxidase.
  • c-ANCA: Found throughout the cytoplasm and binds to proteinase-3.
• Thought to contribute to neutrophil activation and increased neutrophil release of cytokines, leading to leukocyte recruitment and endothelial cell damage.

Management of Vasculitis

• Treatment depends on the specific type of vasculitis, but generally involves:
  • Corticosteroids
  • Immunosuppressive medications
  • Biologic therapies
• Prompt diagnosis and treatment are crucial to minimize complications.

ECGs and their role in cardiac physiology

• ECGs measure the extracellular electrical activity of the heart and capture the changes in membrane potential of cardiac cells.
• ECGs detect the electrical current flowing from depolarized cells to resting (polarized) cells.
• ECGs only "notice" changes in membrane potential, not plateaus in the cardiac action potential (like phases 4 and 2).
• The amplitude of the ECG waves represents the magnitude of the electrical potential difference across parts of the heart.
• The vector of depolarization, indicating the direction of the electrical impulse, is represented relative to the ECG lead placement.

ECG Lead Placement

• ECG leads are placed to provide a three-dimensional view of the electrical activity of the heart.
• Coronal view is achieved through leads placed on the left and right arms and the left leg.
• Cross-sectional view is achieved through precordial leads.
• Bipolar leads measure voltage changes between two leads, for example, lead I compares changes between the right arm and the left arm.
• "Unipolar" (precordial) leads compare voltage changes between a lead (chest wall surface) and the center of the heart.

ECG Time and Voltage Axis

• The x-axis of an ECG represents time (in seconds).
• The y-axis of an ECG represents electrical potential changes (voltage in mV), with a small box representing 0.1 mV and 0.04 seconds, and a big box representing 0.5 mV and 0.2 seconds.

Step-by-step approach to ECG interpretation

• It is crucial to analyze ECG waves in all leads as they can change from lead to lead.
• An ECG should be analyzed systematically, starting with the rhythm, then the P waves, the PR interval, the QRS complex, and the ST segment, and finally analysing the T waves.
• If ST segment depression or elevation is observed, it is crucial to consider the underlying cause and rule out an infarct.

Abnormal Q-waves

• Significant Q-waves are wide (>0.04 sec), large (>2 mm deep or >25% of the QRS), or >1/3 the height of the R wave.
• Abnormal Q-waves in leads V1-V3 are always concerning and may indicate a previous or ongoing myocardial infarction (MI).

Abnormal ST Segment

• ST segment changes are usually evaluated in terms of elevation or depression rather than intervals.
• ST segment depression or elevation can indicate various conditions besides MI.

Abnormal T-waves

• T-wave abnormalities should be assessed in relation to age and the specific lead pattern.
• Tall T-waves can indicate hyperkalemia, early MI, myocardial infarction, and ventricular hypertrophy.
• Small T-waves can indicate hypokalemia.
• Inverted T-waves can signal myocardial infarction, ventricular hypertrophy, ischemic changes, metabolic strain, and electrolyte abnormalities.

Arrhythmias

Atrial Fibrillation

• It is characterized by a narrow complex "irregular irregular" pattern with no distinguishable P waves.
• It is the leading cardiac cause of stroke.

SVT

• It can be either regular or irregular.
• It originates in the atria or AV node.
• The ECG shows a fast heart rate (150-250 bpm) with often narrow QRS.

PVCs

• They can occur in isolation, pairs, or triplets.
• It is common, occurring in 1-4% of the population.
• The ECG shows abnormal and wide QRS complex occurring earlier than expected during the cardiac cycle.

Ventricular Fibrillation

• It is life-threatening and characterized by no identifiable P wave, QRS complex, or T wave on the ECG.
• It is a fast unstable rhythm with a heart rate between 150-500 bpm.
• The ECG shows irregular and varying amplitudes and shapes.

Torsades de Pointes

• It is a polymorphic form of ventricular tachycardia.
• The ECG shows QRS complexes of varying amplitude and "twisting" pattern.
• It is associated with QT prolongation (>500 ms) due to congenital or acquired factors.
• It can progress to ventricular fibrillation.

Idioventricular Rhythm

• The ECG shows a slow and regular rhythm, absence of P waves, and a prolonged QRS interval, with a rate less than 50 bpm.
• The ventricles are acting as a pacemaker due to SA node malfunction.

Heart Blocks

First-Degree AV Block

• It is characterized by a prolonged PR interval (>200 ms) on the ECG.
• It is often asymptomatic.

Second-Degree AV Block

• It is characterized by a delayed conduction in the AV node resulting in prolonged PR intervals and dropped QRS complexes.
• Mobitz Type 1 (Wenckebach) is characterized by progressive prolongation of the PR interval until a QRS complex is dropped.
• Mobitz Type 2 is characterized by consistent PR intervals with sudden drops of missed QRS complexes.

Third-Degree AV Block (Complete Heart Block)

• It is characterized by complete absence of conduction from the atria to the ventricles, leading to independent atrial and ventricular rates.
• It can cause severe bradycardia, syncope, or heart failure.

1st-Degree Heart Block

• It involves a prolonged PR interval (>0.2 seconds) caused by slowed conduction through the AV node.
• It is often asymptomatic.
• It may indicate increased vagal tone (younger patients) or fibrotic changes (elderly patients).

Mobitz Type 1 (Wenckebach) Heart Block

• It is characterized by progressive prolongation of the PR interval until a QRS complex is dropped.
• It is often asymptomatic.
• It can be due to increased vagal tone.
• It may indicate structural heart disease, especially in older patients.

Mobitz Type 2 Heart Block

• It is characterized by consistent PR intervals with one dropped QRS complex at a time.
• It can progress to complete heart block.
• It is a serious condition that may require a pacemaker.

3rd-Degree Heart Block

• It is characterized by a complete block between the atria and ventricles.
• The ventricles are paced by the Purkinje fibers, leading to a slow heartbeat.
• It is a serious condition that requires immediate treatment including a pacemaker.

Sleep, Part 1 - Physiology of Sleep and Sleep Disorders

• Sleep constitutes about one-third of our lives.
• Sleep disruption increases the risk of stroke, hypertension, and coronary artery disease.
• Only about 30% of adults in North America report getting enough sleep, and 50% report that their sleep is disturbed.
• Sleep deprivation degrades cognitive performance, and deep sleep seems to be more critical for cognitive function.
• Polysomnography is used to measure the states of wakefulness to sleep.
• Electroencephalogram (EEG) surface electrodes are attached to the skull to measure brain activity.
• Electromyogram (EMG) electrodes are attached to skeletal muscle to measure muscle activity.
• Electrooculogram (EOG) electrodes measure eye movements.
• During REM sleep, descending connections from REM-on neurons activate spinal inhibitory neurons that use GABA as a neurotransmitter.
• This is why those in REM sleep are effectively paralyzed - very few movements, other than an occasional finger- or toe-twitch.
• The large delta waves seen during N3 sleep are due to oscillations in activity between the thalamus and the cortex.
• During REM sleep, electrical activity occurs in the cortical association areas and is not synchronized.

Sleep Architecture

• Sleep architecture refers to how a person progresses through each stage of sleep at night.
• It includes duration spent in each stage, frequency and timing of each stage, and the frequency of awakenings.
• Sleep architecture changes throughout the lifespan.
• The first sleep period is the longest, and the rest tend to last 90–110 minutes.
• Healthy young adults and children usually get the most deep sleep (N3) early, soon after falling asleep.
• We usually progress through the stages in an orderly sequence, though sometimes the transition through N1 and N2 sleep is very quick.
• We never go from wakefulness directly to REM sleep.
• We arrive at REM sleep after ascending through deeper levels of sleep, usually N3 but sometimes N2.
• Most REM sleep occurs near the end of a sleep session.
• Elderly subjects have fewer and shorter periods of N3 sleep, and more frequent awakenings.
• Young children spend a lot of time in N3 and REM.
• Almost 50% each in neonates and steadily declines with age until ~25% each in young adults.

Sleep Stages

• Stage I (N1): Theta rhythm, 4 - 7 Hz, rolling eye movements, some muscle activity, easily wakened, may seem somewhat awake but no short-term memory.
• Stage II (N2): Theta with K complexes + sleep spindles, limited eye movement, some MSK movement, sleep is still light but more difficult to awaken than N1.
• Stage III (N3): Appearance of delta waves, 0.5 – 4 Hz, limited eye movement, some MSK movement, subject is very difficult to awaken and will be disoriented, sometimes dreams reported, more N3 early in the sleep session, less later.
• Stage IV (N3): Bigger, Slower delta waves.
• REM (R): Dys-synchronized theta-like, bursts of eye movements, almost no MSK movement, subject is easy to awaken, and often will report dream content. More REM late in the sleep session, less early on. Need to be in N2 or N3 prior to entering REM.

Neurophysiology of Sleep

• In general, the arousal system keeps us awake and opens the gate of the thalamus.
• The arousal system communicates widely to hypothalamic areas that regulate sleep cycles, and to the cortex in general.
• Major components of the arousal system include brainstem nuclei that extend mostly through the midbrain and pons.
• Locus ceruleus: norepinephrine
• Raphe nucleus: serotonin
• Tuberomamillary body: histamine
• Acetylcholine: has multiple nuclei in the brainstem that are important in arousal.
• Periaqueductal gray: dopamine
• The ventrolateral pre-optic nucleus (VLPO) is one of the major sleep-promoting nuclei, and releases inhibitory neurotransmitters like GABA and galanin.
• REM sleep is likely regulated differently – in the brainstem there are “REM-on” (lateral pontine areas) and “REM-off” groups (pons portion of the locus ceruleus).
• REM-on neurons inhibit the REM-off neurons, and REM-off neurons inhibit REM-on neurons.
• REM-on neurons project widely and are stimulated by cholinergic inputs.
• REM-off neurons tend to be stimulated by norepinephrine and serotonin inputs, and are also stimulated by orexin release from the lateral hypothalamus.

Melatonin and Circadian Rhythms

• Melatonin is produced in the pineal gland.
• Melatonin production is indirectly stimulated during periods of darkness.
• Melatonin is an interesting metabolite of serotonin that may have other functions other than the entrainment of circadian rhythms.
• In the absence of light, the retinohypothalamic fibers relay “dark info” to the SCN, lifting the inhibition of the PVN by the SCN.
• The PVN then activates the sympathetic nervous system:
  • Intermediolateral horn cells excite post-ganglionic neurons in the superior cervical ganglion.
  • NE is released at the pineal gland, leading to melatonin synthesis and release.
• Serotonin is synthesized in the pineal gland.
• Catecholamine stimulation (beta1-receptors) increases the activity and production of AANAT and the availability of serotonin, leading to more melatonin synthesized.
• With withdrawal of catecholamines, AANAT is degraded by proteosomes.

Narcolepsy

• Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness, cataplexy, sleep paralysis, hypnagogic hallucinations, and automatic behaviors.
• Narcolepsy with cataplexy (Type I narcolepsy) is usually autoimmune.
• HLA DQB1*06:02, an MHC II gene is found in >90% of people with narcolepsy with cataplexy.
• Possible molecular mimicry of orexin with common respiratory tract pathogenic, including viral influenza and streptococcal species.
• Treatment usually involves antidepressants or stimulants.

Restless Legs Syndrome (RLS) and Periodic Limb Movement Disorder (PLMD)

• RLS is characterized by an unpleasant, irritating compulsion to move the legs triggered by rest, drowsiness, or sleep.
• PLMD occurs during sleep, and involves movements, often large, that frequently involve the legs.
• Both are associated with iron deficiency and abnormalities in dopaminergic signaling.
• RLS likely involves excessive dopamine activity in the morning and inadequate dopamine activity at night.

Obstructive Sleep Apnea

• Obstructive sleep apnea is a sleep disorder characterized by repeated episodes of upper airway obstruction during sleep, leading to pauses in breathing.
• The pauses in breathing can cause loud snoring, gasping, and choking sounds.
• Obstructive sleep apnea can lead to daytime sleepiness, fatigue, and other health problems.

Explore the complexities of hypertension in this quiz focused on primary and secondary hypertension. Delve into the underlying causes, contributing factors, and the significance of arteriolar tone in managing high blood pressure. Test your knowledge on how these different forms of hypertension impact health.