Effect of Heart Rate on Duration of Cardiac Cycle

Cardiac Cycle

The cardiac events that occur from the beginning of one heartbeat to the beginning of the next are called the cardiac cycle. Each cycle is initiated by spontaneous generation of an action potential in the sinus node. This node is located in the superior lateral wall of the right atrium near the opening of the superior vena cava, and the action potential travels from here rapidly through both atria and then through the A-V bundle into the ventricles. Because of this special arrangement of the conducting system from the atria into the ventricles, there is a delay of more than 0.1 seconds during passage of the cardiac impulse from the atria into the ventricles. This allows the atria to contract ahead of ventricular contraction, thereby pumping blood into the ventricles before the strong ventricular contraction begins. Thus, the atria act as primer pumps for the ventricles, and the ventricles, in turn, provide the major source of power for moving blood through the body’s vascular system.

Shows the different events during the cardiac cycle for the left side of the heart. The top three curves show the pressure changes in the aorta, left ventricle, and left atrium, respectively. The fourth curve depicts the changes in left ventricular volume, the fifth the electrocardiogram, and the sixth a phonocardiogram, which is a recording of the sounds produced by the heart-mainly by the heart valves-as it pumps. It is especially important that the reader study in detail this figure and understand the causes of all the events shown.

When heart rate increases, the duration of each cardiac cycle decreases, including the contraction and relaxation phases. The duration of the action potential and the period of contraction (systole) also decrease, but not by as great a percentage as does the relaxation phase (diastole). At a normal heart rate of 72 beats/min, systole comprises about 0.4 of the entire cardiac cycle. At three times the normal heart rate, systole is about 0.65 of the entire cardiac cycle. This means that the heart beating at a very fast rate does not remain relaxed long enough to allow complete filling of the cardiac chambers before the next contraction.

Pharyngitis – Basic Information, Clinical Presentation, And Its Treatment

Basic Information

• Outpatient visits for pharyngitis account for 1% to 2% of all office visits.
• Most common cause is viral in adults, with a much higher incidence of group A streptococci in children.
• Some cases may be associated with evidence of more systemic infection (Epstein-Barr virus [EBV], acute HIV infection); severe pharyngitis (Neiserria gonorrohoeae or group A β-hemolytic streptococci [GABHS]); adult patients with a history of rheumatic fever managed differently, with lower threshold for prescription of antibiotics.
  1/ Viral infection causes most adult cases (~80%).
  2/ Rhinovirus (20%) is most common viral cause.
  3/ Coronavirus (5–10%), adenovirus (5%), herpes simplex (2– 4%) less common.
  4/ Uncommon causes include parainfluenza (2%), influenza (1%), EBV (<1%), cytomegalovirus (<1%), acute HIV type 1 (<1%), coxsackievirus (<1%).
• Bacterial infection less common in adults than children.
• Streptococcus pyogenes most common bacterial cause in adults (5–10%).
  1/ Other streptococci less common, usually group G or C.
  2/ Rare bacterial causes include N. gonorrhoeae (<1%), Corynebacterium diphtheriae (<1%), Arcanobacterium haemolyticum (often associated with rash <1%), Chlamydophila pneumoniae (1%), Mycoplasma pneumoniae (<1%).
• Many cases unknown and presumed viral.
  
  
  
  

Clinical Presentation

• Typical presentations include sore throat and malaise with possible fever or cervical lymphadenopathy.
• Severe sore throat with inability to swallow secretions or associated dyspnea should be evaluated in an emergency department setting; may indicate epiglottitis.
• Dehydration in severe cases may require IV hydration.
• Red, beefy tonsils with exudates may have either bacterial or viral causes (i.e., presence of exudate is not specific for bacterial cause.
• Primary infection with EBV (infectious mononucleosis) may present with fever, sore throat, and lymphadenopathy (anterior and posterior cervical lymph nodes—may be generalized and include splenomegaly) and is easily confused with GABHS.
  1/ In infectious mononucleosis, laboratory abnormalities may include predominance of lymphocytes or atypical lymphocytes. In 90% of adult cases, the aspartate aminotransferase, alanine aminotransferase, or lactate deyhydrogenase level is elevated to at least two to three times normal.
  2/ Prescription of amoxicillin for mistakenly believed or secondary concurrent GABHS predictably yields diffuse, pruritic, maculopapular rash in 95% to 100% of patients (rash does not mean patient is amoxicillin allergic for future dosing.

Diagnosis

Because the signs and symptoms of group A streptococcal and other viral presentations overlap, physicians are generally unable to include or exclude the diagnosis of streptococcal pharyngitis on epidemiologic and clinical grounds; therefore, laboratory testing should be done to determine whether group A streptococci are present in the pharynx.

• Throat culture gold standard (90% sensitive)
  • False positives may result from carrier state
• Rapid strep tests
  1/ Throat swab detecting carbohydrate antigen
  2/ Sensitivity 80% to 90% in adults but highly specific
  3/ If positive test, treat as GABHS; no further culture required
  4/ In children and adolescents, negative tests should be confirmed by standard culture. It is unclear whether this is necessary in adults.
• Sensitivity and specificity of clinical presentation 50% to 75% for GABHS.
• The production of heterophile antibodies used to diagnose infectious mononucleosis (that are not directed against EBV but agglutinate either horse or sheep red blood cells [RBCs]) occurs in 90% of cases and is detected by blood testing with commercial kits (e.g., Monospot, Meridian Bioscience, Cincinnati, OH).
  1/ Detection of anti-EBV capsid immunoglobulin M (IgM) antibodies typically done if heterophilic antibodies are negative but EBV still suspected (~10% of cases).
  2/ Anti-EBV immunoglobulin G (IgG) may be present at presentation in new infection or with preexisting infection and has less clinical utility in diagnosis of acute infection.
  
  
  
  

Treatment

• Viral: Generally benign, self-limited illness remedied by​​​ rest, hydration, nonsteroidal drugs for pain or fever, and saltwater gargles
• GABHS: Historically, treatment is given to avoid complications of acute rheumatic fever and may prevent suppurative complications such as tonsillar abscess. However, acute rheumatic fever is now rare in adults, and the main use of antibiotics offers shorter duration of illness (16–24 hours) if given within 72 hours of symptom onset.
  1/ All GABHS strains remain penicillin sensitive.
  2/ Penicillin (PCN) V standard for adults, 250 mg four times daily or 500 mg twice daily orally; long-acting intramuscular PCN given as one dose (1.2 million units benzathine ± procaine PCN G).
  3/ Erythromycin 250 mg four times daily or 500 mg twice daily orally for PCN-allergic patients.

Normal Structure and Function of the Kidney : Anatomy, Histology and Cell Biology

The kidneys maintain homeostasis while functioning under a tremendous range of environmental water and salt availability.

For example, the kidneys have the capacity to excrete free water in freshwater fish, varying amounts of water and solute in humans, and an extremely concentrated urine in the kangaroo rat, which can live its entire life without access to water. The kidneys are a pair of encapsulated organs located in the retroperitoneal area. A renal artery enters and a renal vein exits from each kidney at the hilum. Approximately 20% of cardiac output goes to the kidneys. Blood is filtered in the kidneys, removing wastes—in particular urea and nitrogen-containing compounds—and regulating extracellular electrolytes and intravascular volume. Because renal blood flow is from cortex to medulla and because the medulla has a relatively low blood flow for a high rate of metabolic activity, the normal oxygen tension in the medulla is lower than in other parts of the kidney. This makes the medulla particularly susceptible to ischemic injury.

The anatomic unit of kidney function is the nephron, a structure consisting of a tuft of capillaries termed the glomerulus, the site at which blood is filtered, and a renal tubule from which water and salts in the filtrate are reclaimed. Each human kidney has approximately 1 million nephrons.

A glomerulus consists of an afferent and an efferent arteriole and an intervening tuft of capillaries lined by endothelial cells and covered by epithelial cells that form a continuous layer with those of the Bowman capsule and the renal tubule. The space between capillaries in the glomerulus is called the mesangium. Material comprising a basement membrane is located between the capillary endothelial cells and the epithelial cells .

Closer examination of glomerular histology and cell biology reveals unique features not found in most peripheral capillaries. First, the glomerular capillary endothelium is fenestrated. However, because the endothelial cells have a coat of negatively charged glycoproteins and glycosaminoglycans, they normally exclude plasma proteins such as albumin. On the other side of the glomerular basement membrane are the epithelial cells. Termed “podocytes” because of their numerous extensions or foot processes, these cells are connected to one another by modified desmosomes.

The mesangium is an extension of the glomerular basement membrane but is less dense and contains two distinct cell types: intrinsic glomerular cells and tissue macrophages. Both cell types contribute to the development of immune-mediated glomerular disease by their production of, and response to, cytokines such as transforming growth factor-β (TGF-β).

Understanding the complex organization of the glomerulus is crucial for understanding both normal renal function and also the characteristics of different glomerular diseases. Thus, in some conditions immune complexes may accumulate under the epithelial cells, whereas in others they accumulate under the endothelial cells. Likewise, because immune cells are not able to cross the glomerular basement membrane, immune complex deposition under the epithelial cells is generally not accompanied by a cellular inflammatory reaction.

The renal tubule itself has a number of different structural regions: the proximal convoluted tubule, from which most of the electrolytes and water are reclaimed; the loop of Henle; and a distal convoluted tubule and collecting duct, where the urine is concentrated and additional electrolyte and water changes are made in response to hormonal control.

Headaches & Acute Treatment

Headache is one of the commonest neurological presentations to primary care and neurology clinics.

CLASSIFICATION

The International Headache Society (IHS) classification for headache (ICHD- 2) considers headache disorders to be either primary or secondary. Headaches can be broadly categorized into three groups:

_ Primary headache syndromes

• Migraine with and without aura
• Tension-Type Headache (TTH)
• Cluster headache and other TA Cs, e.g. paroxysmal hemicrania (PH), hemicrania continua (HC), and short- lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT)
• Other primary headaches, e.g. primary cough, exertional, stabbing and thunderclap headaches, and headache associated with sexual activity.
  
  
  
  
  
  

_ Secondary headache syndromes

• Headaches secondary to head and neck pathology
• Substance use or its withdrawal
• Psychiatric disorder

_ Cranial neuralgias and facial pain, e.g. trigeminal neuralgia

MIGRAINE

Migraine is a common headache disorder. In adults, it is typically unilateral but can be bilateral. It is moderate to severe in intensity, has an insidious onset over minutes to hours, and is described as pulsating or throbbing.

_ Acute treatment of episodic migraine

• First line: aspirin, oral triptan, NSAID, or paracetamol.
• Second line: Non-oral triptan or combination therapy.
• If treatment failure with the above, ergot alkaloids may be used.
• Drugs to avoid: opioids.
• Adjuncts: prokinetic agents, e.g. metoclopramide or domperidone, should be given if there is nausea/ vomiting or suspicion of significant absorption delay due to gastric stasis.

_ Mini- prophylaxis for menstruation- associated migraine

• First line: Short course frovatriptan or NSAID.
• Second line: naratriptan or zolmitriptan

_ Preventative treatment for episodic migraine

• First line: metoprolol, propranolol, topiramate, or sodium valproate.
• Propranolol may be preferred in women of childbearing age, due to the risk of teratogenicity with topiramate and valproate.
• Second line: acupuncture, amitriptyline, flunarizine, or pizotifen.
• Third line: if treatment failure with the above, suggest candesartan, duloxetine, gabapentin, magnesium, methysergide, or venlafaxine.
• Migraine prophylaxis is deemed successful when headache attacks fall by at least 50% in 3 months.

TENSION-TYPE HEADACHE

TTH is the commonest headache type, with a lifetime prevalence of 42% in men and 49% in women. TTH is typically bilateral and is described as a ‘tightening’ or ‘pressure’. It can be associated with muscle tenderness around the head and neck and with nocturnal bruxism.

_ Acute treatment of TTH

• First line: NSAIDs and/ or paracetamol.
• Second line: a combination of NSAIDs or paracetamol with caffeine.
• Drugs to avoid: opioids and triptans.
• Also consider: electromyography (EMG) biofeedback, cognitive
  behavioural therapy (CBT), and relaxation therapy.

_ Treatment of Chronic TTH

• First line: acupuncture or amitriptyline.
• Second line: mirtazapine or venlafaxine

TRIGEMINAL AUTONOMIC CEPHALALGIAS

TA Cs are a group of primary headache disorders that comprise unilateral trigeminal pain with autonomic features such as lacrimation and rhinorrhea.

CLUSTER HEADACHE

Cluster headache is characterized by severe unilateral attacks of orbital/supraorbital/ temporal pain, associated with restlessness and cranial autonomic features (ptosis, miosis, conjunctival injection, lacrimation, nasal congestion, rhinorrhea). The attacks are short- lived (lasting from 15min to 3h), and patients may experience up to eight attacks a day.

_ Acute treatment

• First line: high- flow oxygen (100% oxygen at 10– 15L/ min for 10– 20min with a non- rebreathe mask) and/ or nasal or SC triptan.
• Second line: intranasal lidocaine, SC octreotide, or oral zolmitriptan.
• Drugs to avoid: ergots, hyperbaric oxygen, and opioids

SECONDARY HEADACHE

IDIOPATHIC INTRACRANIAL HYPERTENSION

IIH typically occurs in women who are overweight and of childbearing age. It is also associated with excessive vitamin A intake, growth hormone therapy, and tetracycline antibiotics, and has been linked with certain systemic illnesses, including systemic lupus erythematosus (SLE), hypoparathyroidism, sleep apnoea, and polycystic ovary syndrome (PCOS).

_ MANAGEMENT

• First line: acetazolamide.
• Other drugs to consider: corticosteroids, loop diuretics, topiramate.
• Other management strategies: repeated lumbar puncture (LP), surgery including lumboperitoneal shunting and optic nerve sheath fenestration.

MEDICATION OVERUSE HEADACHE (MOH)

MOH occurs in patients with primary headache disorders who take acute analgesic medication regularly for >3 months. The culprit agents are:

• Ergots, opioids, and triptans for ≥10 days per month;
• Aspirin, NSAIDs, and paracetamol, alone or in combination for ≥15 days per month.

_ MANAGEMENT

_ If drug treatment is also required:

• First- line treatment: topiramate 100– 200mg/ day;
• Second- line treatment: amitriptyline (up to 50mg/ day), corticosteroids (up to 60mg/ day), or NSAIDs