multidrug-resistant-organisms

[multidrug-resistant-organisms]

RNA- Properties, Structure, Types and Functions

Ribonucleic acid (RNA) is a polymer of nucleotides, essential for various biological functions including coding, decoding, regulation, and expression of genes. 

Properties of RNA 

RNA Is a single-stranded helix 

The strand as a 5′ end with a phosphate group and a 3′ end with a hydroxyl group

It is composed of ribonucleotides 

The ribonucleotides are linked together by 3′  → 5′ phosphodiester bonds

The nitrogenous bases that compose the ribonucleotides include adenine, cytosine, uracil, and guanine 

The bases that DNA consists of include adenine, thymine, cytosine, and guanine

In RNA, uracil replaces thymine. Though these poth pair with adenine 

Most RNA molecules are single-stranded, however an RNA molecule may have regions that can form complementary base pairing where the RNA strand loops back on itself. If this so happens, the RNA will have double sided region(s)

rRNA and tRNA substantially exhibit this secondary structure, as do some mRNAs

Types of RNA 

In both prokaryotes and eukaryotes, there are 3 main types of RNA 

rRNA - ribosomal RNA

tRNA - transfer RNA

mRNA - messenger RNA 

mRNA - Messenger RNA 

mRNA carries the genetic code that is copied form the DNA during transcription in what we call codons. Codons are triplets of nucleotides. mRNA carries codons which are segments of genetic code derived from DNA during the process of transcription 

As mentioned before, mRNA contains a 5′ cap and a 3′ tail

The 5′ end is capped with a guanosine triphosphate nucleotide, which helps in mRNA recognition during translation and/or protein synthesis 

The 3′ end has a poly A tail, which prevents enzymatic degradation of mRNA

mRNA takes the genetic code from DNA and uses that to synthesize proteins

mRNA carries genetic information from the nucleus of a cell toits cytoplasm 

rRNA - Ribosomal RNA 

Different strands of rRNA present in the ribosomes in either small sized rRNA or large sized rRNA, which denote their presence in the small and large subunits of the ribosome

rRNA combines with proteins in the cytoplasm to form ribosomes, which act as the site of protein synthesis 

rRNA also contains enzymes needed for the process of protein synthesis 

During translation, rRNA travels along the mRNA molecule and facilitates the assembly of amino acids to form a polypeptide chain. rRNA is also able to bind to tRNA and other molecules that are crucial for protein synthesis 

tRNA - Transfer RNA 

The main function of tRNA is during translation; tRNA transfers amino acids during protein synthesis

Each of the 20 amino acids has a specific tRNA that binds with it and transfers it to the growing polypeptide chain formed during translation

tRNA also acts as an adapter in the translation of the genetic sequence involving mRNA translating into proteins 

tRNA has a clover leaf structure stabilized by strong hydrogen bonds between the nucleotides. The hydrogen bonds form 3 structural loops

The 3′ end serves as the amino acid attachment site

The center loop encompasses the anticodon. The anticodon is a 3-base nucleotide sequence that binds to the mRNA codon 

This interaction between codon and anticodon specifies the next amino acid to be added during protein synthesis 

Transfer RNA brings amino acids to the ribosome. Each amino acid corresponds to one of the codons on the rRNA. The amino acids can then be joined together to make polypeptides and proteins 

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[multidrug-resistant-organisms]

Eukaryotic Cells - The Nucleus

All eukaryotic cells have at least one nucleus (prokaryotic cells, such as bacteria, lack a nucleus and nuclear membrane). Some cells contain more than one nucleus; osteoclasts (a type of bone cell) usually contain 12 nuclei or more

The Nucleus 

The nucleus can be thought as the control center for the cell because it contains the instructions to make proteins, and proteins can then make other molecules needed for cellular function and survival 

The nucleus contains DNA, which contains genes. Genes contain the instructions for cellular function and survival. For example, the insulin gene contains instructions to make insulin protein. There are also genes that contain instructions for enzymes that are then used to make other molecules necessary for cellular function. In addition, genes are units of inheritance that pass information from parents to their children 

The nucleus is also the site for the synthesis of three main types of ribonucleic acid (RNA). These RNA molecules move from the nucleus to the cytoplasm and carry out the synthesis of proteins. These three types of RNA are as follows: 

Messenger RNA (mRNA), which is made from genetic information transcribed from DNA in a process called transcription, mRNA travels to ribosomes in the cytoplasm so these instructions can be used to make proteins 

Ribosomal RNA (rRNA), is the RNA component of ribosomes, the site of proteins production 

Transfer RNA (tRNA), transports amino acids to ribosomes so that mRNA can be turned into a sequence of amino acids. This process, known as translation, uses the mRNA template to link amino acids to synthesize proteins 

The nucleoplasm inside the nucleus is separated from the cytoplasm outside of the nucleus by the nuclear envelope that surrounds the nucleus. The nuclear envelope contains many nuclear pores. Fluids, electrolytes, RNA, some proteins, and some hormones move in both directions through the nuclear pores, and this exchange between the nucleoplasm and cytoplasm appears to be regulated

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[multidrug-resistant-organisms]

Common ECG Changes Due to Electrolyte Imbalances

The most common and clinically relevant electrolyte imbalances include potassium, calcium, and magnesium. Note that some patients may exhibit combined electrolyte imbalances. 

Sodium 

Hypo and hypernatremia have no effect on the ECG, no cardiac rhythm, impulse, or conduction 

Calcium 

Hypercalcemia 

Primary hyperparathyroidism and malignancies cause 90% of all hypercalcemia. Less common are immobilization, sarcoidosis, thyrotoxicosis, familial hypocalciuric hypercalcemia, Addison’s disease, renal failure, tamoxifen, lithium, thiazide diuretics, vitamin D and calcium overdose 

Common ECG Changes 

Shortened QT interval 

Lengthened QRS duration

Bradycardia

Hypocalcemia 

Causes of hypocalcemia include acute pancreatitis, pancrea surgery, alkalosis (hypoventilation), rhabdomyolysis, sepsis, osteolytic cancer metastases, abnormal calcium absorption (GI) and resorption (urinary), renal failure, small bowel syndrome, parathyroid gland surgery, use of bisphosphonates, excess calcitonin, use of phenytoin, use of phosphate substitution , and use of foscarnet 

Common ECG Changes 

Lengthened QT interval (torsade de pointes is uncommon) 

Shortened QRS duration (has no clinical significance) 

Potassium 

Potassium plays a key role in both depolarization and repolarization, which is why potassium imbalances may cause dramatic ECG changes. These are of utmost clinical significance. There is a rather strong correlation between serum potassium level and ECG changes, as well as risk of arrhythmia. 

Hyperkalemia - severe symptoms generally occur at 7 mmol/L or higher 

Severe hyperkalemia is usually the result of several interacting factors such as renal failure, insufficient corticosteroid substitution, acidosis, hemolysis, and massive muscle damage. Potassium substitution may be the etiology. Potassium-sparing diuretics, ACE inhibitors, and ARBs may also cause hyperkalemia. Insulin deficiency, Addison’s disease, and digoxin toxicity may also cause hyperkalemia 

Common ECG Changes 

The earliest sign of hyperkalemia is pointed T-waves. Pointed T-waves are tall and narrow at the top 

P-waves that become wider. P-wave amplitude decreases. The P-wave may be difficult to discern

Prolonged PR interval. Occasionally SA block, second- or third-degree AV block may develop 

ST segment elevation may occur in leads V1-V3 

Potassium greater than 7.5; QRS complex becomes wider 

Hypokalemia - serious complications may occur at 3 mmol/L and below 

Causes of hypokalemia include diarrhea, excess vomiting, malnutrition, acute medical illness, primary or secondary aldosteronism, excess intake of licorice, glucose infusion, diuretics, adrenergic agonists, theophyllamine, corticosteroids, and insulin 

Common ECG Changes 

T-waves become wider with lower amplitude.T-wave inversion may occur in severe hypokalemia 

ST segment depression develops and may, along with  T-wave inversions, simulate ischemia  

P-wave amplitude, P-wave duration, and PR interval may all increase

U-waves emerge. U-waves are best seen in leads V2-V3. If the hypokalemia is severe enough, the U-wave may become larger than the T-wave

Hypokalemia may cause acquired long QT syndrome and predisposes to torsade de pointes (polymorphic ventricular tachycardia)

Hypokalemia may also cause monomorphic ventricular tachycardia

Hypokalemia potentiates the proarrhythmic effects of digoxin 

Magnesium 

Hypermagnesemia is rare but severe hypermagnesemia may cause AV and intracellular conduction disturbances, which may culminate in third-degree AV block or asystole 

Hypomagnesemia may potential the proarrhythmic effect of digoxin. Hypomagnesemia may also predispose to supraventricular and ventricular tachyarrhythmias 

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Management of Ventricular Tachycardia

Sustained vs. Nonsustained��ventricular tachycardia: ventricular tachycardia with duration less than 30 seconds is classified as nonsustained. Sustained ventricular tachycardia has a duration of more than 30 seconds

Monomorphic ventricular tachycardia: all QRS complexes display the same morphology (minor differences are allowed).This indicates that the impulses originate in the name ectopic focus. In structural heart disease (CAD, HF, cardiomyopathy, valvular disease, etc.) monomorphic ventricular tachycardia is typically caused by re-entry. 

Polymorphic ventricular tachycardia: QRS complexes with varying morphology or varying electrical axis. The rhythm may be irregular. Polymorphic ventricular tachycardia is typically very fast (100-320 beats per minute) and unstable. There are several types of polymorphic ventricular tachycardia. The most common cause is myocardial ischemia. The second most common cause is prolonged QTc interval (Long QT syndrome). 

Treatment in the emergency setting

Unconscious patients: start CPR immediately. 

Hemodynamically unstable patients (hypotension, angina, heart failure, shock, presyncope/syncope): the patient should be treated immediately with electrical cardioversion (during anesthesia). 

Beta-blockers are administered intravenously, unless the patient has bradycardia induced ventricular tachycardia. In this scenario, amiodarone is preferred after cardioversion) 

Hypokalemia and hypomagnesaemia should be corrected rapidly 

Causes underlying the ventricular tachycardia must be targeted; heart failure, ischemia, hypotension, hypokalemia, etc. can be treated rapidly. 

Hemodynamically stable patients may be treated pharmacologically with amiodarone, lidocaine, sotalol, or procainamide. Only one of these drugs are administered and a loading dose is followed by an infusion.

Amiodarone is the primary choice with a loading dose of 150 mg IV bolus over 10 minutes. An infusion at 1 mg/min over 6 hours, followed by 0.5mg/min over 18 hours. The loading dose may be repeated every 10-15 minutes if needed. The maximum dose of amiodarone is 2.2 g/day. If amiodarone fails, electrical cardioversion should be considered before pharmacological alternatives are considered. 

Intermittent ventricular tachycardia with frequent capture beats should be treated pharmacologically. 

Polymorphic ventricular tachycardia should be considered unstable and treated immediately with electrical cardioversion. Beta-blockers may be administered if the ECG does not show long QT interval. If the ECG does show long QT interval, the condition is classified as torsade de pointes, for which  treatment varies: 

Torsade de pointes in a hemodynamically stable patient

Magnesium sulfate 1g is given over 60 seconds, repeated every 5-10 minutes if indicated. If continuous infusion is necessary, the does is 5-10 mg/min. 

All medications/drugs that may cause or aggravate the arrhythmia must be stopped. 

Potassium infusion in patients with hypokalemia. 

Correction of bradycardia; atropine IV 1-2 mL at 0.5 mg/mL. Isoprenaline (isoproterenol) may also be used, 0.01 mcg/kg/min, which is titrated up until bradycardia resolves. Note that isoprenaline must be administered carefully because it activates beta adrenergic receptors, which may aggravate the arrhythmia.

Temporary transcutaneous or transvenous pacemaker. 

Torsade de pointes with hemodynamic compromise 

Start with 150 J (biphasic shock) and increase by 50 J for each shock 

Ventricular fibrillation and cardiac arrest is treated with conventional resuscitation 

Long-term treatment of ventricular tachycardia: patients with preserved LV function and asymptomatic nonsustained ventricular tachycardias may be adequately treated with beta-blockers. Sotalol (may cause QT prolongation) and amiodarone may be considered. Verapamil is contraindicated. If the individual has suffered a MI, and ICD should be considered. Amiodarone appears to be the most effective drug in preventing new episodes of ventricular tachycardia. 

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Interpreting ECGs - The Basics

ECG interpretation traditionally starts with an assessment of the P-wave. The P-wave reflects atrial depolarization (activation). The P-wave is a small, positive, and smooth wave. It is small because the atria make up a relatively small portion of the heart’s muscle mass.

If the atria are depolarized by impulses generated by cells outside of the SA node (by an ectopic focus), the morphology of the P-wave may differ from the P-waves in sinus rhythm. If the ectopic focus is located near the SA node, the P-wave will have a morphology similar to the P-wave in sinus rhythm. However, an ectopic focus may be located anywhere. If is it located near the AV node, the activation of the atria will proceed in the opposite direction, which produced an inverted (retrograde) P-wave.

The PR interval is the distance between the onset of the P-wave to the onset of the QRS complex. The PR interval is assessed in order to determine whether impulse conduction from the atria to the ventricles is normal. It reflects the time interval from the start of atrial depolarization to the start of ventricular depolarization. The PR interval is assessed in order to determine whether impulse conduction from the atria to the ventricles is normal in terms of speed. The PR interval must not be too long nor too short. A normal PR interval ranges between 0.12 seconds to 0.22 seconds

The flat line between the end of the P-wave and the onset of the QRS complex is called the PR segment and it reflects the slower impulse conduction through the atrioventricular (AV) node. The PR segment serves as the baseline (also referred to as the refrence line or isoelectric line) of the ECG curve. The amplitude of any deflection (wave) is measured by using the PR segment as the baseline. Numerous conditions can diminish the capacity of the AV node to conduct the atrial impulse to the ventricles. As the conduction diminishes, the PR interval becomes longer. When the PR interval exceeds 0.22 seconds, first-degree AV-block is manifest. 

The term “block” is somewhat misleading since it is actually a matter of abnormal delay and not a block, per se.  

The AV node is normally the only connection between the atria and the ventricles. The atria and the ventricles are electrically isolated from each other by fibrous rings (anulus fibrosus). However, it is not rare to have an additional - accessory - pathway between the atria and the ventricles. Such an accessory pathway may be located almost anywhere between the atria and the ventricles. It enables the atrial impulse to pass directly to the ventricles and start ventricular depolarization prematurely. If the atrial impulse uses an accessory pathway, the impulse delay in the AV node is bypassed and therefore the PR interval becomes shortened (less than 0.12 seconds). This condition is referred to as pre-excitation because the ventricles are excited prematurely. 

The QRS complex represents the depolarization (activation) of the ventricles. It is always referred to as the “QRS complex” although it may not always display all 3 waves. Since the electrical significance generated by the left ventricle (LV) is many times larger than the electrical significance produced by the right ventricle (RV), the QRS complex is actually a reflection of LV depolarization. 

The QRS duration is the time interval from the onset to the end of the QRS complex. A short QRS complex is desirable as it proves that the ventricles are depolarized rapidly, which in turn implies that the conduction system is functioning properly. Wide (also referred to as “broad”) QRS complexes indicate that ventricular depolarization is slow, which may be due to dysfunction in the conduction system. 

The ST segment corresponds to the plateau phase (phase II) of the action potential. The ST segment must always be studied carefully since a wide range of conditions can alter it. In particular, in the setting of acute myocardial ischemia, the ST segment will be “deviated” in 2 types, either depression or elevation. 

ST segment depression implies that the ST segment is displaced, such that it is below the level of the PR segment. 

ST segment elevation implies that the ST segment is displaced, such that it is above the level of the PR segment 

The J point is the point where the ST segment starts. The magnitude of depression or elevation is measured as the height difference (in millimeters) between the J point and the PR segment. 

The T-wave reflects the rapid repolarization of contractile cells (phase III). T-wave changes also occur in a wide range of conditions. The transition from the ST segment to the T-wave should be smooth, and not abrupt. The normal T-wave is slightly asymmetric, with a steeper downward slope. 

P-Wave Checklist 

The P-wave is positive (not inverted)

P-wave duration should be less than or equal to 0.12 seconds

PR Interval Checklist 

A normal PR interval is 0.12 to 0.22 seconds 

A prolonged PR interval (> 0.22 seconds) is consistent with a first-degree AV block 

A shortened PR interval ( < 0.12 seconds) indicates pre-excitation (presence of an accessory pathway) 

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