QT/QTc- Interval

• Start of Q-wave to end of the T-wave (time of ventricular depolarization + repolarization). 
• Life threatening risk of prolonged QTc >500ms = Torsades de pointes (TdP).
• Prolonged QT/QTc interval may be a clue to electrolyte disturbances (hypocalcemia or hypokalemia), drug effects (quinidine, procainamide, amiodarone, or sotalol), or myocardial ischemia (usually with prominent T wave inversions). 
• Shortened QT intervals are seen with hypercalcemia and digitalis effect. 
• Each 10-millisecond increase in QTc contributes approx a 5% to 7% additional increase in risk for TdP.
• QTc of 540 milliseconds has a 63% to 97% higher risk of developing TdP than a patient with QTc of 440 milliseconds.

How do you measure it:

• Find a lead with the tallest T wave and count the little boxes from the start of the QRS complex to the point where the T wave comes back down to the isoelectric line. 
• Multiply the number of little boxes by 0.04 seconds. 
• Example if you counted 8 boxes then QT interval is 8 x 0.04 = 0.32 seconds (320 milliseconds).
• QT interval should be less than half the preceding R-R interval (Works for regular rates between 65-90).

Methods of calculating the QTc:

• Bazett formula, QTc = QT / √RR.  
• Fridericia formula (QTc = QT / RR1/3)
• Hodges [QTc = QT + 0.00175 x (HR - 60)]
• Framingham linear regression analysis {QTc = QT + 0.154 x (1 - RR)}
• Karjalainen et al. [QT nomogram] 
• Rautaharju formula, QTc = QT x (120 + HR) / 180

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Rhabdomyolysis

• Rhabdomyolysis is a clinical syndrome that comprises destruction of skeletal muscle with outflow of intracellular muscle content into the bloodstream. 
• The systemic complications associated with rhabdomyolysis result from the leakage of muscle intracellular components into the bloodstream. 
• Elevated Creatine kinase (CK) hallmark of rhabdomyolysis. 
• Defined based on CK values five times above the upper limit of normal. 
• Half-life of CK is 1.5 days; elevated<12hrs, peaks in 3 days, & normalizes in 5 days. 
• Myoglobin half-life of 2-3 hrs & rapidly excreted by kidneys. 
• Rapid & unpredictable metabolism makes myoglobin less useful marker of muscle injury.
• Antibiotics associated with rhabdomyolysis: Daptomycin, macrolides, trimethoprim-sulfamethoxazole, linezolid, fluoroquinolones, and cefdinir. 
• Rhabdomyolysis is associated with hyperkalemia, hypocalcemia, hyperuricemia, and hyperphosphatemia.

Management includes appropriate hydration to improve end-organ perfusion, close monitoring of urine output, correction of electrolyte abnormalities, identification of complications like compartment syndrome, and disseminated intravascular coagulation.

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Evaluation of Leukocytosis:

Evaluation of Leukocytosis: The term 'leukocyte' applies to any cells within the myeloblast, monoblast, & lymphoid lineages. Include granulocytes (neutrophils, eosinophils, & basophils), monocytes, & lymphocytes (B cells, T cells, and natural killer cells). In adults, leukocytosis often defined as white blood cell (WBC) count > 11 × 109/L.

Mature WBC:

• 80-90% remain in storage in bone marrow.
• 2% to 3% circulate freely in peripheral blood;
• The rest stay deposited along the margins of blood vessel walls or in the spleen
• Life span: 2- 16 days (depending on cell type in the peripheral circulation).

LEUCOCYTOSIS WBC > 11,000 per mm3 [11.0 × 109 per L] Reactive: Typically, 11,000 to 30,000 per mm3. Leukemoid reaction: approx. 50,000-100,000 per (e.g., C difficile infection, sepsis, organ rejection, or solid tumors. Leukemias or myeloproliferative disorders: > 100,000 per mm3. Paradoxical neutropenia: typhoid fever, rickettsia infections, brucellosis, & dengue.

Neutrophil bands

• Immature neutrophils
• Morphologically: absence of complete separation of nuclear lobes with a visible distinction between chromatin & parachromatin in the narrowest segment of the nucleus often flagged on 5-part automated differential & confirmed by PBS.

Leukemoid Reaction:  Transient increase in WBC count defined as significant neutrophilia >50x10^9/L in the absence of a myeloproliferative neoplasm. Mature neutrophils seen in a leukemoid reaction. Etiology: sepsis, organ rejection, solid tumors, and bacterial infections. D/D leukemia: increases in blast cells (precursor cells to leukocytes) and immature WBCs, Improves after treating the underlying cause.

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Hyponatremia

Hyponatremia (<135 mEq/L) is a common electrolyte abnormality caused by an excess of total body water in comparison to that of the total body sodium content. Measuring the serum osmolality, urine sodium concentration and urine osmolality helps to differentiate among the possible causes. The severity of this electrolyte abnormality ranges from asymptomatic to seizures, coma and death as a consequence of cerebral swelling.

Pseudohyponatremia is due to hypertriglyceridemia or multiple myeloma. In regular subjects, the plasma water is 93% of the plasma volume. Plasma water part falls lower than 80% in cases with noticeable hyperlipidemia (triglycerides >1500 mg/dL) or hyperproteinemia (protein >10 mg/dL). Rise in blood urea causes the hyponatremia in renal failure.

True hyponatremia is having a fall in serum osmolality and is divided into hypervolemic, hypovolemic, and euvolemic based on volume status. 

Osmoreceptors in the hypothalamus detect the plasma osmolality. If Posm >285 mOsm/kg, osmoreceptors stimulate the release of anti-diuretic hormone (ADH) from the posterior pituitary into the circulation, as well as stimulate thirst. ADH release is also stimulated in states of low effective circulating volume. Circulating ADH binds to receptors on the principal cells of the collecting duct in the kidneys and activates a cellular pathway which ultimately results in water reabsorption. This results in a decrease in the serum osmolality and an increase in the urine osmolality (Uosm).  In certain states, ADH can be released inappropriately or ectopically, meaning that ADH is released without an osmotic or hemodynamic stimulus. When ADH is suppressed, water is renally excreted. 

Another important physiological pathway is the renin-angiotensin-aldosterone system (RAAS). This pathway is activated in states of low effective circulating volume and/or when there is reduced sodium in the renal tubules. These conditions stimulate the release of renin from the juxtaglomerular cells, which are part of the afferent arterioles. The activation of RAAS ultimately results in increased sodium reabsorption, arteriolar vasoconstriction and release of ADH from the posterior pituitary. Measured urine sodium concentration (UNa) is a reflection of intravascular volume; UNa is elevated with volume expansion and reduced with volume depletion. 

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Para-neoplastic dermatoses (PD)

Para-neoplastic dermatoses (PD):

• Heterogeneous, rare, acquired diseases characterized by the presence of an underlying neoplasia.
• Usually develop simultaneously with the underlying cancer, but they can also occur before or after the development of the neoplasia.
• Their recognition can lead to a prompt cancer detection and to an early start of the appropriate therapy.

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Diabetic Ketoacidosis (DKA)

Diagnostic Criteria:

• Serum glucose >250 mg/dL
• Arterial pH <7.3
• Serum bicarbonate <18 mEq/L
• At least moderate ketonuria or ketonemia.

10% to 30% of DKA cases occur in patients with type 2 diabetes, in situations of extreme physiologic stress or acute illness.

Infection is a very common trigger for DKA in patients who have new-onset diabetes and previously established diabetes. If there is any suspicion of infection, antibiotics should be administered promptly.

2.6% to 3.2% of DKA admissions are Euglycemic Diabetic ketoacidosis (EDKA).

Pregnancy is a risk factor for EDKA because of the physiologic state of hypoinsulinemia and increased starvation.
Alcoholic ketoacidosis may have a similar presentation to EDKA, with anorexia, vomiting, dyspnea, and significant anion gap metabolic acidosis and ketonemia.

Common, early signs of ketoacidosis include nausea, vomiting, abdominal pain, and hyperventilation.

Patients with DKA usually present with a serum anion gap greater than 20 mEq/L (normal 3 to 10 mEq/L). However, the increase in anion gap is variable, being determined by several factors: the rate and duration of ketoacid production, the rate of metabolism of the ketoacids and their loss in the urine, and the volume of distribution of the ketoacid anions.

Continue insulin infusion until ketoacidosis is resolved, serum glucose is below 200 mg/dL, and subcutaneous insulin is begun. Treatment with IV fluid resuscitation should continue until the anion gap closes and acidosis has resolved.

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Pemphigus

 Pemphigus vulgaris (PV) is an autoimmune, intraepithelial, blistering disease affecting the skin and mucous membranes. It is mediated by circulating autoantibodies against keratinocyte cell surfaces. Exposure to certain medications like penicillamine and captopril can trigger PV. Such a trigger can happen through the effects on binding to molecules involved in cell adhesion, influence on enzymes that mediate keratinocyte aggregation, and molecules involved in cell and by stimulating neoantigen formation. In addition, NSAID’s, penicillin, cephalosporins have been associated with drug-induced PV.

IgA pemphigus does not present with oral mucosa blisters. Direct and indirect immunofluorescence can both help to differentiate PV from IgA pemphigus.

Pemphigus foliaceus does not affect the oral mucosa and is less common than PV.

Paraneoplastic pemphigus presents with mucocutaneous vesicles and bullae and can be differentiated from PV using indirect immunofluorescence and immunoblot.

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Zephyr Endobronchial Valve

The Zephyr Endobronchial Valve is an endobronchial implant designed to occlude a hyperinflated lobe of the lungs with multiple valves, allowing air to escape while blocking airflow into the treated lobe. This is intended to result in a reduction in lung volume and hyperinflation in the targeted area. This one-way valve therapy leads to an improvement of lung function, exercise tolerance, and quality of life in patients with advanced emphysema.

Key inclusion criteria:

• Severe emphysema: forced expiratory volume in 1 second (FEV1) ≤ 45% of predicted, TLC ≥ 100% of predicted, RV ≥ 150% of predicted
• Resting partial pressure of arterial carbon dioxide (Paco2) ≤ 60 mm Hg
• Resting partial pressure of arterial oxygen (Pao2) on room air ≥ 45 mm Hg
• Body mass index ≤ 31 kg/m2 for men, ≤ 32 kg/m2 for women
• Abstinence from smoking for at least six months
• Completion of pulmonary rehabilitation.

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