Pulmonary Nodule

 

PULMONARY NODULE

Evaluation is guided by nodule size & assessment of probability of malignancy. In addition is based on the yield of available diagnostic testing, patient comorbidities, & patient preferences. Focal pulmonary lesions that are > 3 cm in diameter are called lung masses & should be considered malignant until proven otherwise.

Pulmonary nodules are categorized as small solid (<8 mm), larger solid (≥8 mm), and subsolid.

Subsolid nodules are divided into ground-glass nodules (no solid component) and part-solid (both ground-glass and solid components).

The probability of malignancy is less than 1% for all nodules smaller than 6 mm and 1% to 2% for nodules 6 mm to 8 mm.

Nodules that are 6 mm to 8 mm can be followed with a repeat chest CT in 6 to 12 months, depending on the presence of patient risk factors and imaging characteristics associated with lung malignancy, clinical judgment about the probability of malignancy, and patient preferences.

The treatment of an individual with a solid pulmonary nodule 8 mm or larger is based on the estimated probability of malignancy; the presence of patient comorbidities, such as chronic obstructive pulmonary disease and coronary artery disease; and patient preferences. Management options include surveillance imaging, defined as monitoring for nodule growth with chest CT imaging, positron emission tomography-CT imaging, nonsurgical biopsy with bronchoscopy or transthoracic needle biopsy, and surgical resection.

Part-solid pulmonary nodules are managed according to the size of the solid component.

Larger solid components are associated with a higher risk of malignancy.

Ground-glass pulmonary nodules have a probability of malignancy of 10% to 50% when they persist beyond 3 months and are larger than 10 mm in diameter.

A malignant nodule that is entirely ground glass in appearance is typically slow growing.

Current bronchoscopy and transthoracic needle biopsy methods yield a sensitivity of 70% to 90% for a diagnosis of lung cancer.

Infographics

Hyperparathyroidism

The most common cause of hyperparathyroidism is Parathyroid adenoma. Another cause is hyperplasia of the parathyroid glands.

Parathyroid hormone (PTH) increases serum calcium by

·         Enhancing distal tubular calcium reabsorption

·         Rapidly mobilizing calcium and phosphate from bone (bone resorption)

·         Increasing intestinal absorption of calcium by stimulating conversion of vitamin D to its most active form, calcitriol

Hyperparathyroidism is characterized as:

·         Primary: Excessive secretion of PTH due to a disorder of the parathyroid glands

·         Secondary: Hypocalcemia due to non-parathyroid disorders leads to chronic PTH hypersecretion

·         Tertiary: Autonomous secretion of PTH unrelated to serum calcium concentration in patients with long-standing secondary hyperparathyroidism

Primary hyperparathyroidism: excessive secretion of PTH by one or more parathyroid glands. Incidence increases with age and is higher in postmenopausal women. Primary hyperparathyroidism causes hypercalcemia, hypophosphatemia, and excessive bone resorption (leading to osteoporosis).

Secondary hyperparathyroidism occurs most commonly in advanced chronic kidney disease when decreased formation of active vitamin D in the kidneys and other factors lead to hypocalcemia and chronic stimulation of PTH secretion. Hyperphosphatemia that develops in response to chronic kidney disease also contributes. Other less common causes of secondary hyperparathyroidism include

·         Decreased calcium intake

·         Poor calcium absorption in the intestine due to vitamin D deficiency

·         Excessive renal calcium loss due to loop diuretic use

·         Inhibition of bone resorption due to bisphosphonate use

Tertiary hyperparathyroidism results when PTH secretion becomes autonomous of serum calcium concentration and generally occurs in patients with long-standing secondary hyperparathyroidism, as in patients with ESRD of several years’ duration.

Indications of surgery:

·         Serum calcium 1 mg/dL greater than the upper limits of normal

·         Calciuria > 400 mg/day

·         Creatinine clearance < 60 mL/minute

·         Peak bone density at the hip, lumbar spine, or radius 2.5 SD below controls (T score = −2.5)

·         Age < 50 years

·         The possibility of poor adherence with follow-up

Secondary hyperparathyroidism in patients with renal failure can result in a number of symptoms, including

·         Osteitis fibrosa cystica with arthritis, bone pain, and pathologic fractures

·         Spontaneous tendon rupture

·         Proximal muscle weakness

·         Extra-skeletal calcifications, including soft tissue and vascular calcification

·         Pruritis

Infographics

Oxygen Delivery Methods

Total O2 content is expressed by the following equation:

O2 content (CaO2) = (Hgb x 1.34 x SaO2) + (0.0031 x PaO2)

where Hgb is hemoglobin concentration and SaO2 is hemoglobin saturation at the given PO2. 

The principal form of oxygen transport in blood is as hemoglobin-bound.

Each gram of hemoglobin can maximally bind 1.34 mL of oxygen.

The oxygen-carrying capacity of the blood is calculated as = [Hb] x 1.34.

In a healthy person, with a hemoglobin concentration of 15 g / dL blood, the oxygen carrying capacity is 20.1 mL O2 / dL blood.

 

Oxygen transport is dependent on both respiratory and circulatory function.

Total O2 delivery (DO2) to tissues is the product of arterial O2 content and cardiac output (CO).

DO2 = CaO2 x CO

Note that arterial O2 content is dependent on PaO2 as well as hemoglobin concentration. As a result, deficiencies in O2 delivery may be due to a low PaO2, a low hemoglobin concentration, or an inadequate cardiac output.

 

The Fick equation of O2 consumption

VO2 = CO x (CaO2 – CvO2)

Oxy-hemoglobin Dissociation Curve

With a normal O2 consumption of approximately 250 ml/min and cardiac output of 5000 ml/min the normal arteriovenous difference is calculated to be about 5 ml O2/dl blood. The normal extraction ratio is approximately 25%, thus the body normally consumes only ~25% of the O2 carried on hemoglobin. When O2 demand exceeds supply, the extraction fraction exceeds 25%, and conversely, if O2 supply exceeds demand, the extraction fraction falls below 25%.

When DO2 (oxygen delivery) is moderately reduced, VO2 usually remains normal because of increased O2 extraction (meaning mixed venous O2 saturation decreases). With further reductions in the DO2, a critical point is reached beyond which VO2 becomes directly proportional to DO2. This state of supply-dependent O2 is typically associated with progressive lactic acidosis caused by cellular hypoxia.

Infographics

ST Elevation Myocardial Infarction (STEMI)

An acute ST-elevation myocardial infarction occurs due to occlusion of one or more coronary arteries, causing transmural myocardial ischemia which in turn results in myocardial injury or necrosis. MI in general can be classified from Type 1 to Type 5 MI based on the etiology and pathogenesis.

·         Type 1 MI is due to acute coronary atherothrombotic myocardial injury with plaque rupture. Most patients with STEMI and many with NSTEMI comprise this category.

·         Type 2 MI is the most common type of MI encountered in clinical settings in which is there is demand-supply mismatch resulting in myocardial ischemia. This demand supply mismatch can be due to multiple reasons including but not limited to presence of a fixed stable coronary obstruction, tachycardia, hypoxia or stress. Other potential etiologies include coronary vasospasm, coronary embolus, and spontaneous coronary artery dissection (SCAD).

·         Type 3 MI include patient with Sudden cardiac death who succumb before any troponin elevation comprise.

·         Types 4 and 5 MIs are related to coronary revascularization procedures like PCI or CABG.

The American College of Cardiology, American Heart Association, European Society of Cardiology, and the World Heart Federation committee established the following ECG criteria for ST-elevation myocardial infarction STEMI:

·         New ST-segment elevation at the J point in 2 contiguous leads with the cutoff point as greater than 0.1 mV in all leads other than V2 or V3

·         In leads V2-V3 the cutoff point is greater than 0.2 mV in men older than 40 years old and greater than 0.25 in men younger than 40 years old, or greater than 0.15 mV in women

Patients with a pre-existing left bundle branch block can be further evaluated using Sgarbossa's criteria:

·         ST-segment elevation of 1 mm or more that is concordant with (in the same direction as) the QRS complex

·         ST-segment depression of 1 mm or more in lead V1, V2, or V3

·         ST-segment elevation of 5 mm or more that is discordant with (in the opposite direction) the QRS complex

Infographics

Cardiomyopathies

 Cardiomyopathies are a heterogeneous group of diseases of the myocardium associated with mechanical and/or electric dysfunction that usually (but not invariably) exhibit inappropriate ventricular hypertrophy or dilatation and are due to a variety of causes that frequently are genetic. Cardiomyopathies either are confined to the heart or are part of generalized systemic disorders.

John F. Goodwin developed a classification based on structural and functional changes.

·         Congestive cardiomyopathy, now referred to as dilated cardiomyopathy (DCM),

·         Hypertrophic cardiomyopathy (HCM), and

·         Constrictive (now referred to as restrictive) cardio myopathy (RCM).

·         Arrhythmogenic right ventricular cardiomyopathy (arrhythmogenic cardiomyopathy),

Each of these categories was further subdivided by pathogenesis, such as secondary to a systemic disorder, an infection, inflammation, an inherited disorder, or idiopathic cardiomyopathies.

Infographics

Guideline-directed Medical Therapies for Heart Failure (GDMT)

 In patients with heart failure (HF), the goals of treatment are to improve their clinical condition, functional capacity, quality of life, and to prevent the events of hospital readmissions and mortality. GDMT includes the following drug therapies: renin-angiotensin-aldosterone system inhibitors (RAAS-I), with or without a neprilysin inhibitor, β-blockers, and mineralocorticoid-receptor-antagonists (MRA).

Recently, sodium-glucose cotransporter-2 inhibitors (SGLT2i) demonstrated efficacy as an important fourth pillar of GDMT. Together, this combination can add over six additional years of lifespan for HFrEF patients compared to the traditional approach of RAAS-I and β-blockers alone. However, studies highlight that many eligible HFrEF patients are not receiving one or more of the recommended medications, in the absence of contraindications or intolerance. Even among patients who are treated, less than half receive optimal doses of GDMT. Additionally, time to initiation and optimization of dosing may be exceedingly slow in the outpatient setting.

Infographics

Iron deficiency anemia

 

Iron deficiency develops in stages. In the first stage, iron requirement exceeds intake, causing progressive depletion of bone marrow iron stores. As stores decrease, absorption of dietary iron increases in compensation. During later stages, deficiency impairs RBC synthesis, ultimately causing anemia. Severe and prolonged iron deficiency also may cause dysfunction of iron-containing cellular enzymes.

Iron deficiency anemia is classically described as a microcytic anemia. The differential diagnosis includes thalassemia, sideroblastic anemias, some types of anemia of chronic disease, and lead poisoning. Serum ferritin is the preferred initial diagnostic test. Total iron-binding capacity, transferrin saturation, serum iron, and serum transferrin receptor levels may be helpful if the ferritin level is between 46 and 99 ng per mL (46 and 99 mcg per L); bone marrow biopsy may be necessary in these patients for a definitive diagnosis.

 

The diagnosis of IDA requires that a patient be anemic and show laboratory evidence of iron deficiency. Red blood cells in IDA are usually described as being microcytic (i.e., mean corpuscular volume less than 80 μm3 [80 fL]) and hypochromic, however the manifestation of iron deficiency occurs in several stages. Patients with a serum ferritin concentration less than 25 ng per mL (25 mcg per L) have a very high probability of being iron deficient. The most accurate initial diagnostic test for IDA is the serum ferritin measurement. Serum ferritin values greater than 100 ng per mL (100 mcg per L) indicate adequate iron stores and a low likelihood of IDA

Infographics

Tumor lysis syndrome

Tumor lysis syndrome is a clinical condition that can occur spontaneously or after the initiation of chemotherapy associated with the following metabolic disorders: hyperkalemia, hyperphosphatemia, hypocalcemia, and hyperuricemia leading to end-organ damage. It is most common in patients with solid tumors. Tumor lysis syndrome usually develops after the initiation of chemotherapy treatment. However, there are more cases of spontaneous development of tumor lysis syndrome with high-grade hematology-oncology malignancies.

Hallmarks of this condition

• Potassium >6.0 meq/L or a 25% increase from baseline
• Phosphorous >4.5 mg/dL or a 25% increase from baseline
• Calcium <7 mg/dL or a 25% decrease from baseline
• Uric acid >8 mg/dL or a 25% increase from baseline

Clinical tumor lysis syndrome:

• Creatinine greater than 1.5 times normal
• Cardiac arrhythmia/sudden death
• Seizure

Most of the symptoms seen in patients with tumor lysis syndrome are related to the release of intracellular chemical substances that cause impairment in the functions of target organs. This can lead to acute kidney injury (AKI), fatal arrhythmia, and even death.

In patients at low risk for developing TLS, management includes hydration and close monitoring of volume status and renal function. The use of urine alkalinization to promote elimination of urate is not recommended because it can induce calcium phosphate deposition and therefore aggravate TLS.
In patients at intermediate risk with uric acid levels lower than 8 mg/dl, a xanthine oxidase inhibitor such as allopurinol also should be started 2 days before chemotherapy, whereas rasburicase should be used in patients with uric acid levels higher than 8 mg/dl. 

Rasburicase should not be used in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. For high-risk patients, a single dose of rasburicase (up to 0.2 mg/kg, although a lower dose is usually prescribed) is recommended, followed by close monitoring of uric acid levels. If uric acid normalizes, allopurinol treatment can be started. If urine output decreases despite adequate fluid administration, a loop diuretic should be added, and RRT will be required if oliguria persists.

Infographics