Hypermagnesemia

 Hypermagnesemia occurs primarily in patients with acute or chronic kidney disease. In these individuals, some conditions, including proton pump inhibitors, malnourishment, and alcoholism, can increase the risk of hypermagnesemia. Hypothyroidism and especially cortico-adrenal insufficiency, are other recognized causes.

Hyperparathyroidism and alterations in calcium metabolism involving hypercalcemia and/or hypo-calciuria can lead to hypermagnesemia through an increased calcium-induced magnesium absorption in the tubule. Patients with familial hypocalciuric hypercalcemia (FHH), a rare autosomal dominant condition, can manifest hypermagnesemia.

Lithium-based psychotropic drugs can also lead to hypermagnesemia by reducing excretion. Patients with milk-alkali syndrome due to the ingestion of large amounts of calcium and absorbable alkali are more susceptible to develop hypermagnesemia. Magnesium levels can increase in hemolysis patients. Red blood cells contain three times as much magnesium as compared to plasma. The rupture of these cells pours magnesium into the plasma. However, symptomatic hypermagnesemia occurs only in the case of aggressive hemolysis. Tumor lysis syndrome, rhabdomyolysis, and acidosis (e.g., decompensated diabetes with ketoacidosis) can also induce hypermagnesemia through extracellular shifts.

Summary:

• Mild hypermagnesemia (less than 7 mg/dL) - Asymptomatic or pauci-symptomatic: weakness, nausea, dizziness, and confusion
• Moderate hypermagnesemia (7 to 12 mg/dL) - Decreased reflexes, worsening of the confusional state and sleepiness, bladder paralysis, flushing, headache, and constipation. A slight reduction in blood pressure, bradycardia, and blurred vision caused by diminished accommodation and convergence are usually present.
• Severe hypermagnesemia (greater than 12 mg/dL) - Muscle flaccid paralysis, decreased breathing rate, more evident hypotension and bradycardia, prolongation of the P-R interval, atrioventricular block, and lethargy are common. Coma and cardiorespiratory arrest can occur for higher values (over 15 mg/dL).

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Calcium metabolism and management

Ionized calcium is the physiologically active form. Ionized calcium acts as an intracellular 2nd messenger; it is involved in skeletal muscle contraction, excitation-contraction coupling in cardiac and smooth muscle, and activation of protein kinases and enzyme phosphorylation. Calcium is also involved in the action of other intracellular messengers, such as cAMP (cyclic adenosine monophosphate) and inositol 1,4,5-triphosphate, and thus mediates the cellular response to numerous hormones, including epinephrine, glucagon, vasopressin (antidiuretic hormone), secretin, and cholecystokinin.

Despite its important intracellular roles, about 99% of body calcium is in bone, mainly as hydroxyapatite crystals. About 1% of bone calcium is freely exchangeable with the extracellular fluid and, therefore, is available for buffering changes in calcium balance.

Normal total serum calcium concentration ranges from 8.8 to 10.4 mg/dL. About 40% of the total blood calcium is bound to plasma proteins, primarily albumin. The remaining 60% includes ionized calcium plus calcium complexed with phosphate and citrate. Total calcium (ie, protein-bound, complexed, and ionized calcium) is usually what is determined by clinical laboratory measurement.

However, ideally, ionized (or free) calcium should be estimated or measured because it is the physiologically active form of calcium in plasma and because its blood level does not always correlate with total serum calcium.

Ionized calcium is generally assumed to be about 50% of the total serum calcium.

Ionized calcium can be estimated, based on total serum calcium and serum albumin levels. Direct determination of ionized calcium, because of its technical difficulty, is usually restricted to patients in whom significant alteration of protein binding of serum calcium is suspected.

Normal ionized serum calcium concentration range varies somewhat between laboratories, but is typically 4.7 to 5.2 mg/dL.

 The regulation of both calcium and phosphate balance is greatly influenced by concentrations of circulating PTH, vitamin D, and, to a lesser extent, calcitonin. Calcium and phosphate concentrations are also linked by their ability to chemically react to form calcium phosphate. The product of concentrations of calcium and phosphate (in mg/dL) is estimated to be < 60 mg2/dL2 (< 4.8 mmol2/L2) normally; when the product exceeds 70 mg2/dL2 (5.6 mmol2/L2), precipitation of calcium phosphate crystals in soft tissue is much more likely. Calcification of vascular tissue accelerates arteriosclerotic vascular disease and may occur when the calcium and phosphate product is even lower (> 55 mg2/dL2 [4.4 mmol2/L2]), especially in patients with chronic kidney disease.

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Aortic Aneurysms

 Abdominal Aortic Aneurysms

• Abdominal aortic aneurysms are much more common than thoracic aortic aneurysms.
• Age is an important risk factor, and the incidence of abdominal aortic aneurysm rises rapidly after the age of 55 years in men and 70 in women.
• The prevalence of abdominal aortic aneurysms is ≈5% among men ≥65 years of age screened by ultrasound.
• Smoking is the risk factor most strongly associated with abdominal aortic aneurysms, followed by age, hypertension, hyperlipidemia, and atherosclerosis. Sex and genetics also influence aneurysm formation.
• Men are 10 times more likely than women to have an abdominal aortic aneurysm of 4 cm or greater.
• Those with a family history of abdominal aortic aneurysm have an increased risk of 30% and their aneurysms tend to occur at a younger age and carry a greater risk of rupture than do sporadic aneurysms.

 

Thoracic Aortic Aneurysms

• Thoracic aneurysms may involve one or more aortic segments (aortic root, ascending aorta, arch, or descending aorta) and are classified accordingly.
• Sixty percent of thoracic aortic aneurysms involve the aortic root and/or ascending aorta, 40% involve the descending aorta, 10% involve the arch, and 10% involve the thoracoabdominal aorta (with some involving >1 segment).
• The etiology, natural history, and treatment of thoracic aneurysms differ for each of these segments.

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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.

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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

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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.

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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

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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.

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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.

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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

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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.

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INGUINAL HERNIA

 

An inguinal hernia is a protrusion of abdominal or pelvic contents through a dilated internal inguinal ring or attenuated inguinal floor into the inguinal canal and usually, but not always, out of the external inguinal ring, causing a visible or easily palpable bulge.

Presents with visible or easily palpable swelling in the groin, often with discomfort during strenuous exercise or heavy lifting.

Complications are rare but include incarceration, bowel obstruction, and strangulation.

Diagnosis is usually clinical; imaging may be helpful where there is doubt about diagnosis, but also identifies many clinically insignificant apparent hernias.

Surgical repair remains the mainstay of therapy, although watchful waiting is reasonable in adults with minimally symptomatic or asymptomatic inguinal hernia.

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