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 The chemical formula of Digoxin is C41 H64 O14.

Digoxin (Cardiac glycoside) reversibly inhibits the sodium-potassium-ATPase, causing an increase in intracellular sodium and a decrease in intracellular potassium. The increase in intracellular sodium prevents the sodium-calcium antiporter from expelling calcium from the myocyte, which increases intracellular calcium. The net increase in intracellular calcium augments inotropy. Cardiac glycosides also increase vagal tone, which results in decreased conduction through the sinoatrial and atrioventricular nodes.

Life-threatening digoxin-induced arrhythmias and other toxic manifestations occur at a substantially increasing frequency as the plasma digoxin concentration rises above 2.0 ng/mL. However, toxicity is more likely in the presence of one or more comorbid conditions (eg, hypokalemia, hypomagnesemia, hypercalcemia, myocardial ischemia). Hypokalemia is a particularly important risk factor that can promote digoxin-induced arrhythmias.

PVCs are often the first sign of digoxin toxicity and are the most common arrhythmia due to digoxin toxicity. PVCs can be isolated or occur in a bigeminal pattern. The so-called "digitalis effect" on the ECG consists of T wave changes (flattening or inversion), QT interval shortening, scooped ST segments with ST depression in the lateral leads and increased amplitude of the U waves.

Early recognition of cardiac glycoside toxicity and prompt administration of Fab fragments is essential for the successful treatment of severe poisoning. Fab fragments are highly effective and safe and have transformed the management of cardiac glycoside poisoning.

 Upper Motor Neuron (UMN) lesions are lesions occurring anywhere in the CNS from the brain up to the spinal cord before the alpha motor neurons arise from the spinal cord. The lesion could arise from the cerebral cortex, internal capsule, midbrain, pons, medulla, and the cortico-spinal tract in the spinal cord.

Lower motor neuron (LMN) lesions may arise from disease processes affecting the anterior horn cell or the motor axon and/or its surrounding myelin. Neuromuscular junction pathology and muscle disorders may mimic an LMN disorder and form part of the differential diagnosis. In an LMN lesion, the muscle becomes hypersensitive to neuro-transmitter as it is denervated. Similarly, the damaged lower motor erratically discharges the neurotransmitter stored within itself as the neuron degrades. So, both increased hypersensitivity and erratic release of neurotransmitter cause fasciculations. However, in UMN lesions, there is regular firing to prevent the atrophy of muscles. LMN syndromes are clinically characterized by muscle atrophy, weakness, and hyporeflexia without sensory involvement.

Neuromuscular Junctions, the junction between a motor neuron and muscle fiber is a specialized synapse. The motor neuron releases a flood of acetylcholine (Ach) neurotransmitters upon stimulation from the axon terminals from synaptic vesicles that bind with the post-synaptic receptors at the plasma membrane. This response is contractile causing muscle contraction and inhibition does not require a neurotransmitter release.

UMC & LMN lesions cause very different clinical findings.

  1. UMN lesions are lesions anywhere from the cortex to the descending tracts. This lesion causes hyperreflexia, spasticity, and a positive Babinski reflex, presenting as an upward response of the big toe when the plantar surface of the foot is stroked, with other toes fanning out.
  2. LMN lesions are lesions anywhere from the anterior horn of the spinal cord, peripheral nerve, neuromuscular junction, or muscle. This type of lesion causes hyporeflexia, flaccid paralysis, and atrophy.

 

Hemoglobin A1c (glycated hemoglobin) reflects the average blood glucose concentration over the course of the RBC lifespan, roughly 120 days in normal individuals. As the average plasma glucose increases, so does the amount of glycated hemoglobin in the plasma. Limitation of hemoglobin A1c is that it does not provide any indication of the changes in glucose concentrations throughout the day, for which frequent glucose measurements are needed.

The equation to calculate eAG (in mg/dL) from hemoglobin A1c (in %) is as follows: 

eAG (mg/dL) = 28.7 x NGSP-A1c (%) – 46.7

The Diabetes Control and Complications Trial (DCCT) reported that a higher mean A1c level was the dominant predictor of diabetic retinopathy progression. Tighter control shown by levels of HbA1c in the 7% range or lower, were correlated with 35-76% decrease in microvascular complications, like retinopathy, nephropathy and neuropathy, in patients with type 1 diabetes. The extension of DCCT into EDIC study showed benefit in the cardiovascular risk and mortality in the long-term for those patients with lower levels of HbA1c.

 A1c exhibited direct correlations with cholesterol, triglycerides, and LDL and inverse correlation with HDL cholesterol. A1c is identified as a significant risk factor for cardiovascular diseases and stroke in subjects who may have diabetes.

Women with HbA1c 5.7%–6.4% have a significantly higher risk of progression to GDM compared with women with normal HgbA1c values and should be considered for closer GDM surveillance and possible intervention.

ADA Recommendations:

Older adults who are otherwise healthy with few coexisting chronic illnesses and intact cognitive function and functional status should have lower glycemic goals (such as A1C <7.0–7.5%), while those with multiple coexisting chronic illnesses, cognitive impairment, or functional dependence should have less stringent glycemic goals (such as A1C <8.0–8.5%).

Since the lifespan of RBCs is about 120 days, glycated hemoglobin (hemoglobin A1c) represents a measurement of the average blood glucose level over the past 2 to 3 months. Serum proteins are present in the blood for a shorter time, about 14 to 21 days, so glycated proteins, and the fructosamine test, reflect average glucose levels over 2 to 3 weeks.

Instances where fructosamine may be considered over A1c include:

  1. Rapid changes in diabetes treatment
  2. Diabetic pregnancy
  3. Shortened RBC life span, such as hemolytic anemia or blood loss. When the lifespan of RBCs in circulation is shortened, the A1c result is falsely low and is an unreliable measurement of a person's average glucose over time.
  4. Abnormal forms of hemoglobin – the presence of some hemoglobin variants, such as hemoglobin S in sickle cell anemia, may affect certain methods for measuring A1c.

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) recommends against the use of the A1c test in patients with the hemoglobin variants HbSS, HbSC, or HbCC as these patients may suffer from conditions that affect the A1c test, such as anemia, increased RBC turn-over, and frequent blood transfusions.

Drug-induced gingival enlargement is a side-effect of certain drugs where the gingival tissue is not the intended target organ. The key offending drug classes are anticonvulsants, immunosuppressants, and calcium channel blockers. It is estimated that 50% of adults treated with phenytoin experience gingival enlargement, 30% with cyclosporine, and 20% with nifedipine. This overgrowth impedes proper dental hygiene and, apart from the cosmetic damage, causes painful chewing and eating. The common mechanism of action at the cellular level of all these three categories of dissimilar drugs appears to be inhibition of cation influx, particularly sodium and calcium ions. The modalities of treatment are medical and surgical. Medical management is the first line of therapy and includes discontinuing or changing the medication must be placed under consideration. Surgery is reserved for recurrences or cases that persist despite good medical treatment.

 

 

Celiac disease (CD) is an immune-mediated, multisystem disorder that affects genetically susceptible individuals who are exposed to gluten-containing grains such as wheat, barley, and rye.

Also known as gluten-sensitive enteropathy, Celiac disease is a condition in which the body responds to gluten with an inappropriate immune response causing small intestinal inflammation and damage.

CD can be associated with different autoimmune and idiopathic diseases, including type 1 diabetes mellitus, Hashimoto’s thyroiditis, selective IgA deficiency, alopecia areata, Addison’s disease, connective tissue diseases (mainly Sjogren’s syndrome), chromosomal diseases (Down, Turner, and William’s syndromes), neurological diseases (cerebellar ataxia, peripheral neuropathy, epilepsy with and without occipital calcifications), hepatic autoimmune diseases (primary biliary cholangitis, autoimmune hepatitis, primary sclerosing cholangitis), and idiopathic dilated cardiomyopathy.

Extraintestinal symptoms are common and may include:

  • Anemia due to defective absorption of vitamin B12, folate or iron
  • Coagulopathy due to impaired absorption of vitamin K
  • Osteoporosis
  • Neurological symptoms like muscle weakness, paresthesias, seizures and ataxia

Dermatitis herpetiformis is an extraintestinal manifestation that is pathognomonic for celiac disease. Because the rash is an immunologic response to gluten, it is sometimes referred to as celiac disease of the skin. This papulovesicular rash is extremely pruritic and found on extensor surfaces, such as the elbows, knees, buttocks, and scalp.

The two antibodies measured are anti-tissue transglutaminase antibodies (by enzyme-linked immunosorbent assay or ELISA measured numerically) and anti-endomysial antibodies.

Esophagogastroduodenoscopy with small bowel biopsy is recommended to confirm the diagnosis in most patients, including those with a negative serologic test for whom clinical suspicion of celiac disease persists.

Genetic testing for human leukocyte antigen alleles DQ2 or DQ8 may be performed in select cases.

A gluten-free diet for life is the primary treatment


Creatine kinase (CK) is an intracellular enzyme present in skeletal muscle, myocardium & brain; smaller amounts in visceral tissues. Released after disruption of cell membranes due to hypoxia or other injury.
Sustained increases in these levels can be a sensitive indicator of underlying muscle damage.
CK may increase to as much as 30 times the upper limit within 24 hrs of strenuous physical activity, then slowly decline over next 7 days.
The definitive diagnosis of rhabdomyolysis is reliably made by serologic testing for creatine kinase (CK). Elevated levels of CK are the hallmark of rhabdomyolysis.
CK functions as an energy reservoir for ATP:
Creatine + ATP = creatine kinase + ADP (adenosine diphosphate).
CK has a half-life of 1.5 days; its level elevated in the first 12 hours, peaks during the first 3 days, and normalizes at around 5 days after injury.
CK level five times the upper limit of normal (≈1000 U/L), without apparent cardiac or brain injury, confirms the diagnosis.
Risk of developing AKI is usually low when the CK level is below 10,000 U/L.
AKI at lower levels of CK noted with coexisting conditions, such as sepsis, hypotension, or underlying CKD.
Myoglobin levels rise rapidly (within 3 hours) and peak prior to serum CK levels.
Myoglobin has a short half-life of 2 - 3 hours and is rapidly excreted by the kidneys.
Rapid and unpredictable metabolism makes serum myoglobin a less useful marker of muscle injury than CK, and is rarely used in assessing the risk of AKI.


Bile acids are the end products of cholesterol catabolism. Cholic acid and chenodeoxycholic acid are the major primary bile acids synthesized in human livers and are conjugated with taurine or glycine for secretion into bile. Human liver synthesizes about 200 to 600 mg bile acids per day. The net daily turnover of bile acids is about 5% of a total bile acid pool of about 3 g. Conversion of cholesterol to bile acids involves 17 distinct enzymes located in the cytosol, endoplasmic reticulum, mitochondria, and peroxisome. After each meal, cholecystokinin secreted from the intestine stimulates gallbladder contraction to empty bile acids into the intestinal tract. When passing down the intestinal tract, small amounts of unconjugated bile acids are reabsorbed in the upper intestine by passive diffusion. Most bile acids (95%) are reabsorbed in the brush border membrane of the terminal ileum, trans diffused across the enterocyte to the basolateral membrane, and secreted into portal blood circulation to liver sinusoids and are taken up into hepatocytes. Bile acids lost in the feces (~0.5 g/day) are replenished by de novo synthesis in the liver to maintain a constant bile acid pool.

Bile acids stimulate glucagon-like peptide 1 (GLP1) production in the distal small bowel and colon, stimulating insulin secretion, and therefore, are involved in carbohydrate and fat metabolism. Bile acids through their insulin sensitizing effect play a part in insulin resistance and type 2 diabetes. Bile acid metabolism is altered in obesity and diabetes.


Radiological sign, a triradiate radiolucent shadow, characteristic of the automobile maker's trademark. In case of Gallstones, radiolucent lines represent gas accumulation within the body of a calculus. Center of calculus may contract more than its periphery, which would result in the radial fissures. Gas in the fissures typically comprises < 1% O2, 6–8% Co2 & the rest nitrogen.

The inverted Mercedes-Benz sign refers to the shape taken on by a spinal subdural hematoma on axial imaging at the level of the denticulate ligaments, best visualized on MRI. A pair of denticulate ligaments and the dorsal septum constitute the three radiating spikes of the sign, while blood expands and fills the three loculations in-between.

The Mercedes-Benz sign can be seen in aortic dissection on CT. It is seen as three distinct intimal flaps that have a triradiate configuration like the Mercedes-Benz logo. The appearances are postulated to represent secondary dissection in the wall of the dissected false lumen. It is also called a triple-barreled aortic dissection

Warfarin induced skin necrosis is often heralded by paresthesia, or a sensation of pressure, associated with an erythematous flush that is usually poorly demarcated. The lesions are painful, sudden, well localized and initially hemorrhagic or erythematous. In women, the site of the lesion is random and unpredictable, but the breast is the most common site, followed by the buttocks and thighs. Occasionally, the trunk, face and extremities are also involved.

The mechanism is thought to be that, following the initiation of warfarin, both protein C antigen and activity levels drop rapidly, compared with levels of other vitamin K-dependent factors such as factors IX and X, and prothrombin. This observed rapid early fall in protein C level prompted the hypothesis that the administration of warfarin to protein C-deficient individuals causes a temporary exaggeration of the imbalance between pro- coagulant and anticoagulant pathways; that is, the early suppressive action of warfarin on protein C may not be counterbalanced by the anticoagulant effect created by the decline in other vitamin K-dependent factors, thereby leading to a relative hypercoagulable state at the start of treatment. This leads to thrombotic occlusions of the microvasculature with resulting necrosis.

Exophthalmos (also known as proptosis) is the protrusion of one eye or both anteriorly out of the orbit. It derives from Greek, meaning 'bulging eyes. It occurs due to an increase in orbital contents in the regular anatomy of the bony orbit. Exophthalmos typically arises from an increase in orbital contents within the bony orbit, leading to forward displacement of the globe. The origin of the increased orbital content depends on the underlying cause. In Graves ophthalmopathy, enlargement of the extraocular muscles and expansion of the orbital adipose tissues occurs due to abnormal hyaluronic acid accumulation and edema collection into the retro-orbital space.

The etiological basis of proptosis can include inflammatory, vascular, infectious, cystic, neoplastic (both benign and malignant, metastatic disease), and traumatic factors. Some examples include infectious causations such as orbital cellulitis and subperiosteal abscesses. Traumatic causations could be orbital emphysema, retro-orbital hemorrhage, and carotid-cavernous fistula. Vascular causations not traumatically related would be orbital arteriovenous malformation (AVM) varices and aneurysms. Neoplastic causations include adenocarcinoma of the lacrimal gland, pleomorphic adenoma of the lacrimal gland, meningioma, lymphoma, and metastatic disease.

A ruptured lymphangioma can enlarge after its rupture and sequestering of heme, which pathologically is described as a chocolate cyst. Orbital varices can result in proptosis with increased venous pressure in the orbit, as seen with a Valsalva maneuver or change in postural position.


Functional obstruction may be caused by detrusor-sphincter dyssynergia (DSD), either at the level of the smooth muscle or rhabdosphincter; primary bladder neck obstruction, which may be functional and anatomic in character; or due to dysfunctional voiding, associated with learned voiding disorders or pelvic floor dysfunction associated with pain syndromes.

Anatomic obstruction in men results most commonly from benign prostatic enlargement (BPH) or urethral stricture.

Examination of historical and physical evidence of both onset and magnitude and severity of symptoms is critical in the primary evaluation of these patients. In men, benign prostatic obstruction (BPO) is the most common cause of BOO and stems from a variety of etiologies. Other causes of BOO include urethral stricture disease, dysfunctional voiding, neurogenic-based detrusor-sphincter dyssynergia (DSD), and primary bladder neck obstruction.

A normal flow rate in men does not preclude the possibility of obstruction. Concomitant analysis of flow rates and residual volumes is important to avoid misinterpretation of isolated data. Urodynamics, alternative radiologic procedures, or cystoscopy is recommended in the case of failed presumptive therapy, a complex presentation scenario, or when a diagnosis is in doubt. Formal urodynamic evaluation is usually reserved for complicated cases and is often performed in conjunction with a pressure flow evaluation.

Several artifacts can cause significant and potentially misleading alterations to measured RBC parameters:

  • Old samples cause RBCs to swell, thus increasing PCV and MCV and decreasing MCHC.
  • Lipemia causes a falsely high Hgb reading, and hence a falsely high MCHC.
  • Hemolysis causes PCV to decrease while Hgb remains unchanged, again leading to a falsely high MCHC
  • Underfilling of the tube causes RBCs to shrink, causing PCV and MCV to decrease and MCHC to increase.
  • Autoagglutination causes a falsely low RBC count, and hence a falsely high MCV.


75% happen to older women

A hip fracture is one of the most serious consequences of falls in the elderly, with a mortality of 10% at one month and 30% at one year.

There is also significant morbidity associated with hip fractures, with only 50% returning to their previous level of mobility and 10 to 20% of patients being discharged to a residential or nursing care placement.

Up to 20% of patients with hip fractures will develop a postoperative complication, with chest infections (9%) and heart failure (5%) being the most common.

Developing heart failure following a hip fracture has a very poor prognosis, with a one-year mortality of 92% and a 30-day mortality of 65%.

For chest infections, the one-year mortality is 71% and 43% within 30 days.

The effect of timing of surgical intervention on mortality remains a controversial topic. Various studies have demonstrated an improvement in mortality following early surgical intervention, but other studies did not. However, there is widespread evidence that early operative intervention does improve outcomes, including morbidity (especially infections), pressure sores, pain, and length of stay.

Named after Thomas Willis 1664, who first described the anatomy in his book "Cerebri anatome: cui accessit nervorum descriptio et usus”. Also responsible for numbering of cranial nerves, still used to this day.

The Circle of Willis is an arterial polygon (heptagon) formed as the internal carotid and vertebral systems anastomose around the optic chiasm and infundibulum of the pituitary stalk in the suprasellar cistern. This communicating pathway allows equalization of blood-flow between the two sides of the brain, and permits anastomotic circulation, should a part of the circulation be occluded.

A complete circle of Willis (in which no component is absent or hypoplastic) is only seen in 20-25% of individuals. Posterior circulation anomalies are more common than anterior circulation variants and are seen in nearly 50% of anatomical specimens.



Hemochromatosis is a disorder associated with deposits of excess iron that causes multiple organ dysfunction. Hemochromatosis has been called “bronze diabetes” due to the discoloration of the skin and associated disease of the pancreas. Hereditary hemochromatosis is the most common autosomal recessive disorder in whites. Secondary hemochromatosis occurs because of erythropoiesis disorders and treatment of the diseases with blood transfusions.

A common initial presentation is an asymptomatic patient with mildly elevated liver enzymes who is subsequently found to have elevated serum ferritin and transferrin saturation. Ferritin levels greater than 300 ng per mL for men and 200 ng per mL for women and transferrin saturations greater than 45% are highly suggestive of hereditary hemochromatosis.

Phlebotomy is the mainstay of treatment and can help improve heart function, reduce abnormal skin pigmentation, and lessen the risk of liver complications. Liver transplantation may be considered in select patients. Individuals with hereditary hemochromatosis have an increased risk of hepatocellular carcinoma and colorectal and breast cancers. Genetic testing for the hereditary hemochromatosis genes should be offered after 18 years of age to first-degree relatives of patients with the condition.



Brain natriuretic peptide

BNP is initially synthesized as a 134–amino-acid peptide called pre-pro BNP. The secondary cleaving of a 26–amino-acid signal peptide results in the formation of pro-BNP or BNP 1-108. This molecule is cleaved by furin, an endo-protease, into BNP 32 and N-terminal BNP (NT-BNP 1-76).

Major points to remember regarding BNP and NT-proBNP include:

  1. A major application of both BNP and proBNP testing is the evaluation of patients with congestive heart failure. If heart failure responds to therapy, concentrations of BNP and NT-proBNP should decline, indicating progress of therapy. If a patient does not respond, values may be increased gradually.
  2. In general, NT-proBNP is more stable (up to seven days at room temperature and up to four months if stored at −20°C) than BNP, which is not stable for a day even if the specimen is stored in a refrigerator. Therefore, BNP analysis must be performed as soon as possible after collecting the specimen.
  3. The cut-off level of BNP and NT-proBNP depends on age, as values tend to increase with advancing age. In general, heart failure is unlikely if the BNP value is less than 100 pg/mL and heart failure is very likely if the value is over 500 pg/mL. For NT-proBNP, the normal value for a person 50 years or younger is usually 125 ng/mL, but heart failure is unlikely if the NT-proBNP value is<300 pg/mL. However, heart failure is likely if the value is>450 pg/mL (>900 pg/mL in a patient of age 50 and above).
  4. Patients with end-stage renal disease and dialysis patients usually show higher BNP and NT-proBNP in serum than normal individuals.


 Pseudomonas aeruginosa and antibiotics.


Malnutrition is an imbalance between the nutrients your body needs to function and the nutrients it gets. It is an independent risk factor that negatively influences patients’ clinical outcomes, quality of life, body function, and autonomy. Early identification of patients at risk of malnutrition or who are malnourished is crucial in order to start a timely and adequate nutritional support. Nutrition support refers to enteral or parenteral provision of calories, protein, electrolytes, vitamins, minerals, trace elements, and fluids.

Historically, serum proteins such as albumin and prealbumin (i.e. transthyretin) have been widely used by physicians to determine patients’ nutritional status. Other markers that have been studied include retinol-binding protein (RBP), transferrin, total cholesterol and indicators of inflammation such as C-reactive protein (CRP) and total lymphocyte count (TLC).







Calcific aortic valve stenosis is characterized by a progressive fibro-calcific remodeling and thickening of the aortic valve cusps, which subsequently leads to valve obstruction. The underlying pathophysiology is complex and involves endothelial dysfunction, immune cell infiltration, myofibroblastic and osteoblastic differentiation, and, subsequently, calcification.

Among symptomatic patients with medically treated moderate-to-severe aortic stenosis, mortality from the onset of symptoms is approximately 25% at 1 year and 50% at 2 years. Symptoms of aortic stenosis usually develop gradually after an asymptomatic latent period of 10-20 years.

Systolic hypertension can coexist with aortic stenosis. The carotid arterial pulse typically has a delayed and plateaued peak, decreased amplitude, and gradual downslope (pulsus parvus et tardus).

Other symptoms of aortic stenosis include the following:

  • Pulsus alternans: Can occur in the presence of left ventricular systolic dysfunction
  • Hyperdynamic left ventricle: Unusual; suggests concomitant aortic regurgitation or mitral regurgitation
  • Soft or normal S1
  • Diminished or absent A2: The presence of a normal or accentuated A2 speaks against the existence of severe aortic stenosis
  • Paradoxical splitting of the S2: Resulting from late closure of the aortic valve with delayed A2
  • Accentuated P2: In the presence of secondary pulmonary hypertension
  • Ejection click: Common in children and young adults with congenital aortic stenosis and mobile valve leaflets
  • Prominent S4: Resulting from forceful atrial contraction into a hypertrophied left ventricle
  • Systolic murmur: The classic crescendo-decrescendo systolic murmur of aortic stenosis begins shortly after the first heart sound; the intensity increases toward mid systole and then decreases, with the murmur ending just before the second heart sound.



 Peritonitis is defined as an inflammation of the serosal membrane that lines the abdominal cavity and the organs contained therein. Depending on the underlying pathology, the resultant peritonitis may be infectious or sterile (ie, chemical or mechanical).

Peritoneal infections are classified as primary (ie, from hematogenous dissemination, usually in the setting of an immunocompromised state), secondary (ie, related to a pathologic process in a visceral organ, such as perforation or trauma, including iatrogenic trauma), or tertiary (ie, persistent or recurrent infection after adequate initial therapy). Primary peritonitis is most often spontaneous bacterial peritonitis (SBP) seen mostly in with chronic liver disease. Secondary peritonitis is by far the most common form of peritonitis encountered in clinical practice. Tertiary peritonitis often develops in the absence of the original visceral organ pathology.

Infections of the peritoneum are further divided into generalized (peritonitis) and localized (intra-abdominal abscess).


Hypomagnesemia is common among hospitalized patients and frequently occurs with other electrolyte disorders, including hypokalemia and hypocalcemia. Magnesium depletion usually results from inadequate intake plus impairment of renal conservation or gastrointestinal absorption.

Drugs can cause hypomagnesemia. Examples include chronic (> 1 year) use of a proton pump inhibitor and concomitant use of diuretics. Amphotericin B can cause hypomagnesemia, hypokalemia, and acute kidney injury. The risk of each of these is increased with duration of therapy with amphotericin B and concomitant use of another nephrotoxic agent. Liposomal amphotericin B is less likely to cause either kidney injury or hypomagnesemia.

Trousseau sign is the precipitation of carpal spasm by reduction of the blood supply to the hand with a tourniquet or blood pressure cuff inflated to 20 mm Hg above systolic blood pressure applied to the forearm for 3 minutes.

Chvostek sign is an involuntary twitching of the facial muscles elicited by a light tapping of the facial nerve just anterior to the exterior auditory meatus.

Serum magnesium concentration < 1.8 mg/dL

Hypomagnesemia is diagnosed by measurement of serum magnesium concentration.

Severe hypomagnesemia usually results in concentrations of < 1.25 mg/dL.

Associated hypocalcemia and hypocalciuria are common.

Hypokalemia with increased urinary potassium excretion and metabolic alkalosis may be present.

Treatment with magnesium salts is indicated when magnesium deficiency is symptomatic or the magnesium concentration is persistently < 1.25 mg/dL. Patients with alcohol use disorder are treated empirically. In such patients, deficits approaching 12 to 24 mg/kg are possible.

When serum magnesium is ≤ 1.25 mg/dL but symptoms are less severe, magnesium sulfate may be given IV in 5% D/W at a rate of 1 g/hour as slow infusion for up to 10 hours. In less severe cases of hypomagnesemia, gradual repletion may be achieved by administration of smaller parenteral doses over 3 to 5 days until the serum magnesium concentration is normal. 

 

Procalcitonin (PCT) has developed into a promising new biomarker for early detection of (systemic) bacterial infections. PCT is a 116-amino acid residue that was first explained by Le Moullec et al. in 1984; however, its diagnostic significance was not recognized until 1993. In 1993, Assicot et al. demonstrated a positive correlation between high serum levels of PCT and patients with positive findings for bacterial infection and sepsis (eg, positive blood cultures). PCT assays with a specificity of 79%, is utilized to more accurately determine if a bacterial species is the cause of a patient’s systemic inflammatory reaction.

Procalcitonin serum levels have been shown to increase 6 to 12 hours following initial bacterial infections and increase steadily 2 to 4 hours following the onset of sepsis. The half-life of PCT is between 20 to 24 hours; therefore, when a proper host immune response and antibiotic therapy are in place, PCT levels decrease accordingly by 50% over 24 hours.

PCT serum levels can become elevated among patients during times of noninfectious conditions, such as with trauma, burns, carcinomas (medullary C-cell, small cell lung, & bronchial carcinoid), immunomodulator therapy that increase proinflammatory cytokines, cardiogenic shock, first 2 days of a neonate's life, during peritoneal dialysis treatment, and in cirrhotic patients (Child-Pugh Class C). Furthermore, PCT levels have found to be falsely elevated in patients suffering from various degrees of chronic kidney disease which can, in turn, alter baseline results making the determination of an underlying bacterial infection difficult to establish.



 Thoracolumbar Spine Fracture

The most common mechanisms for thoracolumbar traumatic injuries include motor vehicle accidents, falls from height, recreational injuries, and work-related injuries. Most of them are high-velocity and high-energy injuries, which usually involve additional injuries.

The T10-L2 thoracolumbar region is the most common area of injury to the spine from trauma due to the specific biomechanics of this segment of the spine. Injury to this area can result in a permanent neurological deficit from compression or direct injury to the nerve roots of the cauda equina or the conus medullaris and warrants immediate attention and assessment.

American Spinal Injury Association (ASIA) impairment scale:

A - Complete: No motor or sensory function is preserved below the neurological level

B - Incomplete: Sensory function preserved but no motor function is preserved below the neurological level including the S4–S5 segments

C - Incomplete: Motor function is preserved at the most caudal sacral segments for voluntary anal contraction. The motor function below the neurological level is preserved with less than half of key muscles that have a muscle grade ≥ 3

D - Incomplete: Motor function is preserved below the neurological level with at least half of key muscles that have a muscle grade ≥ 3

E - Normal: Motor and sensory function are normal

Compression fracture. While the front (anterior) of the vertebra breaks and loses height, the back (posterior) part of it does not. This type of fracture is usually stable (the bones have not moved out of place) and is rarely associated with neurologic problems. Compression fractures commonly occur in patients with osteoporosis.

Axial burst fracture.  In this type of fracture, the vertebra loses height on both the front and back sides. It is often caused by landing on the feet after falling from a significant height. An axial burst fracture can sometimes result in nerve compression. Some fractures are stable, while others are significantly unstable (the bones have moved out of place).

Hematology Algorithms 

Anemia is described as a reduction in the proportion of the red blood cells. Most patients experience some symptoms related to anemia when the hemoglobin drops below 7.0 g/dL. RBC are produced in the bone marrow and released into circulation. Approximately 1% of RBC are removed from circulation per day. Imbalance in production to removal or destruction of RBC leads to anemia. 

The etiology of anemia depends on whether the anemia is hypo-proliferative (i.e., corrected reticulocyte count <2%) or hyperproliferative (i.e., corrected reticulocyte count >2%).  Hypo-proliferative anemias are further divided by the mean corpuscular volume into microcytic anemia (MCV<80 fl), normocytic anemia (MCV 80-100 fl) & macrocytic anemia (MCV>100 fl). 

Pancytopenia is a hematologic condition characterized by a decrease in all three peripheral blood cell lines. It is characterized by the hemoglobin of less than 12 g/dL in women and 13 g/dL in men, platelets of less than 150,000 per mcL, and leukocytes of less than 4000 per ml (or absolute neutrophil count of less than 1800 per ml). However, these thresholds largely dependent on age, sex, race as well as varying clinical scenarios. 

Leukopenia is primarily seen as neutropenia since neutrophils constitute the majority of the leukocytes. The etiology of pancytopenia can be broadly categorized as a central type that involves production disorders or a peripheral type that involves disorders of increased destruction. These causes could contribute to the pancytopenia independently or as a combination. 

Red cell distribution width (RDW) = (standard deviation of MCV/mean MCV) × 100. 

Normal range11.5–14.5% has suspicion of thalassemia trait & high often indicates IDA 

Mentzer index = (MCV/RBC count). 

< 13 may represent thalassemia trait & >13 often indicates IDA



 Normal coagulation pathway represents a balance between the pro coagulant pathway that is responsible for clot formation and the mechanisms that inhibit the same beyond the injury site. Imbalance of the coagulation system may occur in the perioperative period or during critical illness, which may be secondary to numerous factors leading to a tendency of either thrombosis or bleeding.

The plasma coagulation system in mammalian blood consists of a cascade of enzyme activation events in which serine proteases activate the proteins (proenzymes and procofactors) in the next step of the cascade via limited proteolysis. The ultimate outcome is the polymerization of fibrin and the activation of platelets, leading to a blood clot. This process is protective, as it prevents excessive blood loss following injury (normal hemostasis). Unfortunately, the blood clotting system can also lead to unwanted blood clots inside blood vessels (pathologic thrombosis), which is a leading cause of disability and death in the developed world. There are two main mechanisms for triggering the blood clotting, termed the tissue factor pathway and the contact pathway. Only one of these pathways (the tissue factor pathway) functions in normal hemostasis. Both pathways, however, contribute to thrombosis. 

The blood coagulation cascade culminates with the conversion of fibrinogen to fibrin, essentially transmitting the proteolytic injury signal into a fibrin clot capable of occluding the inciting tissue defect. Fibrinogen is the most abundant coagulation protein in plasma, consistent with its mechanical rather than signaling role.


 A gut diverticulum (singular) is an outpouching of the wall of the gut to form a sac. Diverticula (plural) may occur at any level from esophagus to colon. A true diverticulum includes all three layers of the gut; the lining mucosa, the muscularis, and the outer serosa. False diverticula are missing the muscularis and are therefore very thin walled. Colonic diverticula are typically false.


 There are 3 types of artificial pacemakers:

  • Implantable pulse generators with endocardial or myocardial electrodes
  • External, miniaturized, patient portable, battery-powered, pulse generators with exteriorized electrodes for temporary transvenous endocardial or transthoracic myocardial pacing
  • Console battery or AC-powered cardioverters or monitors with high-current external transcutaneous or low-current endocardial or myocardial circuits for temporary pacing in asynchronous or demand modes, with manual or triggered initiation of pacing

Following conditions are included in the ACC/AHA/HRS guidelines for the pacemaker insertion

  • Sinus Node Dysfunction

  1. Documented symptomatic sinus bradycardia including frequent sinus pauses which produce symptoms and symptomatic sinus bradycardia that results from required drug therapy for medical condition
  2. Symptomatic chronotropic incompetence (failure to achieve 85% of age-predicted maximal heart rate during formal or informal stress test or inability to mount age appropriate heart rate during activities of daily living)

  • Acquired Atrioventricular (AV) Block

  1. Complete third-degree AV block with or without symptoms.
  2. Symptomatic second degree AV block, Mobitz type I and II
  3. Exercise-induced second or third degree AV block in the absence of myocardial infarction
  4. Mobitz II with widened QRS complex

  • Chronic Bifascicular Block

  1. Advanced second-degree AV block or intermittent third-degree AV block
  2. Alternating bundle-branch block
  3. Type II second-degree AV block.

  • After Acute Phase of Myocardial Infarction

  1. Permanent ventricular pacing for persistent second degree AV block in the His-Purkinje system with alternating bundle branch block or third degree AV block within or below the His-Purkinje system after the ST-segment elevation MI (STEMI)
  2. Permanent ventricular pacing for a transient advanced second or third-degree infranodal AV block and associated bundle branch block
  3. Permanent ventricular pacing for persistent and symptomatic second or third degree AV block

  • Neurocardiogenic Syncope and Hypersensitive Carotid Sinus Syndrome

  1. Recurrent syncope caused by spontaneously occurring carotid sinus stimulation and carotid sinus pressure that induces ventricular asystole of more than 3 seconds

  • Post Cardiac Transplantation

  1. For persistent inappropriate or symptomatic bradycardia not expected to resolve and for other class I indications of permanent pacing.

  • Hypertrophic Cardiomyopathy (HCM)

  1. Patients with HCM having Sinus node dysfunction and AV block

  • Pacing to Prevent Tachycardia

  1. For sustained pause dependent VT, with or without QT prolongation

  • Cardiac Resynchronization Therapy (CRT) in Patients with Severe Systolic Heart Failure

  1. Patients with left ventricular ejection fraction (LVEF) of less than or equal to 35%, sinus rhythm, LBBB (left bundle branch block), New York Heart Association (NYHA) Class II, III or IV symptoms while on optimal medical therapy with a QRS duration of greater than or equal to 150 ms, CRT with or without ICD is indicated

  • Congenital Heart Disease

  1. For advanced second or third-degree AV block associated with symptomatic bradycardia, ventricular dysfunction, or low cardiac output; also for advanced second or third-degree AV block which is not expected to resolve or persists for 7 days or longer after cardiac surgery
  2. For sinus node dysfunction with a correlation of symptoms during age inappropriate bradycardia
  3. Congenital third-degree AV block with a wide QRS escape rhythm, complex ventricular ectopy or ventricular dysfunction
  4. Congenital third-degree AV block in an infant with a ventricular rate of less than or equal to 55 bpm or with congenital heart disease with a ventricular rate of less than or equal to 70 bpm


 Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a new class of glucose-lowering drugs. They work by blocking the low-affinity, high-capacity SGLT2 protein located in the proximal convoluted tubule of the nephron. The SGLT2 protein is responsible for the resorption of approximately 90% of filtered glucose while the remainder is reabsorbed by SGLT1 proteins found on the distal part of the proximal convoluted tubule. SGLT2 inhibition results in glycosuria (and natriuresis as the protein is a co-transporter), thereby lowering plasma glucose concentrations. This mechanism is unique compared with all other glucose-lowering agents as it does not interfere with endogenous insulin or incretin pathways.

In recent cardiovascular outcome trials, SGLT2 inhibitors are associated with 30%–35% lower risk of hospitalization for heart failure. Other glucose-lowering agents appear to be more potent than SGLT2 inhibitors, but fail to reduce cardiovascular risk, particularly with regard to heart failure outcomes. Moreover, although the glucose-lowering efficacy of SGLT2-inhibitor therapy declines at lower estimated glomerular filtration rates, its cardiovascular benefits are remarkably preserved, even in patients with renal impairment. This implies differing mechanisms of action in glycemic control and cardiovascular risk reduction. 



 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).


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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