Biliary system and physiology

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.

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Mercedes Benz sign

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

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Warfarin induced skin necrosis

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.

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Exophthalmos

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.

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Bladder outlet obstruction (BOO)

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.

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Clinical Hematology

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.

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Hip fracture

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.

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Circle of Willis

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.

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Hemochromatosis

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.

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Brain natriuretic peptide

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.

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Pseudomonas aeruginosa and antibiotics.

 Pseudomonas aeruginosa and antibiotics.

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Malnutrition

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).

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