Synthesis and metabolism of vitamin D in the regulation of calcium, phosphorus, and bone metabolism.

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During exposure to solar UVB radiation, 7-dehydrocholesterol in the skin is converted to previtamin D3, which is immediately converted to vitamin D3 in a heat-dependent process. Excessive exposure to sunlight degrades previtamin D3 and vitamin D3 into inactive photoproducts. Vitamin D2 and vitamin D3 from dietary sources are incorporated into chylomicrons and transported by the lymphatic system into the venous circulation. Vitamin D (hereafter, “D” represents D2 or D3) made in the skin or ingested in the diet can be stored in and then released from fat cells.
Vitamin D in the circulation is bound to the vitamin D–binding protein, which transports it to the liver, where vitamin D is converted by vitamin D-25-hydroxylase to 25(OH)D. This is the major circulating form of vitamin D that is used by clinicians to determine vitamin D status. (Although most laboratories report the normal range to be 20 to 100 ng/mL [50 to 250 nmol/L], the preferred range is 30 to 60 ng/mL [75 to 150 nmol/L].) This form of vitamin D is biologically inactive and must be converted in the kidneys by 25-hydroxyvitamin D-1α-hydroxylase (1-OHase) to the biologically active form 1,25(OH)2D.
 Serum phosphorus, calcium, fibroblast growth factor 23 (FGF-23), and other factors can either increase (+) or decrease (−) the renal production of 1,25(OH)2D. 1,25(OH)2D decreases its own synthesis through negative feedback and decreases the synthesis and secretion of PTH by the parathyroid glands. 1,25(OH)2D increases the expression of 25-hydroxyvitamin D-24-hydroxylase (24-OHase) to catabolize 1,25(OH)2D to the water-solubl biologically inactive calcitroic acid, which is excreted in the bile.

1,25(OH)2D enhances intestinal calcium absorption in the small intestine by interacting with the vitamin D receptor–retinoic acid x-receptor complex (VDR-RXR) to enhance the expression of the epithelial calcium channel (transient receptor potential cation channel, subfamily V, member 6 [TRPV6]) and calbindin 9K, a calcium-binding protein (CaBP). 1,25(OH)2D is recognized by its receptor in osteoblasts, causing an increase in the expression of the receptor activator of RANKL.
RANK, the receptor for RANKL on preosteoclasts, binds RANKL, which induces preosteoclasts to become mature osteoclasts. Mature osteoclasts remove calcium and phosphorus from the bone, maintaining calcium and phosphorus levels in the blood. Adequate Ca2+ and phosphorus (HPO42−) levels promote the mineralization of the skeleton.

Skin manifestations of Pellagra

Pellagra is a a vitamin deficiency disease caused by chronic lack of nicotinic acid (niacin, vitamin B3) or its precursor, tryptophan.Niacin is required for most cellular processes.

CAUSE of Pellagra:

Inadequate niacin and/or tryptophan in the diet mainly seen in developing countries or poverty stricken areas "called Primary pellagra".But usually there is something prevents Niacin absorption and processing and causes secondary pellagra such as:
• Alcoholism, malabsorption, anorexia nervosa, Prolonged diarrhoea, Liver cirrhosis, Drugs e.g. isoniazid, azathioprine

• Carcinoid tumors (excessive use of tryptophan, which produces serotonin)

Symptoms and signs of Pellagra is classically described by "the four D's": diarrhea, dermatitis, dementia and If left untreated, death.

Skin manifestations and clinical finding of Pellagra:

-At first there is reddened skin with superficial scaling in areas exposed to sunlight, heat & friction. This may resemble severe sunburn then gradually subsides leaving a dusky brown-red colouration .
-The rash is usually symmetrical with a clear edge between affected and unaffected skin and sometimes may be itching or burning sensation
-Other features sometimes present include cheilosis, glossitis, angular stomatitis, and oral or perianal sores.

Legs and feet of a patient with niacin deficiency. A, Before therapy. B, After therapy.

(From Swartz MH: Textbook of Physical Diagnosis, 5th ed. Philadelphia, WB Saunders, 2006.)

TREATMENT of Pellagra:

• Nutritional supplementation with niacin will improve the appearance of skin lesions

Algorithm of the cause of Hypokalaemia

A history of vomiting, diarrhoea, or use of medications such as diuretics can be helpful in determining the cause of hypokalaemia. However, in some cases, the cause of hypokalaemia is not readily apparent. In these cases, measurements of BP and urinary potassium excretion, and assessment of acid-base balance are often helpful.

Serum potassium concentrations:
There is no strict correlation between the serum potassium concentration and total body potassium stores. In chronic hypokalaemia, a potassium deficit of 200 to 400 mmol (200 to 400 mEq) is required to lower the serum potassium concentration by 1 mmol/L (1 mEq/L). These estimates are good provided there is no concurrent acid-base abnormality (e.g., for diabetic ketoacidosis or severe non-ketotic hyperglycaemia).

In diabetic ketoacidosis patients may have a normal or even elevated serum potassium concentration at presentation, despite having a marked potassium deficit due to urinary and GI losses.

Spurious hypokalaemia can occur when blood with a high WBC count is left at room temperature due to extraction of potassium by the WBCs. It is therefore important to consider repeating the test for confirmation.

Synthesis of eicosanoid autacoids

The eicosanoids are an important group of endogenous fatty acid derivatives that are produced from arachidonic acid, a 20-carbon fatty acid lipid in cell membranes. Major families of eicosanoids include the straight-chain derivatives (leukotrienes) and cyclic derivatives (prostacyclin, prostaglandins, and thromboxane). Inhibitors of the eicosanoids are shown in Figure below.

ABCD causes of BUN:creatinine elevation

BUN stands for blood urea nitrogen which measures the amount of urea nitrogen, a waste product of protein metabolism, in the blood. Urea is formed by the liver and carried by the blood to the kidneys for excretion. Because urea is cleared from the bloodstream by the kidneys, a test measuring how much urea nitrogen remains in the blood can be used as a test of renal function. However, there are many factors besides renal disease that can cause BUN alterations, including protein breakdown, hydration status, and liver failure.


values for BUN:
* Adult: 7-20 mg/100 ml; men may have slightly higher values than women
* Pregnancy: values decrease about 25%
* Newborn: values slightly lower than adult ranges
* Elderly: values may be slightly increased due to lack of renal concentration

##BUN:creatinine elevation: causes ABCD:

• Azotremia (pre-renal)


• Bleeding (GI)


• Catabolic status


• Diet (high protein parenteral nutrition)

Scheme for Metabolic acidosis

Metabolic acidosis is a commonly presenting feature and is often caused by diabetes, renal failure or poisoning. However, it can cause diagnostic difficulties, particularly in the acute situation when patients can be seriously ill and where the aetiology is not obvious. It is vital that its diagnosis is considered in the clinical context with attention given to history (especially of drugs) and physical signs.

Metabolic acidosis is characterised by a raised [H+] and a low / normal PCO2 (in contrast with respiratory acidosis where the PCO2 is high). A low derived bicarbonate or low plasma total CO2 accompanies the raised [H+].

The raised [H+] stimulates the respiratory centre and hyperventilation occurs with a consequent rise in PO2. Hyperventilation reduces PCO2 and hence some of the potential acid burden on the body and acts to compensate for the metabolic acidosis. Complete compensation does not occur (ie the [H+] remains elevated) and the extent of the compensation will be limited in patients with an underlying diminution in respiratory function.

Some confusion may occur in patients admitted with 'collapse' and in extremis. Cardio respiratory collapse will result in a mixed acidosis due to a peripheral metabolic acidosis due to poor perfusion and a respiratory acidosis due to poor ventilation resulting in a raised [H+] and raised PCO2.

Iron Deficiency Anemia: Causes and Treatment

Mechanisms Linked to Sodium intake in Hypertension

Mechanisms Linked to Increases in Blood Pressure and the Therapeutic Effects of Healthful Dietary Patterns, Sodium Reduction, and Weight Loss.

Sodium intake initiates an autoregulatory sequence that leads to increased intravascular fluid volume and cardiac output, peripheral resistance, and blood pressure. The elevation in blood pressure results in a phenomenon called pressure natriuresis, in which increased renal perfusion pressure leads to increased excretion of fluid and sodium. In essential hypertension, however, sodium excretion is impaired. It is hypothesized that in most cases essential hypertension is a genetic disorder involving many individual genes, each of which influences the body's handling of sodium to varying degrees and becomes expressed in the context of an unhealthful dietary environment, particularly one characterized by excessive intake of salt.

Hyperlipidemia: Cholesterol Guidelines

Dr. Melissa Stiles interviews Dr. Patrick McBride about the NCEP Adult Treatment Panel III Cholesterol Guidelines.
Part 1


Part 2

Clinical Approach to Metabolic Alkalosis

History

Obtain historical data to pinpoint the nature of the disease causing metabolic alkalosis.

* Ask the patient about history of vomiting, other gastric fluid loss, and diuretic use. Loss of gastric fluid and HCl due to vomiting is the most common cause of metabolic alkalosis.

• Vomiting may be caused by pyloric stenosis or ulcers. Occasionally, it may be self-induced.
• Significant gastric fluid loss can occur via long-term nasogastric (NG) tube drainage.
• Diuretic use may lead to increased chloride losses.

* Obtain information about specific disease states such as primary hyperaldosteronism, reninism, hyperglucocorticoidism, Bartter syndrome, and deoxycorticosterone (DOC) excess syndromes.
* Because hypokalemia may lead to metabolic alkalosis, ask about the use of diuretics because these lead to potassium loss.

An algorithm for metabolic alkalosis

Physical

Increased neuromuscular excitability sometimes causes tetany or seizures. Generalized weakness may be noted if the patient also has hypokalemia. Signs and symptoms observed with metabolic alkalosis usually relate to the specific disease process that caused the acid-base disorder.

* Patients who develop metabolic alkalosis from vomiting can have symptoms related to severe volume contraction, with signs of dehydration that include tachycardia, dry mucous membranes, decreased skin turgor, postural hypotension, poor peripheral perfusion, and weight loss.
* Although diarrhea typically produces a hyperchloremic metabolic acidosis, diarrheal stools may rarely contain significant amounts of chloride, as in the case of congenital chloride diarrhea. Children with this condition present at birth with watery diarrhea, metabolic alkalosis, and hypovolemia.
* Weight gain and hypertension may accompany metabolic alkalosis that results from a hypermineralocorticoid state.