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Role of Calcium in Cardiovascular Function

By Connie Lawrence,2014-11-26 12:28
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Role of Calcium in Cardiovascular Function

    Role of Calcium in Cardiovascular Function

    Learning Objectives

    By the end of this lecture the students should be able to understand: Calcium metabolism

     Calcium regulation

     The role of calcium in cardiac muscle contraction

     Calcium, excitation contraction coupling and T-tubules in cardiac muscle The role of Calcium in vascular smooth muscle

     Calcium channel blockers

     Normal ranges of extracellular calcium Hypocalcemia

     Hypercalcemia

    Role of Calcium

     An essential intracellular and extracellular cation

     Extracellular calcium is required to maintain normal biological function of nervous system, the

    musculoskeletal system, and blood coagulation

     Intracellular calcium is needed for normal activity of many enzymes;

     Preservation of the integrity of cellular membrane

     Regulation of endocrine and exocrine secretary activities

     Activation of compliment system

     Bone metabolism

    Calcium Metabolism Calcium metabolism or calcium homeostasis is the mechanism by which the body maintains

    adequate calcium levels.

     Derangements of this mechanism lead to hypercalcemia or hypocalcemia, both of which can

    have important consequences for health.

     Total Body Calcium

     99% of the bodies calcium is in the bone in calcium phosphate compounds

     1% of total body calcium is intracellular

     0.1% of total body calcium is in extracellular fluid

Calcium in Plasma

     In ECF:

     Unionized Calcium=50%

     41% is bound to plasma proteins

     9% is bound to anions like citrate and phosphate Ionized calcium=50%

     It is the ionized form of Calcium which is free and is of functional significance

    Calcium Homeostasis

    THREE HORMONE AND THREE ORGAN

     PTH

     ACTIVATED VITAMIN D

     CALCITONIN

     BONE

     KIDNEY

     SMALL INTESTINE

    Parathyroid Hormone (PTH)

     If blood levels of ionized calcium drop by as little as 0.1 mg/dl, secretion of PTH is stimulated ; PTH acts directly on distal portion of the nephron to decrease urinary excretion of calcium

    mediated by cAMP.

    ; PTH powerfully inhibits tubular reabsorption of phosphate and thus increases urinary phosphate

    excretion

    ; PTH stimulates the renal enzyme that converts vit D to its active form but has no direct effects

    on intestinal transport of calcium or phosphate.

    Vitamin D

     Activated Vit D: 1,25(OH)2 Cholecalceferol

     GI - increase Ca absorption.

     Bone - increase Ca mobilization.

     Kidney - increase reabsorption within the distal tubule

    ; Deficiency of vitamin D severely impairs intestinal transport of both calcium and

    phosphorous

    ; Mineralization of osteoid occurs spontaneously when adequate amounts of

    calcium and phosphorous are available

    Calcitonin

     Secreted from Parafollicular cells of the Thyroid gland in response of hypercalcemia Aims to decrease extracellular calcium conc.

     Decrease osteoclast activity

     Stimulates a distal tubular mediated calciuresis.

    Calcium Regulation

    Calcium and Excitation Contraction Coupling in Cardiac

    Muscle

     Excitation contraction coupling occurs when the action potential from the Sinoatrial Node

    induces a cardiomyocyte to contract.

     Upon depolarization calcium ions enter a cell through L-type calcium channels of the

    sarcolemma.

     This release of calcium triggers a subsequent release of calcium from the sarcoplasmic reticulum In addition to calcium released from SR, a large quantity of extracellular calcium diffeses into the

    SR from the T tubules

     Thus, the strength of Cardic mucscle contraction depends to a great extent on extracellular

    calcium conc.

    Excitation Contraction Coupling

    Calcium in Vascular Smooth Muscle Intracellular calcium concentrations regulates smooth muscle contraction An increase in free intracellular calcium can result from by opening voltage dependent calcium

    channels (L-type calcium channels)

     The free calcium binds to calmodulin.

     Calcium-calmodulin activates myosin light chain kinase (MLCK)

     MLC phosphorylation leads to cross-bridge formation between the myosin heads and the actin

    filaments, and hence, smooth muscle contraction.

    Calcium Channel Blockers

    2+ By blocking L-type channels in arterial smooth muscle they reduce Ca influx during

    depolarisation

     CCBs act on resistance vessels and are potent arterial vasodilators. They: Reduce peripheral vascular resistance

     Lower arterial blood pressure

     Antagonize vasospasms in coronary or peripheral arteries

     By reducing afterload CCBs also reduce cardiac oxygen demand Acting on heart, exert negative inotropic, dromotropic and chronotropic actions Are licensed for the treatment of angina, vasospastic angina and hypertension.

    Abnormalities in Serum Calcium The serum level of calcium is closely regulated with a normal total calcium of 2.2-2.6 mmol/L (9-

    10.5 mg/dL)

     a normal ionized calcium of 1.1-1.4 mmol/L (4.5-5.6 mg/dL).

    Pathology:

     Hypocalcemia

Hypercalcemia

    Hypocalcemia

     Low levels of serum calcium

     Common conditions associated with Hypocalcemia are: Hypoparathyroidism

     Parathyroidectomy

     DiGeorge Syndrome

     Chronic renal failure

     vitamin D deficiency

    Sign and Symptoms of Hypocalcemia

     Perioral tingling and paraesthesia

     Tetany and carpopedal spasm

     Trousseau sign of latent tetany (eliciting carpal spasm by inflating the blood pressure cuff and

    maintaining the cuff pressure above systolic Chvostek's sign (tapping of the inferior portion of the zygoma will produce facial spasms)

     Tendon reflexes are hyperactive

     Laryngospasm

     Cardiac arrhythmias

     ECG changes include:

     Prolonged QTc interval

     Prolonged ST interval

    Hypercalcemia

     An elevated calcium level in the blood

     Causes:

Hyperparathyroidism

     Malignancy

     Vitamin-D intoxication

     Milk alkali syndrome

     Disorders related to high bone-turnover rates Sign and Symptoms of Hypercalcemia include fatigue

     Anorexia

     Nausea

     Vomiting

     Pancreatitis

     Increased urination

    Abnormal heart rhythms can result, and ECG findings of a short QT interval and a widened T wave

    ECG Changes in Hypocalcemia

Hypercalcemia: The QT interval is short

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