Role of Calcium in Cardiovascular Function
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
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
THREE HORMONE AND THREE ORGAN
• ACTIVATED VITAMIN D
• 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
; 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.
• 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
; Mineralization of osteoid occurs spontaneously when adequate amounts of
calcium and phosphorous are available
• 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 and Excitation Contraction Coupling in Cardiac
• 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
• 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
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
• 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-
• a normal ionized calcium of 1.1-1.4 mmol/L (4.5-5.6 mg/dL).
• Low levels of serum calcium
• Common conditions associated with Hypocalcemia are: • Hypoparathyroidism
• 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
• Cardiac arrhythmias
– ECG changes include:
– Prolonged QTc interval
– Prolonged ST interval
• An elevated calcium level in the blood
• Vitamin-D intoxication
• Milk alkali syndrome
• Disorders related to high bone-turnover rates • Sign and Symptoms of Hypercalcemia • include fatigue
• 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