Physiology
Cardiovascular
Digoxin exhibits its positive inotropic effect by which of the following mechanisms:
Answer:
Cardiac glycosides (e.g. digoxin) slow the removal of Ca2+ from the cell by inhibiting the membrane Na+ pump (Na+/K+ ATPase) which generates the Na+ gradient required for driving the export of Ca2+ by Na+/Ca2+ exchange; consequently the removal of Ca2+ from the myocyte is slowed and more Ca2+ is available for the next contraction.Inotropic Effects on Heart
Physiology / Cardiovascular / Cardiac Cycle
Last Updated: 28th February 2019
Factors that affect intracellular [Ca2+] and hence cardiac contractility are called inotropes.
Sympathetic stimulation increases cardiac muscle contractility because it causes release of noradrenaline. Noradrenaline is a positive inotrope; it binds to β1-adrenoceptors on the membrane and causes increased Ca2+ entry via L-type channels during the AP and thus increases Ca2+ release from the SR. Noradrenaline also increases Ca2+ sequestration into the SR and thus more Ca2+ is available for the next contraction.
Cardiac glycosides (e.g. digoxin) slow the removal of Ca2+ from the cell by inhibiting the membrane Na+ pump which generates the Na+ gradient required for driving the export of Ca2+; consequently the removal of Ca2+ from the myocyte is slowed and more Ca2+ is available inside the myocyte for the next contraction.
Acidosis is negatively inotropic, largely because H+ competes for Ca2+ binding sites.
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
