What causes clubbing?

Nail clubbing is one of the first things we look for when examining patients, but just like C-reactive protein in a blood test, it is a non specific sign of disease that often won’t help narrow your differential. To name just a few, it is associated with forms of heart, lung, gastrointestinal, and thyroid disease. But what causes clubbing? The most widely accepted theory is the ‘Platelet Theory’.

Megakaryocytes are large bone marrow derived cells released into the circulation that give rise to platelets but also a series of growth factors. A significant proportion of megakaryocytes reside in the lungs but during inflammation, megakaryocytes migrate from the lungs to the peripheries and become trapped in nail bed capillaries where they deposit their growth factors such as PDGF and VEGF. This leads to connective tissue proliferation and the characteristic thickening of the distal phalanx, increased nail curvature, and reduction of the angle between the nail and the cuticle.

What about non inflammatory disease? In congenital heart disease, a right to left shunt will cause megakaryocytes to bypass the pulmonary circulation into the systemic circulation where they will also be trapped in capillaries in the nail beds.


Why are some rashes non-blanching?

To blanch or not to blanch, that is the question.

Blood extravasation into dermal layers –> Purpura –> Non-blanching

Purpura describes the red-purple lesions caused by extravasation of blood into the skin or mucous membranes. These can be small (petechiae <3mm) or larger (ecchymoses). These are caused by infection (meningococcal septicaemia), coagulopathies, and the vasculitidies (the purpura will be palpable).

As the blood products are in the epidermal layers, applied pressure (i.e. the glass test) does not reduce the red discolouration of the skin.

Inflammatory vasodilation of blood vessels –> Erythema –> Blanching

Conversely, erythematous rashes are caused by localised vasodilation and thus, blood products are retained in the vasculature. When pressure is applied, blood in these vessels is squeezed away from the site and so the skin blanches.

Why does systolic blood pressure drop with inspiration?

Breathe in.

As you do, the expansion of your chest reduces the pressure in the thorax below atmospheric pressure.

This has two effects on the heart:

  1. Reduced pressure on the Vena Cava, means more venous return to the right side of the heart
  2. Increased capacity of the pulmonary arteries (as they are pulled open), reduced venous return to the left side of the heart

This imbalance of heart filling compromises left ventricular capacity. The resultant reduction in stroke volume causes a reduction in systolic blood pressure by <10mmHg.


Cardiac Output = Stroke Volume x Heart Rate

Cardiac output is maintained by a baroreceptor-mediated increase in sympathetic outflow to the heart resulting in an increased pulse rate.

Breathe out.

What is Stridor?

Stridor is a coarse, high pitched sound generated by anatomical abnormalities or obstruction of the upper airway. It is not a disease in itself. It can be inspiratory (most common), expiratory, or biphasic. Inspiratory stridor arises from obstruction of the extra-thoracic airway (larynx, pharynx, upper trachea). Expiratory stridor arises from obstruction of the intrathoracic airway (lower trachea and and bronchi). Biphasic stridor implies glottic involvement.

Inspiratory stridor is more common in children as they have relatively narrowed and flexible airways that are more predisposed to collapse. If we consider a gas at rest, it will exert pressure in all directions equally. However, during inspiration, air is drawn into the airways and the force the gas exerts in the direction it is moving parallel to the airways is greater than the pressure exerted on the walls of the airway. As this latter pressure falls, the airway can collapse and be obstructed, causing stridor. Because children’s airways are narrower, there are also more likely to develop stridor secondary to upper airway obstruction from inflammation, oedema, or foreign bodies.

Expiratory stridor is more complicated. Upon inspiration, the expansion of the chest and resultant negative intrathoracic pressure causes the intrathoracic portion of the trachea to be drawn open. Conversely, the extrathoracic, upper portion of the trachea experiences an external positive pressure and its diameter reduces. Conversely, during expiration, the extrathoracic trachea increases in diameter and the intrathoracic trachea narrows as the intrathoracic pressure increases. In a healthy individual, the trachea remains sufficiently patent during inspiration and expiration such that stridor does not occur. However, when the intrathoracic trachea narrows beyond normal limits, especially in the presence of secretions or oedema, the airway obstructs and stridor will be heard on expiration rather than inspiration.

Dr. Know welcomes you…

This is what medical students and doctors have been waiting for. Dr Know will provide no frills explanations to the science underlying clinical signs and the answers to questions you think you know the answers to, but probably don’t.

Did you know that…

Clubbing is caused by megakaryocyte deposition in the nailbeds?

You can’t be cyanosed if you’re anaemic?

A wheeze is not always just expiratory and stridor is not always inspiratory?

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