Place of the Nail Fold in Human Microvascular Studies

Why the Nail Fold?

Most human studies of microvasculature have used the technique of in vivo microscopy, taking advantage of the fact that superficial microvessels of the skin can be visualized by rendering the skin surface smooth by application of oil. This noninvasive method, discovered in the beginning of the 20th century, appealed to many investigators. O. Müller in 1922 published his extensive observations from a great number of areas of human skin, in both health and disease, illustrated by careful drawings that demonstrate the considerable variability of skin microvasculature from site to site.

Over time, however, NF became the favorite site because it was easy to place a finger under the microscope, and serial studies were facilitated, because the exact location of initial observations could be easily identified.

The pattern of NF capillaries varies with age. In a normal newborn baby only a plexus of microvessels can be seen;



Microscope Microvessels
Figure 1 Sagittal section of a finger nail fold in a normal healthy subject.
Figure 2 The wide-field view of the nail fold in a scleroderma patient and a normal control. (Left) Characteristic scleroderma-type capillary loops of various sizes and moderate to extensive loss of capillaries. (Right) Capillary distribution in the NF of a normal subject.

there are no papillary capillaries. Gradually over the first months of life a papillary layer of microvessels appears. Their density is less than in an adult and the subpapillary plexus can still frequently be seen. It appears as a polygonal network, different from the subpapillary venual plexus seen in later life. The latter appears to be a genetic trait, transmitted as Mendelian dominant, but may also be related to disease or to drugs used for treatment. In aged subjects, a decreased density of NF capillaries can occur, often associated with disease rather than aging per se.

The endrow capillaries (those in the terminal row) tend to have larger diameters than more proximally located capil laries. Because of their horizontal position, they can be seen to a greater length. Thus, it is possible to perform measurements of capillary diameters, observe red blood cell (RBC) flow, and also use minimally invasive procedures, such as capillary pressure recordings in this location.

If not otherwise indicated, NF refers to the NF of the finger, where the majority of the human microvascular studies have been performed. Not much can be found in the literature on the toe NF, despite the fact that a large number of publications are devoted to the lower leg and foot. The closest observations reported are usually from the dorsal skin of the distal phalanx of the toes, close to, but not necessarily involving the NF and the endrow loops. Reportedly the mean width of the toe NF loops is significantly larger than in the finger.

Limiting Factors

The drawback of capillary observations in the skin, including the NF, relates to the problem of illumination: Only reflected light can be used here. Compared to microscopy performed with transmitted light, conventional capil-laroscopy allows capillaries to be seen only by the presence of RBC columns within them.

Only a few investigators have been able to obtain other details. Ehring and Schumann [2] succeeded in visualizing the capillary wall of NF capillaries by using a specialized optical and illumination system of Vonwiller. Mahler et al. [3] used fluorescein-tagged human albumin that helped to visualize plasma space and thus obtain a better estimate of the total intraluminal dimensions. Conventional measurements of NF capillary dimensions have been based on RBC columns.

In addition, reflections from the oil deposited on the skin interfere with photography, as does the very limited depth of field especially at low magnification. It should also be remembered that NF is a very specialized area of the skin that may not necessarily closely reflect microvascular structure and function elsewhere in the body. Despite all these shortcomings, NF capillary microscopy has yielded considerable information on human microvasculature in health and disease.

properly introduce the micropipette into the capillary loop. Unlike the completely noninvasive approach just discussed, minimal trauma is necessary, because the hard keratin layer is difficult to penetrate. The normal capillary pressure ranges from 10 to 22mmHg.

Capillary Permeability

Sodium fluorescein has been used most often to estimate capillary permeability. Although this agent also diffuses out in normal subjects, pathological changes can be estimated by the speed and pattern of this diffusion compared to healthy subjects.

Laser Doppler Blood Flow Measurements

This technique has often been performed on the dorsum of the distal phalanx, or on the proximal part of the NF concurrently with capillaroscopy. It is believed to measure skin blood flow in deeper layers and not the capillary blood flow.

More detailed information on methodology can be found in the book by Bollinger and Fagrell [4] and in a review article by Shore [5].


NF biopsy has been rarely performed, but, as seen in Figure 1, it can show NF structure better than the schematic illustrations often used. At higher magnification, finer details of capillary wall, dermoepidermal junction, and so on can be studied and compared to in vivo observations obtained in the same NF just before the biopsy [6].


In Vivo Microscopy

Recording of Capillaries and Their Blood Flow

Most studies of the human NF have been performed by in vivo microscopy, also called capillaroscopy, because usually the focus has been on capillaries only. A variety of microscopes, illumination techniques, and photographic systems have been used over the years to obtain well-focused, sharp still pictures.

To record capillary blood flow, by measuring RBC velocity, additional instrumentation was developed: first cinematographic, then video systems. Computer technology now allows automated analysis of these data. Normal RBC velocity ranges from 0.1 to 2.8mm/sec, with an average of 0.6mm/sec.

Unfortunately, the measurements are often taken from selected, nonrandom, capillaries: those that happen to be well focused. Therefore, the number of capillaries per NF and the number of nail folds studied vary.

Capillary Pressure

Instrumentation for capillary pressure measurement needs to be used in combination with capillaroscopy to

Essentials of Human Physiology

Essentials of Human Physiology

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