CLINICAL ANATOMY AND PHYSIOLOGY OF PAEDIATRIC PATIENTS

2.1 Respiratory system

The adult mammalian lung is highly conserved in many respects among monotreme, marsupial and eutherian spe­cies. However, significant differences are seen in paediat­ric lung structure and function among these groups and this is explained largely by disparate developmental rates (Ferner et al.

Lung development in marsupials is generally slow. During the early postnatal period, the saccules become subdivided by septal crests and decrease in size. In the tammar wallaby (Notamacropus eugenii), the first true alveoli, identified by the presence of single-capillary septa, are present at 65 d and a typical alveolised lung structure, characterised by the presence of respiratory bronchioles, alveolar ducts and alveolar sacs can be seen at 142 d (Mess and Ferner 2010). Postnatal lung develop­ment in altricial eutherians is more rapid and the attain­ment of alveolised lungs and a corresponding dramatic increase in lung surface area is thought to influence the observed enhanced metabolic trajectory seen at this time.

Paediatric mammals have less alveolar surface area than adults and as a result tend to have higher minute volumes. This higher minute volume is achieved by an increase in tidal volume and/or an increase in respiratory rate as demonstrated by juvenile red kangaroos (Osphranter rufus) at thermal extremes (Munn et al. 2007). Because of their pliable rib cage and immaturity of muscles associated with ventilation there is greater poten­tial for respiratory fatigue (Sisak 2007).

2.2 Cardiovascular system

The immaturity of the cardiovascular system in young animals justifies close monitoring of heart rate during clinical evaluation (Sisak 2007). The paediatric cardiovas­cular system is a low-pressure system resulting from lower myocardial contractile mass, decreased ventricular com­pliance and a relatively immature autonomic nervous system. There is limited ability to increase cardiac output by altering cardiac contractility or by affecting preload. Preservation of cardiac output is therefore primarily dependent upon increased heart rate and maintenance of low systemic vascular resistance. As stroke volume is fixed, increases in preload and afterload are poorly tolerated and young animals are less able to tolerate blood loss compared with adults. Bradycardia in an ailing paediatric patient that fails to resolve with stabilisation is likely to signal an inabil­ity to mount an appropriate physiological response and should be considered a poor prognostic indicator.

Marsupial neonates have a form of haemoglobin that is adapted to the lower oxygen and higher carbon dioxide concentrations of pouch air. They also have fetal haema­tological characteristics, with up to 100% nucleated erythrocytes at 1 d of age in some species, decreasing over time (Clark 2004).

In marsupials, haematopoiesis occurs in the liver before and after birth, with no haematopoiesis reported in the bone marrow or spleen when in utero (Old 2016).

2.3 Hepatic function

Immature hepatic function is an important consideration with respect to drug metabolism and toxin exposure. Care should be taken when prescribing drugs that undergo extensive hepatic metabolism in young animals.

Differences in albumin levels in paediatric patients compared with adults may influence the bioavailability and the half-life of toxins or drugs that are highly protein bound. Greater bilbies (Macrotis lagotis) have lower albu­min concentrations when young (Warren et al. 2015), whereas young brush-tailed rock-wallabies (Petrogale penicillata) and Tasmanian devils (Sarcophilus harrisii) are reported to have higher levels than adults (Barnes et al.

2.4 Renal function

For most species renal function is limited in the early paediatric phase and is compensated for by frequent (or continuous in the case of young marsupial PY) oral intake of milk. Renal immaturity has important implications for hydration status and drug elimination.

Neonatal and juvenile animals have reduced renal blood flow and therefore decreased glomerular filtration rates. Being orphaned or other problems associated with cessation of milk intake can rapidly result in dehydration. Water-soluble compounds have a decreased clearance and increased half-life, which is particularly problematic in dehydrated patients. Compounds affected by reduced renal clearance include aminoglycosides, cephalosporins, penicillins, tetracyclines, benzodiazepines, digoxin and sulfonamides (Petersen 2011). These drugs should be used cautiously and preferably only after the patient is adequately rehydrated.

2.5 Gastrointestinal system

Neonatal mammals need to be capable of consuming and digesting milk from birth. Menzies et al. (2009) demon­strated an early onset of gastric ghrelin expression in the tammar wallaby in concert with the presence of a func­tional stomach at an earlier stage than that of developmen­tally more mature eutherians. Gastric ghrelin secretion begins shortly after birth in the developing wallaby during a period of rapid hypothalamic growth. This suggests that ghrelin is important for regulating appetite, even in mar­supial neonates.

The establishment of a population of commensal microorganisms in the GIT is expected to protect the host from infection and colonisation by pathogens. This microbial population typically changes over the course of normal development. The numbers of bacterial species present in the various GI segments of tammar wallabies and common brush-tailed possums (Trichosurus vulpec­ula) was found to be low in animals aged 100 d or less, but there was a significant increase in microbial diversity in the caecum of the possums aged over 100 d (Lentle et al.

Neonatal carnivores do not have a fully developed gas­tric hydrochloric acid production system. They have a neutral gastric pH and may be more susceptible to infec­tion because of the loss of the protective gastric acid bar­rier. As the enteric system is still maturing in very young animals, GI motility may be controlled more by distension of the lumen with milk than by regular electrical activity (intestinal ‘pacemaker’ cells or interstitial cells of Cajal critical for contractile activity in adults are still maturing in very young animals). It is also influenced by body tem­perature.

Complex developmental changes occur in the GIT during postnatal life: these changes involve enteric neu­ronal, immune, epithelial and microbial systems all acting in concert. Early-life stress or adversity such as maternal separation and early weaning can have serious and long-lasting implications for intestinal function and disease susceptibility by influencing each of these com­ponents and their interactions (Pohl et al. 2015). Weaning is a particularly vulnerable period as the animal adapts to a sudden exposure to antigens and changes in microbial community. This is a common stage for GI problems to develop, particularly in hand-reared orphans.

2.6 Skin

Neonatal marsupials are furless, capable of cutaneous respiration (Simpson et al. 2011) and have an outer layer of developing epidermis called the periderm (Edwards et al. 2012). Neonatal and young juvenile skin is thin and has a large water component, which greatly increases the risk of dehydration and skin damage if not protected and enhances the absorption of topical medications and toxins. Furless orphaned PY must be maintained in a rel­atively humid environment and require regular applica­tion of moisturiser to prevent the skin drying out.

2.7 Immune function

A variety of strategies exist regarding immune protection of mammalian young. The neonatal and juvenile period is a time of exposure to a wide range of potential pathogens and the immune system develops and changes in response to stimuli throughout development. The importance and nature of pre- and/or postnatal transfer of immunoglobu­lins from the dam to the offspring and the development of the innate immune system varies between species.

Marsupial immune responses were previously consid­ered primitive, but recent work has demonstrated that the marsupial immune system is, in fact, complex and on par with that of eutherian mammals (Belov et al.

Fig. 15.1. Complementary protective mechanisms for marsupial PY. Dashed lines indicate period of transition or reduction in importance/ activity. Ig = immunoglobulins. Adapted from Edwards etal. 2012.

protection strategies, such as immune compounds in milk, prenatal transfer of immunoglobulins, antimicro­bial compounds secreted in the pouch and chemical or mechanical cleaning of the pouch and PY (Cheng and Belov 2017) (Fig. 15.1).

Innate immunity involves the production of cathelici­dins (antimicrobial peptides) and the development of lymphoid tissues and blood cells (Edwards et al. 2012). These are discussed in more detail in Chapter 7.

The pattern of marsupial milk secretion is complex, with species-specific variation. Milk contains immuno­globulins, lysozyme, transferrin and immune cells. It is believed that although these protective compounds are variably present in milk throughout pouch life, there are two distinct periods where there is enhanced transfer of immunoglobulins to the PY from the mammary gland: the first is a colostral phase (0-1 d), which is thought to provide the newborn with significant immune protection and the second occurs later during pouch life to provide additional protection to the juvenile as it exits the pouch for the first time (Borthwick et al. 2014). Passive immu­nity and the development of the marsupial immune system are described in McCracken (2008).

Orphans face particular challenges because they lose most maternal immunoglobulins by ~4 wk after separa­tion from the mother (McCracken 2008). They are reared in the absence of the protective compounds present within the natural pouch environment and artificial for­mulae do not contain the cocktail of immune-modulating compounds present in natural milk.

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