The term anemia, as it is generally used in clinical medicine, refers to a reduction below normal in the number of red corpuscles per cubic millimeter, the quantity of hemoglobin and the volume of packed cells per 100 ml of blood. The simplest way to determine the presence of anemia is to measure one or all of the above mentioned criteria. The most accurate procedure is the measurement of the packed cell volume, followed by the hemoglobin determination and lastly by the total red cell count. Using the data obtained one can calculate the various erythrocytic indicies such as the mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and the mean corpuscular hemoglobin concentration (MCHC).

The oxygen carrying capacity of the red blood cell is dependent upon its hemoglobin content which, in turn, requires iron and traces of copper and cobalt for its synthesis. Of course many other cofactors--amino acids, etc. are also necessary for hemoglobin synthesis. This report will be limited to metabolism per se (i.e.) from the time of ingestion to its location where hemoglobin is synthesized.

Anemia, or the anemic state, has not been reported in cetaceans so far as I am aware; however, there are published reports containing information which suggest the presence of anemia. Quay(l) reported on some blood studies of Beluga whales in which he found numerous nucleated red blood cells (85%) in the peripheral blood, in one of the three whales tested. We have also seen these metarubricytes in the peripheral blood of dolphins and whales which to our knowledge were not anemic.

Howell-Jolly bodies are also seen quite frequently. Perhaps they are incidental findings as is believed to be the case in the domestic cat. However, when their number increases this is an indication of an increased demand for oxygen carrying capacity and hence, extrusion of the cells from the bone marrow in a somewhat more immature state. Recently we also examined blood smears for Dr. Geraci from Beluga whales in the Hudson's Bay area and found nucleated red blood cells on numerous occasions. Perhaps the excitement of capture and sampling may have caused their appearance in the blood. We have also observed anisocytosis and polychromasia in some of our samples.

The total iron content of the body tends to remain, at least in man, within relatively narrow limits; otherwise siderosis or iron deficiency occurs. The largest portion of body iron is either bound in a porphyrin ring as a part of blood or muscle hemoglobin or, as one of the heme enzymes, or is laid aside as storage iron. The remainder, a very small portion, is present as ferrous ions or in transport in plasma where it is carried bound to a ß1 serum globulin (transferrin).The storage form of iron is ferritin or hemosiderin.

Iron in food of animal origin is present in conjugates mainly in the ferric state and as iron bound loosely to organic molecules such as citrate, lactate and amino acids; yet ferrous ions are more readily absorbed. Many factors affect the absorption of iron. It readily forms insoluble complexes with many dietary constituents especially in a medium which is not strongly acid. Iron phosphates are practically insoluble and consequently a diet high in phosphorus could interfere with its absorption. Excess calcium can inhibit iron assimilation. Ascorbic acid increases absorption of iron (reduces ferric to ferrous). The acidity of the stomach is supposed to play a role but this in laboratory animals is under dispute. Some believe that pancreatic secretion inhibits iron absorption.

The site of iron absorption is the small intestine, being greatest in the duodenum and decreasing caudally. This may be explained, in part at least, on the low pH which prevents auto-oxidation of ferrous iron to ferric hydroxide.

The absorption of iron has been believed to be regulated by the intestinal content of iron or the "mucosal block" theory; however, this is also being challenged at present. Nevertheless, the intestinal mucosa does play a very important role. As iron is absorbed by the intestinal mucosa it is incorporated into ferritin.

Iron enters the plasma not only from the intestine but also from the breakdown of hemoglobin by the reticulo-endothelial system.

Iron is carried by a specific plasma protein--transferrin--which has the mobility of a ß 1 globulin. Transferrin functions as a transport protein in that it shuttles iron atoms between tissues without being assimilated itself. In humans the total iron binding capacity of the plasma (TIBC) is 300-360 micrograms/100 ml and it is rare to find values below 250 or above 400 micro grams. Normally in man only about a third of the transferrin is saturated with iron. The normal content of iron in human plasma ranges from 60-200 micrograms/100 ml. The values that I found on 15 samples of dolphin blood examined were as follows:

TIBC 516 + 32 micrograms/100 ml Serum Iron
227 + 18 micrograms/100 ml

Serum iron is reduced in iron deficiency, infections, during periods of active erythropoiesis, some malignancies. Increased levels occur when there is increased red cell destruction, decreased blood formation.

An increase in TIBC occurs in acute or chronic blood loss, or in an iron deficiency. A decrease in TIBC occurs mostly in acute and chronic infections.

Cetaceans according to Slijper (3) have red cell counts between 7-11 million/cmm; however, on a basis of our studies as well as by many others the actual count is between 3-5 million/cmm. Knoll (4) also stated that the red blood count of cetaceans was very high. Andersen (5) (1965) found red cell counts of 5 + .75 millions in the Harbour porpoise (Phocaena phocaena); however, Morimoto et al (2) (1921) reported 8.5 million in the same species. Morimoto et al (2) (1921) also reported total. red cell counts of 6.85 million/cmm in the Bottlenose dolphin. Medway and Geraci (6) (1964) found 3.49 +.287 million/cmm in the same species. Morimoto et al (2) (1921) also reported red cell counts of 8 million/cmm in the sperm whale and 7 million/cmm in the Blue Whale, Common Rorqual and the Humpback Whale. Medway and Moldovan (7) (1966) found red cell counts of 3.71 ± 38 million/cmm in the North Atlantic Pilot Whale. From these data one can deduce that either the more recent figures are erroneous or the early ones are, or else all the recently studied animals were borderline anemic.

Andersen (8) also stated in a letter, which probably a number of you also received, that newly acquired animals tend to have higher packed cell volumes and hemoglobins than they have 5 months later. The reason for this he does not know. He also noted a drop in serum Fe and TIBC. He asked if anything is known about the effect of various species of fish being fed. For example, it is known (9) that feeding raw fish such as whiting (Gadus merlangus), coalfish (Gadus virens) and hake (Merlucius vulgaris) to mink kits produces anemia. It is a microcytic, hypochromic, iron deficiency anemia. By feeding boiled fish of the same species anemia does not develop. Supplementing the raw fish with vitamins and trace elements did not give any response. I do not know if a similar situation could occur with captive cetaceans where a limited number of species of fish are fed. It is hypothesized that something in the raw fish binds the iron and so makes it unavailable to the animal.

Andersen (5) also showed graphically the hemoglobin response of the effect of treating two of his anemic animals with iron.

It is also known that an anemia develops in hypothyroidism. Iodine deficiency may not be a problem where sea water is used in the pools, but may be a real problem in artificial systems.

References

1. Quay, W. B.: The Blood Cells of Cetacea with Particular Reference to the Beluga Delphinapterus leucas. Pallas, 1776. Säugetierkundliche Mitteilungen. 2 (1954): 49-54.
2. Morimoto, Y., Takata, M. and Sudzuki, M.: Untersuchungen über Cetacea. I Vorversuche. Tohoku J. Exp. Med. 2 (1921).
3. Slijper, E. J.: Whales. Basic Books Inc., New York, 1962.
4. Knoll, W.: Das morphologische Blutbild der Säugetiere III Sugetiere. Sugetiere. der Sugetiere. 46, 1939.
5. Andersen, S.: The Physiological Range of the Formed Elements in the Peripheral Blood of the Harbour Porpoise, Sugetiere. in Captivity. Nord. Sugetiere. 18 Sugetiere. 51-65.
6. Medway, W. and Sugetiere. J. R.: Hematology of the Bottlenose Dolphin Sugetiere. truncatus) Am. J. Sugetiere. 207 Sugetiere. 1367-1370.
7. Medway, W. and Sugetiere. F.: Blood Studies on the North Atlantic Pilot Sugetiere. Whale, Sugetiere. Sugetiere. Sugetiere. 1809). Sugetiere. Zoo. 39 Sugetiere. 110-116.
8. Andersen, S.: Personal Communication, 1967.
9. Havre, G. N., Helgebostad, A. and Sugetiere. F.: Iron Resorption in Fish-Induced Sugetiere in Mink. Nature 215 Sugetiere. 187-188.