Spleen

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Spleen
Illu spleen.jpg
The human spleen is located in the upper left abdomen, behind the stomach
Details
System Immune system (Lymphatic system)
Artery Splenic artery
Vein Splenic vein
Nerve Splenic plexus
Identifiers
Latin splen, lien
MeSH D013154
TA98 A13.2.01.001
TA2 5159
FMA 7196
Anatomical terminology
A 3D medical animation still of spleen structure & exact location 3D Medical Animation Spleen Anatomy.jpg
A 3D medical animation still of spleen structure & exact location

The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes from Ancient Greek σπλήν (splḗn). [1]

Contents

The spleen plays very important roles in regard to red blood cells (erythrocytes) and the immune system. [2] It removes old red blood cells and holds a reserve of blood, which can be valuable in case of hemorrhagic shock, and also recycles iron. As a part of the mononuclear phagocyte system, it metabolizes hemoglobin removed from senescent red blood cells. The globin portion of hemoglobin is degraded to its constitutive amino acids, and the heme portion is metabolized to bilirubin, which is removed in the liver. [3] [4]

The spleen houses antibody-producing lymphocytes in its white pulp and monocytes which remove antibody-coated bacteria and antibody-coated blood cells by way of blood and lymph node circulation. These monocytes, upon moving to injured tissue (such as the heart after myocardial infarction), turn into dendritic cells and macrophages while promoting tissue healing. [5] [6] [7] The spleen is a center of activity of the mononuclear phagocyte system and is analogous to a large lymph node, as its absence causes a predisposition to certain infections. [8] [4]

In humans, the spleen is purple in color and is in the left upper quadrant of the abdomen. [3] [9]

Anatomy

The spleen is underneath the left part of the diaphragm, and has a smooth, convex surface that faces the diaphragm. It is underneath the ninth, tenth, and eleventh ribs. The other side of the spleen is divided by a ridge into two regions: an anterior gastric portion, and a posterior renal portion. The gastric surface is directed forward, upward, and toward the middle, is broad and concave, and is in contact with the posterior wall of the stomach. Below this it is in contact with the tail of the pancreas. The renal surface is directed medialward and downward. It is somewhat flattened, considerably narrower than the gastric surface, and is in relation with the upper part of the anterior surface of the left kidney and occasionally with the left adrenal gland.

There are four ligaments attached to the spleen: gastrosplenic ligament, splenorenal ligament, colicosplenic ligament, and phrenocolic ligament. [10]

Measurements

90% confidence interval of spleen length by abdominal ultrasonography by height of the person [11]
HeightSpleen length
WomenMen
155–159 cm6.4–12 cm
160–164 cm7.4–12.2 cm8.9–11.3 cm
165–169 cm7.5–11.9 cm8.5–12.5 cm
170–174 cm8.3–13.0 cm8.6–13.1 cm
175–179 cm8.1–12.3 cm8.6–13.4 cm
180–184 cm9.3–13.4 cm
185–189 cm9.3–13.6 cm
190–194 cm9.7–14.3 cm
195–199 cm10.2–14.4 cm

The spleen, in healthy adult humans, is approximately 7 to 14 centimetres (3 to 5+1⁄2 in) in length.

An easy way to remember the anatomy of the spleen is the 1×3×5×7×9×10×11 rule. The spleen is 1 by 3 by 5 inches (3 by 8 by 13 cm), weighs approximately 7 oz (200 g), and lies between the 9th and 11th ribs on the left-hand side and along the axis of 10th rib. The weight varies between 1 oz (28 g) and 8 oz (230 g) (standard reference range), [12] correlating mainly to height, body weight and degree of acute congestion but not to sex or age. [13]

Blood supply

Visceral surface of the spleen Gray1188.png
Visceral surface of the spleen

Near the middle of the spleen is a long fissure, the hilum, which is the point of attachment for the gastrosplenic ligament and the point of insertion for the splenic artery and splenic vein. There are other openings present for lymphatic vessels and nerves.

Like the thymus, the spleen possesses only efferent lymphatic vessels. The spleen is part of the lymphatic system. Both the short gastric arteries and the splenic artery supply it with blood. [14]

The germinal centers are supplied by arterioles called penicilliary radicles. [15]

Nerve supply

The spleen is innervated by the splenic plexus, which connects a branch of the celiac ganglia to the vagus nerve.

The underlying central nervous processes coordinating the spleen's function seem to be embedded into the Hypothalamic-pituitary-adrenal-axis, and the brainstem, especially the subfornical organ. [16]

Development

The spleen is unique in respect to its development within the gut. While most of the gut organs are endodermally derived, the spleen is derived from mesenchymal tissue. [17] Specifically, the spleen forms within, and from, the dorsal mesentery. However, it still shares the same blood supply—the celiac trunk—as the foregut organs.

Function

Pulp

Micrograph of splenic tissue showing the red pulp (red), white pulp (blue) and a thickened inflamed capsule (mostly pink - top of image). H&E stain. Spleen hyaloserositis - low mag.jpg
Micrograph of splenic tissue showing the red pulp (red), white pulp (blue) and a thickened inflamed capsule (mostly pink – top of image). H&E stain.
The spleen contains two different tissues, white pulp (A) and red pulp (B). The white pulp functions in producing and growing immune and blood cells. The red pulp functions in filtering blood of antigens, microorganisms, and defective or worn-out red blood cells. Red Pulp and White Pulp of the Spleen.jpg
The spleen contains two different tissues, white pulp (A) and red pulp (B). The white pulp functions in producing and growing immune and blood cells. The red pulp functions in filtering blood of antigens, microorganisms, and defective or worn-out red blood cells.
AreaFunctionComposition
red pulp Mechanical filtration of red blood cells. In mice: Reserve of monocytes [5]
white pulp Active immune response through humoral and cell-mediated pathways.Composed of nodules, called Malpighian corpuscles. These are composed of:

Other

Other functions of the spleen are less prominent, especially in the healthy adult:

Clinical significance

Thalassemia enlarged spleen taken after splenectomy Spleen after spleenectomy.jpg
Thalassemia enlarged spleen taken after splenectomy

Enlarged spleen

Enlargement of the spleen is known as splenomegaly. It may be caused by sickle cell anemia, sarcoidosis, malaria, bacterial endocarditis, leukemia, polycythemia vera, pernicious anemia, Gaucher's disease, leishmaniasis, Hodgkin's disease, Banti's disease, hereditary spherocytosis, cysts, glandular fever (mononucleosis or 'Mono' caused by the Epstein–Barr virus, infection from cytomegalovirus), and tumours. Primary tumors of the spleen include hemangiomas and hemangiosarcomas. Marked splenomegaly may result in the spleen occupying a large portion of the left side of the abdomen.

The spleen is the largest collection of lymphoid tissue in the body. It is normally palpable in preterm infants, in 30% of normal, full-term neonates, and in 5% to 10% of infants and toddlers. A spleen easily palpable below the costal margin in any child over the age of 3–4 years should be considered abnormal until proven otherwise.

Splenomegaly can result from antigenic stimulation (e.g., infection), obstruction of blood flow (e.g., portal vein obstruction), underlying functional abnormality (e.g., hemolytic anemia), or infiltration (e.g., leukemia or storage disease, such as Gaucher's disease). The most common cause of acute splenomegaly in children is viral infection, which is transient and usually moderate. Basic work-up for acute splenomegaly includes a complete blood count with differential, platelet count, and reticulocyte and atypical lymphocyte counts to exclude hemolytic anemia and leukemia. Assessment of IgM antibodies to viral capsid antigen (a rising titer) is indicated to confirm Epstein–Barr virus or cytomegalovirus. Other infections should be excluded if these tests are negative.

Splenic injury

Trauma, such as a road traffic collision, can cause rupture of the spleen, which is a situation requiring immediate medical attention.

Asplenia

Asplenia refers to a non-functioning spleen, which may be congenital, or caused by traumatic injury, surgical resection (splenectomy) or a disease such as sickle cell anaemia. Hyposplenia refers to a partially functioning spleen. These conditions may cause [6] a modest increase in circulating white blood cells and platelets, a diminished response to some vaccines, and an increased susceptibility to infection. In particular, there is an increased risk of sepsis from polysaccharide encapsulated bacteria. Encapsulated bacteria inhibit binding of complement or prevent complement assembled on the capsule from interacting with macrophage receptors. Phagocytosis needs natural antibodies, which are immunoglobulins that facilitate phagocytosis either directly or by complement deposition on the capsule. They are produced by IgM memory B cells (a subtype of B cells) in the marginal zone of the spleen. [22] [23]

A splenectomy (removal of the spleen) results in a greatly diminished frequency of memory B cells. [24] A 28-year follow-up of 740 World War II veterans whose spleens were removed on the battlefield showed a significant increase in the usual death rate from pneumonia (6 rather than the expected 1.3) and an increase in the death rate from ischemic heart disease (41 rather than the expected 30), but not from other conditions. [25]

Accessory spleen

An accessory spleen is a small splenic nodule extra to the spleen usually formed in early embryogenesis. Accessory spleens are found in approximately 10 percent of the population [26] and are typically around 1 centimeter in diameter. Splenosis is a condition where displaced pieces of splenic tissue (often following trauma or splenectomy) autotransplant in the abdominal cavity as accessory spleens. [27]

Polysplenia is a congenital disease manifested by multiple small accessory spleens, [28] rather than a single, full-sized, normal spleen. Polysplenia sometimes occurs alone, but it is often accompanied by other developmental abnormalities such as intestinal malrotation or biliary atresia, or cardiac abnormalities, such as dextrocardia. These accessory spleens are non-functional.

Infarction

Splenic infarction is a condition in which blood flow supply to the spleen is compromised, [29] leading to partial or complete infarction (tissue death due to oxygen shortage) in the organ. [30]

Splenic infarction occurs when the splenic artery or one of its branches are occluded, for example by a blood clot. Although it can occur asymptomatically, the typical symptom is severe pain in the left upper quadrant of the abdomen, sometimes radiating to the left shoulder. Fever and chills develop in some cases. [31] It has to be differentiated from other causes of acute abdomen.

Hyaloserositis

The spleen may be affected by hyaloserositis, in which it is coated with fibrous hyaline. [32] [33]

Society and culture

There has been a long and varied history of misconceptions regarding the physiological role of the spleen, and it has often been seen as a reservoir for juices closely linked to digestion. [34] In various cultures, the organ has been linked to melancholia, due to the influence of ancient Greek medicine and the associated doctrine of humourism, in which the spleen was believed to be a reservoir for an elusive fluid known as "black bile" (one of the four humours). [34] The spleen also plays an important role in traditional Chinese medicine, where it is considered to be a key organ that displays the Yin aspect of the Earth element (its Yang counterpart is the stomach). In contrast, the Talmud (tractate Berachoth 61b) refers to the spleen as the organ of laughter while possibly suggesting a link with the humoral view of the organ.

Etymologically, spleen comes from the Ancient Greek σπλήν (splḗn), where it was the idiomatic equivalent of the heart in modern English. Persius, in his satires, associated spleen with immoderate laughter. [35]

In English, William Shakespeare frequently used the word spleen to signify melancholy, but also caprice and merriment. [35] In Julius Caesar , he uses the spleen to describe Cassius's irritable nature:

Must I observe you? must I stand and crouch
Under your testy humour? By the gods
You shall digest the venom of your spleen,
Though it do split you; for, from this day forth,
I'll use you for my mirth, yea, for my laughter,
When you are waspish. [36]

The spleen, as a byword for melancholy, has also been considered an actual disease. [37] In the early 18th century, the physician Richard Blackmore considered it to be one of the two most prevalent diseases in England (along with consumption). [37] In 1701, Anne Finch (later, Countess of Winchilsea) had published a Pindaric ode, The Spleen, drawing on her first-hand experiences of an affliction which, at the time, also had a reputation of being a fashionably upper-class disease of the English. [38] Both Blackmore and George Cheyne treated this malady as the male equivalent of "the vapours", while preferring the more learned terms "hypochondriasis" and "hysteria". [37] [39] [40] In the late 18th century, the German word Spleen came to denote eccentric and hypochondriac tendencies that were thought to be characteristic of English people. [35]

In French, "splénétique" refers to a state of pensive sadness or melancholy. This usage was popularised by the poems of Charles Baudelaire (1821–1867) and his collection Le Spleen de Paris , but it was also present in earlier 19th-century Romantic literature.

Food

The spleen is one of the many organs that may be included in offal. It is not widely eaten as a principal ingredient, but cow spleen sandwiches are eaten in Sicilian cuisine. [41] Chicken spleen is one of the main ingredients of Jerusalem mixed grill. [42]

Other animals

Laparoscopic view of a horse's spleen (the purple and grey mottled organ) Horse spleen laparoscopic.jpg
Laparoscopic view of a horse's spleen (the purple and grey mottled organ)

In cartilaginous and ray-finned fish, the spleen consists primarily of red pulp and is normally somewhat elongated, as it lies inside the serosal lining of the intestine. In many amphibians, especially frogs, it has the more rounded form and there is often a greater quantity of white pulp. [43]

In reptiles, birds, and mammals, white pulp is always relatively plentiful, and in birds and mammals the spleen is typically rounded, but it adjusts its shape somewhat to the arrangement of the surrounding organs. In most vertebrates, the spleen continues to produce red blood cells throughout life; only in mammals this function is lost in middle-aged adults. Many mammals have tiny spleen-like structures known as haemal nodes throughout the body that are presumed to have the same function as the spleen. [43] The spleens of aquatic mammals differ in some ways from those of fully land-dwelling mammals; in general they are bluish in colour. In cetaceans and manatees they tend to be quite small, but in deep diving pinnipeds, they can be massive, due to their function of storing red blood cells.

The only vertebrates lacking a spleen are the lampreys and hagfishes (the early-branching Cyclostomata, or jawless fishes). Even in these animals, there is a diffuse layer of haematopoeitic tissue within the gut wall, which has a similar structure to red pulp and is presumed homologous with the spleen of higher vertebrates. [43]

In mice the spleen stores half the body's monocytes so that upon injury, they can migrate to the injured tissue and transform into dendritic cells and macrophages to assist wound healing. [5]

Additional images

See also

Related Research Articles

<span class="mw-page-title-main">Haematopoiesis</span> Formation of blood cellular components

Haematopoiesis is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells. In a healthy adult human, roughly ten billion to a hundred billion new blood cells are produced per day, in order to maintain steady state levels in the peripheral circulation.

<span class="mw-page-title-main">Lymphatic system</span> Organ system in vertebrates

The lymphatic system, or lymphoid system, is an organ system in vertebrates that is part of the immune system, and complementary to the circulatory system. It consists of a large network of lymphatic vessels, lymph nodes, lymphoid organs, lymphoid tissues and lymph. Lymph is a clear fluid carried by the lymphatic vessels back to the heart for re-circulation.

<span class="mw-page-title-main">Lymph node</span> Organ of the lymphatic system

A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that include B and T cells. Lymph nodes are important for the proper functioning of the immune system, acting as filters for foreign particles including cancer cells, but have no detoxification function.

<span class="mw-page-title-main">Lymphocytosis</span> Medical condition

Lymphocytosis is an increase in the number or proportion of lymphocytes in the blood. Absolute lymphocytosis is the condition where there is an increase in the lymphocyte count beyond the normal range while relative lymphocytosis refers to the condition where the proportion of lymphocytes relative to white blood cell count is above the normal range. In adults, absolute lymphocytosis is present when the lymphocyte count is greater than 5000 per microliter (5.0 x 109/L), in older children greater than 7000 per microliter and in infants greater than 9000 per microliter. Lymphocytes normally represent 20% to 40% of circulating white blood cells. When the percentage of lymphocytes exceeds 40%, it is recognized as relative lymphocytosis.

<span class="mw-page-title-main">Splenectomy</span> Surgical removal of the spleen

A splenectomy is the surgical procedure that partially or completely removes the spleen. The spleen is an important organ in regard to immunological function due to its ability to efficiently destroy encapsulated bacteria. Therefore, removal of the spleen runs the risk of overwhelming post-splenectomy infection, a medical emergency and rapidly fatal disease caused by the inability of the body's immune system to properly fight infection following splenectomy or asplenia.

<span class="mw-page-title-main">Hereditary spherocytosis</span> Medical condition

Hereditary spherocytosis (HS) is a congenital hemolytic disorder, wherein a genetic mutation coding for a structural membrane protein phenotype leads to a spherical shaping of erythrocytic cellular morphology. As erythrocytes are sphere-shaped (spherocytosis), rather than the normal biconcave disk-shaped, their morphology interferes with these cells' abilities to be flexible during circulation throughout the entirety of the body - arteries, arterioles, capillaries, venules, veins, and organs. This difference in shape also makes the red blood cells more prone to rupture under osmotic and/or mechanical stress. Cells with these dysfunctional proteins are degraded in the spleen, which leads to a shortage of erythrocytes resulting in hemolytic anemia.

Asplenia refers to the absence of normal spleen function and is associated with some serious infection risks. Hyposplenism is used to describe reduced ('hypo-') splenic functioning, but not as severely affected as with asplenism.

<span class="mw-page-title-main">Splenomegaly</span> Medical condition

Splenomegaly is an enlargement of the spleen. The spleen usually lies in the left upper quadrant (LUQ) of the human abdomen. Splenomegaly is one of the four cardinal signs of hypersplenism which include: some reduction in number of circulating blood cells affecting granulocytes, erythrocytes or platelets in any combination; a compensatory proliferative response in the bone marrow; and the potential for correction of these abnormalities by splenectomy. Splenomegaly is usually associated with increased workload, which suggests that it is a response to hyperfunction. It is therefore not surprising that splenomegaly is associated with any disease process that involves abnormal red blood cells being destroyed in the spleen. Other common causes include congestion due to portal hypertension and infiltration by leukemias and lymphomas. Thus, the finding of an enlarged spleen, along with caput medusae, is an important sign of portal hypertension.

An autosplenectomy is a negative outcome of disease and occurs when a disease damages the spleen to such an extent that it becomes shrunken and non-functional. The spleen is an important immunological organ that acts as a filter for red blood cells, triggers phagocytosis of invaders, and mounts an immunological response when necessary. Lack of a spleen, called asplenia, can occur by autosplenectomy or the surgical counterpart, splenectomy. Asplenia can increase susceptibility to infection. Autosplenectomy can occur in cases of sickle-cell disease where the misshapen cells block blood flow to the spleen, causing scarring and eventual atrophy of the organ. Autosplenectomy is a rare condition that is linked to certain diseases but is not a common occurrence. It is also seen in systemic lupus erythematosus (SLE).

<span class="mw-page-title-main">Splenic injury</span> Medical condition

A splenic injury, which includes a ruptured spleen, is any injury to the spleen. The rupture of a normal spleen can be caused by trauma, such as a traffic collision.

Felty's syndrome (FS), also called Felty syndrome, is rare autoimmune disease characterized by the triad of rheumatoid arthritis, enlargement of the spleen and low neutrophil count. The condition is more common in those aged 50–70 years, specifically more prevalent in females than males, and more so in Caucasians than those of African descent. It is a deforming disease that causes many complications for the individual.

<span class="mw-page-title-main">Kurloff cell</span> Cells found in the blood and organs of guinea pigs and capybara

Kurloff cells were described as mononuclear cells in the peripheral blood and organs of the guinea pig, capybara, paca, agouti and cavie. The Kurloff cell contains a characteristic proteoglycan-containing inclusion body. In the guinea pig, Kurloff cells are more numerous in the adult female than the adult male. A marked increase in the number of circulating Kurloff cells is present in the peripheral blood during pregnancy and after estrogen treatment in male and female animals. A relatively smaller number of cells take place in immature, non-pregnant, and non-estrogen-treated animals. The exact function of Kurloff cells remains unknown, but it has some of the characteristics of both monocytes and lymphocytes. In guinea-pigs, it has been proposed that Kurloff cells mainly involve in the function of the immune system, such as acting as a natural killer cell and preventing damage to the trophoblast by maternal defensive cells. Also, Kurloff cells present antibody-dependent cytotoxic activity in vitro.

<span class="mw-page-title-main">White pulp</span> Type of tissue in the spleen

White pulp is a histological designation for regions of the spleen, that encompasses approximately 25% of splenic tissue. White pulp consists entirely of lymphoid tissue.

<span class="mw-page-title-main">Red pulp</span> Type of tissue in the spleen

The red pulp of the spleen is composed of connective tissue known also as the cords of Billroth and many splenic sinusoids that are engorged with blood, giving it a red color. Its primary function is to filter the blood of antigens, microorganisms, and defective or worn-out red blood cells.

<span class="mw-page-title-main">Splenic infarction</span> Medical condition

Splenic infarction is a condition in which blood flow supply to the spleen is compromised, leading to partial or complete infarction in the organ. Splenic infarction occurs when the splenic artery or one of its branches are occluded, for example by a blood clot.

Spleen transplantation is the transfer of spleen or its fragments from one individual to another. It is under research for induction of immunological tolerance for other transplanted organs. Success has been achieved in rodent models. Recently, evidence has been obtained for a tolerogenic effect of a spleen transplant in miniature swine. Also, the spleen harbors primitive hematopoietic progenitor cells. Spleen transplantation has been performed on humans with mixed results.

<span class="mw-page-title-main">Accessory spleen</span> Small nodule found apart from the main body of the spleen

An accessory spleen is a small nodule of splenic tissue found apart from the main body of the spleen. Accessory spleens are found in approximately 10 percent of the population and are typically around 1 centimetre in diameter. They may resemble a lymph node or a small spleen. They form either by the result of developmental anomalies or trauma. They are medically significant in that they may result in interpretation errors in diagnostic imaging or continued symptoms after therapeutic splenectomy. Polysplenia is the presence of multiple accessory spleens rather than one normal spleen.

<span class="mw-page-title-main">B-cell prolymphocytic leukemia</span> Medical condition

B-cell prolymphocytic leukemia, referred to as B-PLL, is a rare blood cancer. It is a more aggressive, but still treatable, form of leukemia.

<span class="mw-page-title-main">Marginal zone B-cell lymphoma</span> Group of lymphomas

Marginal zone B-cell lymphomas, also known as marginal zone lymphomas (MZLs), are a heterogeneous group of lymphomas that derive from the malignant transformation of marginal zone B-cells. Marginal zone B cells are innate lymphoid cells that normally function by rapidly mounting IgM antibody immune responses to antigens such as those presented by infectious agents and damaged tissues. They are lymphocytes of the B-cell line that originate and mature in secondary lymphoid follicles and then move to the marginal zones of mucosa-associated lymphoid tissue, the spleen, or lymph nodes. Mucosa-associated lymphoid tissue is a diffuse system of small concentrations of lymphoid tissue found in various submucosal membrane sites of the body such as the gastrointestinal tract, mouth, nasal cavity, pharynx, thyroid gland, breast, lung, salivary glands, eye, skin and the human spleen.

<span class="mw-page-title-main">White blood cell</span> Type of cells of the immunological system

White blood cells, also called leukocytes or leucocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. White blood cells include three main subtypes; granulocytes, lymphocytes and monocytes.

References

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  25. ↑ Dennis Robinette, C.; Fraumeni, Josephf. (1977). "Splenectomy and Subsequent Mortality in Veterans of the 1939–45 War". The Lancet. 310 (8029): 127–29. doi:10.1016/S0140-6736(77)90132-5. PMID   69206. S2CID   38605411.
  26. ↑ Moore, Keith L. (1992). Clinically Oriented Anatomy (3rd ed.). Baltimore: Williams & Wilkins. p. 187. ISBN   978-0-683-06133-8.
  27. ↑ Abu Hilal M; Harb A; Zeidan B; Steadman B; Primrose JN; Pearce NW (January 5, 2009). "Hepatic splenosis mimicking HCC in a patient with hepatitis C liver cirrhosis and mildly raised alpha feto protein; the important role of explorative laparoscopy". World Journal of Surgical Oncology. 7 (1): 1. doi:10.1186/1477-7819-7-1. PMC   2630926 . PMID   19123935.
  28. ↑ " polysplenia " at Dorland's Medical Dictionary
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  30. ↑ Jaroch MT, Broughan TA, Hermann RE (October 1986). "The natural history of splenic infarction". Surgery. 100 (4): 743–50. PMID   3764696.
  31. ↑ Nores, M1; Phillips, EH; Morgenstern, L; Hiatt, JR (February 1998). "The Clinical Spectrum of Splenic Infarction". The American Surgeon . 64 (2): 182–88. PMID   9486895.
  32. ↑ "Hyaloserositis". Online Medical Dictionary. Accessed on: June 21, 2008.
  33. ↑ "Sugar-coated spleen". Drugs.com.
  34. 1 2 Riva MA, Ferraina F, Paleari A, Lenti MV, Di Sabatino A (2019). "From sadness to stiffness: the spleen's progress". Internal and Emergency Medicine. 14 (5): 739–743. doi:10.1007/s11739-019-02115-2. PMID   31152307. S2CID   172137672.
  35. 1 2 3 Stanley Eric (2002). "Polysemy and synomyny and how these concepts were understood from the eighteenth century onwards in treatises, and applied dictionaries of English". In Coleman J, McDermott A (ed.). Historical dictionaries and historical Dictionary Research: Papers from the international conference on historical lexicography and lexicology, at the University of Leicester, 2002. Germany: Walter de Gruyter. pp. 170–171. ISBN   978-3-11-091260-9.
  36. ↑ Julius Caesar by William Shakespeare Act 4:1
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  38. ↑ Rogers KM (1989). "Finch's "Candid Account" vs. Eighteenth–Century Theories of the Spleen". Mosaic: A Journal for the Interdisciplinary Study of Literature. 22 (1): 17–27. ISSN   0027-1276. JSTOR   24780450.
  39. ↑ Cheyne, George: The English Malady; or, A Treatise of Nervous Diseases of All Kinds, as Spleen, Vapours, Lowness of Spirits, Hypochondriacal and Hysterical Distempers with the Author's Own Case at Large, Dublin, 1733. Facsimile ed., ed. Eric T. Carlson, M.D., 1976, Scholars' Facsimiles & Reprints, ISBN   978-0-8201-1281-7
  40. ↑ Blackmore, Richard: Treatise of the spleen and vapors. London, 1725
  41. ↑ Rao, Tejal (2010-05-03). "Spleen Sandwiches: An Italian Tradition". The Atlantic. Retrieved 2022-01-03.
  42. ↑ Rogov, Daniel (2007-03-22). "Dining Out / Mixed Jerusalem grill in Tel Aviv". Haaretz. Retrieved 2022-01-03.
  43. 1 2 3 Romer, Alfred Sherwood; Parsons,, Thomas S. (1977). The Vertebrate Body. Philadelphia: Holt-Saunders International. pp. 410–11. ISBN   978-0-03-910284-5.{{cite book}}: CS1 maint: multiple names: authors list (link)
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