The Spleen

Anatomy of Spleen

White Pulp

Spleen Structure The white pulp is circular in structure and is made up mainly of lymphocytes. It functions in a manner similar to the nodules of the lymph node. The red pulp surrounds the white pulp and contains mainly red blood cells and macrophages. The main function of the red pulp is to phagocytize old red blood cells.

Red Pulp

Function  The spleen is a sophisticated filter that monitors and manages blood cells and immune functions  During fetal development the spleen produces red and white blood cells  By the fifth month of gestation the spleen no longer has hematopoietic function but retains the capacity throughout life  Red cells that pass through the spleen undergo a “cleaning” or repair  Abnormal and old cells are destroyed

Function  Reticulocytes loose their nuclear remnants and excess membrane before entering the circulation  RBC’s coated with IgG and IgM are removed and destroyed  The spleen is the site of destruction in autoimmune disease states (ITTP and hemolytic anemia)  Parasites such as malaria can be removed as well  The spleen is involved in specific and nonspecific immune responses (promotes phagocytosis and destruction of bacteria)

Sites of Haemopoiesis  Yolk sac  Liver and spleen  Bone marrow  Gradual replacement of active (red) marrow by tissue inactive (fatty)  Expansion can occur during increased need for cell production

Splenic Trauma  Diagnosis  Injury should be suspected in blunt upper abdominal injuries ( MVA and Bike)  Injuries are often associated with fractured ribs of the left chest  Splenic injuries can cause extensive and continued hemorrhage, others can cause subcapsular hematomas that are subject to rupture at any time  If splenic injury is suspected, admission to the hospital for monitoring is mandatory  The signs and symptoms of splenic trauma are those of hemoperitoneum (generalized LUQ pain)

Treatment of Ruptured Spleen  Splenic preservation operations  Partial splenectomy  Capsular repair  Non operative treatment

Delayed Rupture of the Spleen  Injury to the pulp sometimes cannot be contained indefinitely by the splenic capsule  The usual interval between injury and hemorrhage is within two weeks (longer intervals have been reported)  The incidence is between 15-30%  It is hoped that as imaging techniques improve the incidence will decrease

Splenosis  Is the auto transplantation of splenic tissue after splenic trauma  They vary from a few millimeters to several centimeters in diameter  May occur anywhere in the peritoneal cavity  Seldom causes symptoms and is usually discovered as an incidental finding at reoperation  Post splenectomy sepsis has renewed interest in splenosis

Causes of splenomegaly  Infection  Bacterial: Typhoid fever, endocarditis, septicemia, abscess  Viral:E-B virus, CMV, and others  Protozoal: Malaria, toxoplasmosis  Hematologic processes  Hemolytic anemia: Congenital, acquired  Extramedullary hematopoiesis: thalassemia, osteopetrosis, myelofibrosis  Neoplasms  Malignant: Leukemia, lymphoma, histiocytoses, metastatic tumors  Benign: Hemagioma, hamartoma  Metabolic diseases  Lipidosis: Niemann-Pick, Gaucher disease  Mucopolysaccharidosis infiltration: Histiocytosis  Congestion  Cirrhosis  Cysts  Miscellaneous

Hypersplenism  Refers to a variety of ill effects resulting from increased splenic function that may be improved by splenectomy  The criteria for diagnosis included:  Anemia, leukopenia, thrombocytopenia or a combination of the three  Compensatory bone marrow hyperplasia  Splenomegaly  Hypersplenism can be categorized as primary or secondary

Splenic Involvement in Hodgkin’s lymphoma  The probability of splenic involvement increases with increasing spleen size  The absence of splenomegaly does not exclude splenic involvement  Upon gross examination of the spleen a grayish white nodule ranging from several millimeters to several centimeters is apparent with Hodgkin’s disease  Liver involvement with Hodgkin’s disease rarely occurs in the absence of splenic disease

Felty’s Syndrome  Is a syndrome consisting of severe rheumatoid arthritis, granulocytopenia and splenomegaly  It usually occurs in patients with a long history of rheumatoid arthritis  Severe, persistent and recurrent infections are characteristic  Moderate splenomegaly is common  Splenectomy is effective in most patients

Gaucher’s Disease  Is a disorder of lipid metabolism that may result in massive splenomegaly and hypersplenism  Commonly found in the Jewish population  Diagnosis is made by finding the typical Gaucher’s cells in biopsy tissue  Massive splenomegaly is usually the most common form of presentation  The adult form is the most common form  Splenomegaly (subtotal) shows great benefits

Cysts and Tumors of the Spleen  The differential diagnosis of splenomegaly should include splenic masses and primary tumors (these conditions are rare however they must be considered)  Cystic lesions comprise parasitic and nonparasitic cysts  Parasitic cysts are due almost exclusively to echinococcal disease (rare in the United States)  Nonparasitic cysts are classified as primary (true) which have an epithelial lining or pseudocysts (more common  Symptoms of splenic cysts are vague and are caused primarily by mass effect (compression of adjacent viscera)

Cysts and Tumors of the Spleen  Selected nonparasitic cyst may be managed by aspiration  Splenectomy should be performed for all large cyst and those with an uncertain diagnosis  Malignant and benign primary tumors of the spleen are rare  Most primary malignant tumors are angiosarcomas

Infectious Mononucleosis  A disease characterized by fever, sore throat, lymphadenopathy and atypical lymphocytes  Most patients are young  Clinical symptoms are similar to those of a severe upper respiratory tract infection  The spleen is enlarged and palpable in over 50% of patients  Splenic rupture may occur

Incidental Splenectomy  The spleen is vulnerable to injury during operative procedures in the upper abdomen  When the splenic capsule is torn, splenectomy is frequently performed  Morbidity and mortality is higher with iatrogenic injury requiring splenectomy

Splenectomy  Prior to removing the spleen specific preoperative preparation is necessary  All patients should receive polyvalent pneumococcal vaccine, polyvalent meningococcal vaccine and Haemophilus influenzae type b conjugant vaccine  Blood and blood products should be available well in advance of surgery

Blood Compositional Changes in the Asplenic or Hyposplenic Patient  The absence of functional splenic tissue results in characteristic changes in the circulating blood  Some of these are predictable and desirable results  These changes are considered a measure of its success when splenectomy is performed for a hematologic disease  Howell-Jolly bodies (nuclear remnants) and thrombocytosis (desired result)  Other findings include: target cells, acanthocytes (spur cells), Heinz bodies (denatured hemoglobin) and stippled red cells

Postsplenectomy Sepsis  Asplenic patients have an increased susceptibility to the development of overwhelming infection  The risk of sepsis is approximately 60 times greater than normal after splenectomy  The risk is greatest in children younger than four years of age  The risk of sepsis is higher among patients requiring splenectomy for inherited diseases  The risk of sepsis after splenectomy is lowest after trauma

Postsplenectomy Sepsis  Postsplenectomy sepsis syndrome typically occurs in a previously healthy individual after a mild upper respiratory tract infection associated with fever  Within hours, nausea, vomiting, headache, confusion, shock and coma can occur; death follows within 24 hours  The nature of the syndrome makes it difficult to diagnose early enough for therapy to be effective

Postsplenectomy Sepsis  The most common bacteria isolated our streptococcus pneumoniae, Neisseria meningitidis, E. coli or Haemophilus influenzae  Because half of the patients develop sepsis from strep pneumoniae, penicillin can be administered immediately with onset of a febrile URI  Patients are instructed to obtain and wear a Medic alert tag

Hyposplenism  Is a potentially lethal syndrome characterized by diminished splenic function  The patient peripheral blood smears appear as if they are asplenic  Hyposplenism can occur in the presence of abnormal sized or enlarged spleen  The danger of hyposplenism is the risk of developing potentially lethal sepsis  Sickle cell anemia is the most common disease associated with hyposplenism  The most common surgical disease associated with hyposplenism is chronic UC

Hyposplenism

Overview  Definition of Hyposplenism  Medical History  The function of the spleen  Congenital asplenia vs. splenectomy  Immunological consequences of Hyposplenism  Diagnosis and complications

What is Hyposplenism?  Hyposplenism is the lack of a spleen or its function  The rare genetic disorder- Congenital Asplenia  The surgical removal of the spleen- splenectomy  Results in severe immunological consequences.

History  Immunological importance of the spleen  Morris and Bullock-1919  First post-splenectomy infection  O’Donnell-1929  Effects of Hyposplenism  King and Shumacker-1952

The Spleen  Largest lymphoid tissue of the body  Serves two main functions  Filters blood to remove damaged/old RBC- red pulp  Serves as secondary lymphoid tissue by removing infectious agents and using them to activate lymphocytes- white pulp  A significant reservoir for T lymphocytes  Plays an active role in the production of IgM antibodies and complement  Has significant role in the functional maturation of antibodies

Congenital Asplenia  Autosomal recessive genetic disorder  Believed to be caused by absence of the Hox 11 gene in the embryo  Causes decreased adaptive immune response  Associated with structural abnormalities in other organs of the body- cause death in infancy

Splenectomy  Removal of spleen tissue (partial or complete)  Usually needed because of trauma  Residual splenic function in ¼ to ⅔ of patients  IgM levels decreases, IgG levels remain constant or increase, IgA and IgE levels increase

Immunological Consequences  Causes slower and incomplete adaptive immune response against bacteria  Low levels of tuftsin, which stimulates phagocytosis by neutrophils, macrophages, and monocytes  Decreased neutrophil and macrophage activity  Increased NK cell activity  Limited capacity of circulating B-cells to differentiate into antibody-secreting cells  Decreased level of T-cells

Diagnosis  Determined by anatomic presence or absence of the organ, its size, and any lesions.  Function can be assessed by  Radiologic Techniques  X-ray, ultrasound, tomography, MRI, radionucleotide scanning  Morphologically  Peripheral blood smear- presence of Howell-Jolly bodies

Howell Jolly bodies Howell-Jolly bodies are round, purple staining nuclear fragments of DNA in the red blood cell

Complications  Lifelong risk for Overwhelming Postsplenectomy infection (OPSI)  Caused by Streptococcus pneumoniae and gram negative bacteria  Initial Symptoms: fever, chills, muscle aches, headache, vomiting, diarrhea, and abdominal pain  Progressive symptoms: bacteremic septic shock, extremity gangrene, convulsions, and coma  Mortality rate of 50-80%  from onset of initial symptoms, 68% of those deaths occur within 24 hours and 80% occur within 48 hours  Prevention: routine vaccinations and prophylactic antibiotics

Summary  Hyposplenism is the lack of a spleen or its function  Can be either genetic or surgically induced  It has detrimental effects on the immune system by decreasing the body’s ability to fight bacterial infections and reducing the adaptive immune response

Infections in Asplenic Patients

Causes of Asplenia  Congenital  Often associated with serious organ malformations  Acquired  Post surgical removal  Functional hyposplenism

Function of the Spleen  Immunological functions  Main site of opsonic antibody production  Especially efficient in removal of encapsulated bacteria  Remaining RES may compensate but not in case of encapsulated bacteria  Filtration  Removal of abnormal erythrocytes and intraerythrocytic inclusions eg nuclear inclusions and parasitised RBC

Overwhelming Infection  Overall incidence of sepsis is low  3,2% in adults  3,3% in children  Risk stratified according to cause, being highest in patients with thalassaemia major and sickle-cell anaemia (J Infect 2001 Oct;43: 182-6)  Lifetime risk for OPSI of 5%  Mortality  Death rates 600 times greater than general population  Higher in children (1,7% vs 1,3%), but other reports say higher in > 16 years  Mandel say doesn’t correspond to indication but Bisharat et al suggest higher in haematological disorders

Duration of risk  Most occur within 2 years post splenectomy  Risk is lifelong as cases have been reported up to 20 years post surgery  Early complications may be underreported as surgical complication

Microbiology  S. pneumonia  50 – 90% of cases  Common in all age groups  Distribution of serotypes seems to be same as other forms of pneumococcal infection  75% belonged to serotypes covered in 23 valent vaccine (ibid)

Micro cont…  H. influenza  Regarded as 2 nd most common cause  Incidence reduced with vaccination  Non-typable strains do not seem to predominate in PSS  N. meningitidis  Reported by some studies as associated but others as well as animal experiments seem to support a lack of association

Other Micro-organisms  Listeria monocytogenes  E. coli  Klebsiella sp  Salmonella typhimurium  S. aureus  Cytocapnophagia canimorsus  Plesiomonas shigelloides  Recently occupational exposures have been highlighted

Management  Immunisations  Pneumococcal – 2 weeks prior to elective surgery otherwise when patient is recovered prior to discharge. Boosters every 5-10 years  H. influenza – recommended but evidence for immunogenicity and boosters lacking  Meningococcal – not routinely recommended  Influenza – may be of value especially in reducing risk of secondary bacterial infection

Mx continued…  Antibiotic prophylaxis  Controversial  Penicillin  In all cases, esp in first 2 years post surgery  All up to 16 and if underlying immune dysfunction  May not prevent sepsis  Local resistence patterns need to accounted for  Home antibiotic supply

Cont………  Travellers  MALARIA PROPHYLAXIS  Meningococcal vaccine  Antibiotic prophylaxis  Education  Medic alert bracelet etc.