Appendicitis: A Vestigial Remnant to Belly Pain

The appendix is a small out-pouching off a part of the large intestine known as the cecum. It functions similar to normal large intestine by secreting mucous and absorbing water. Its overall importance, however, is not well understood, and it is likely a vestigial remnant from a distant ancestor. Unfortunately for some unlucky folk it can become inflamed; when this occurs it is called “appendicitis”.

Appendicitis occurs when something blocks the opening of the appendix into the cecum. There are numerous causes. The most common in younger individuals is a mass of inflammatory cells known as lymphoid hyperplasia, which can occur after a viral or bacterial infection of the gut. In older individuals, the most common cause is a small, hard piece of poop known as a “fecalith”.

When lymphoid hyperplasia or a fecalith (or any other obstructing thing) blocks the opening of the appendix, any mucous secreted by it gets trapped. When the appendix becomes distended enough, it literally chokes off its own blood supply and starts to die.

The dying appendix sets off a cascade of inflammation. Bacteria within the intestine are able to move in and wreak further havoc! The end result is a nasty inflammatory process, that if left unchecked, can lead to a very serious surgical illness.

Signs and Symptoms

Appendicitis initially presents with periumbilical pain (ie: pain around the belly button) that quickly migrates to involve the right lower quadrant of the abdomen.

The reason pain occurs in this sequence is because the initial discomfort of appendicitis is due to inflammation of the visceral peritoneum and appendix itself. The visceral peritoneum is a layer of tissue that envelopes the gut tube. This type of pain is carried back to the spinal cord by autonomic nerves, and due to their embryological origin, that pain gets referred to the midline of the abdomen (the belly button).

Over the course of the disease, the parietal peritoneum eventually becomes inflamed. This pain is carried by somatosensory nerves with a very specific dermatomal distribution, thus the pain gets localized directly to the anatomical location of the appendix – the right lower quadrant. This pain is often very well localized at an area known as McBurney’s point.

Patients often have nausea, vomiting, and a decreased appetite. In fact, if patients are hungry and want to eat, appendicitis becomes a highly unlikely diagnosis for abdominal pain. This is referred to informally as the "cheeseburger sign".

There are also several physical exam findings. Pain with palpation of the right lower quadrant associated with rebound tenderness (ie: pain that occurs when you release pressure during palpation) is frequently seen. Sometimes palpating the left lower quadrant (ie: the area on the other side of the abdomen from the appendix) will cause discomfort in the right lower quadrant. This is known as "Rovsing’s sign".

Any maneuvers that irritate the peritoneum will also cause discomfort. The first of these signs occurs when you flex the hip. This causes the iliopsoas muscle to rub up against an inflamed peritoneum. This is known as the "psoas sign". Another way to irritate the peritoneum is to internally rotate the leg while the patient’s knee and hip are flexed. This is known as the "obturator sign".


Appendicitis CT Scan
Appendicitis is first and foremost a clinical diagnosis. Therefore, in patients with a history of periumbilical pain that migrates to the right lower quadrant appendicitis is the most likely diagnosis.

However, in a world with advanced imaging technologies we can quickly get pictures that support the diagnosis. Both ultrasound (frequently used in children, pregnant patients, and younger adults) or CT scans can be obtained quickly and inexpensively. The CT scan will show fat stranding and fluid around an enlarged appendix (see image to the left).

Blood tests such as a complete blood count (CBC) will show an elevated white blood cell count (ie: the cells that fight off infection and are responsible for inflammation).


Treatment is surgical (ie: appendectomy)! Get that nasty inflamed appendix out of there STAT! In addition, patients are started on intravenous fluids and antibiotics that cover anaerobic organisms.

Commonly used antibiotics for a non-ruptured appendix are metronidazole, ampicillin/sulbactam, and ciprofloxacin. If the appendix has ruptured, broad spectrum coverage with piperacillin/tazobactam or a combination of ampicillin, ciprofloxacin, and clindamycin is started and continued for at least 5 days.

Occasionally a ruptured appendix will wall itself off into an abscess. If this is the case, the abscess must be drained with a needle. Antibiotics are started, and the patient is taken to surgery roughly six weeks later to remove the appendix after the inflammation has "calmed down".


Appendicitis occurs when something blocks the opening of the appendix into the cecum. Progressive enlargement of the appendix occurs eventually chocking off its own blood supply. Pain in the right lower quadrant of the abdomen is a common symptom of appendicitis. Diagnosis is clinical, but ultrasound and CT scanning can be helpful in elucidating unclear cases. Treatment is appendectomy (removal of the appendix), IV fluids, and antibiotics.

References and Resources

  • Merlin MA, Shah CN, Shiroff AM. Evidence-based appendicitis: the initial work-up. Postgrad Med. 2010 May;122(3):189-95.
  • Kim JK, Ryoo S, Oh HK, et al. Management of appendicitis presenting with abscess or mass. J Korean Soc Coloproctology. 2010 Dec;26(6):413-9. Epub 2010 Dec 31.
  • Lee SL, Islam S, Cassidy LD. Antibiotics and appendicitis in the pediatric population: an American Pediatric Surgical Association Outcomes and Clinical Trials Committee systematic review. J Pediatr Surg. 2010 Nov;45(11):2181-5.
  • Markides G, Subar D, Riyad K. Laparoscopic versus open appendectomy in adults with complicated appendicitis: systematic review and meta-analysis. World J Surg. 2010 Sep;34(9):2026-40.
  • Grundmann RT, Petersen M, Lippert H, et al. The acute (surgical) abdomen – epidemiology, diagnosis and general principles of management. Z Gastroenterol. 2010 Jun;48(6):696-706. Epub 2010 Jun 1.

Hodgkin’s Lymphoma: B-Cells, Pel-Ebstein, and EBV

Lymphoma is a cancer that develops from cells in the body known as lymphocytes. Lymphocytes are a subcategory of white blood cells, which are the cells that help ward off infection. There are two different types of lymphocytes: B-cells and T-cells. The majority of lymphomas, including Hodgkin’s disease, stem from B-cells.

In Hodgkin’s disease a B-cell, for unknown reasons, becomes cancerous. The cell then makes many clones of itself. These cells bundle together to form a solid tumor known as a lymphoma.

Why B-cells in Hodgkin’s lymphoma become cancerous is not entirely known. One belief is that infection with Epstein-Barr virus (the same virus that causes infectious mononucleosis) can cause the cells to turn cancerous in genetically susceptible people. Other theories are that certain genetic translocations may be the underlying factor. As of yet, no particular theory has significant supporting data to call it the true cause. It is likely that the development of Hodgkin’s disease is multi-factorial.


Reed-Sternberg Cell

There are different types of Hodgkin’s lymphoma. They are based on unique histopathological (ie: what it looks like under a microscope) characteristics, and are important in determining prognosis.

The histopathological features the pathologist looks for are the number of Reed-Sternberg cells, as well as the number of lymphocytes present in the biopsy specimen. A Reed-Sternberg cell is a funny shaped cell with two nuclei that looks like an "owl’s eyes" (see image to the right). They are believed to form when two cells merge together under the influence of certain proteins produced by the Epstein-Barr virus.

The first category, and most common type, is nodular sclerosing Hodgkin’s lymphoma. In this type, there are very few Reed-Sternberg cells with a moderate number of lymphocytes. It commonly occurs in younger individuals, and with treatment, the prognosis is excellent.

The second category is mixed cellularity Hodgkin’s lymphoma. This type has many Reed-Sternberg cells, and a moderate number of lymphocytes when viewed under the microscope. It has an intermediate prognosis.

The third category is lymphocyte predominant Hodgkin’s. It has very few Reed-Sternberg cells and many lymphocytes. It occurs most commonly in males less than 35 years of age. It is also one of the few types that is not associated with Epstein-Barr virus infection.

The last category is lymphocyte depleted. It is the rarest form of Hodgkin’s lymphoma. It typically affects older males.

Hodgkin's Types
Unfortunately it has the worst prognosis of the four types types.

The image to the left is one way of organizing the different Hodgkin’s types and their prognosis based on age, number of RS cells, and prognosis. LP = lymphocyte predominant, NS = nodular sclerosing, MC = mixed cellularity, LD = lymphocyte depleted.

Signs and Symptoms

The classic presentation of Hodgkin’s lymphoma is painless enlargement of the lymph nodes. This is similar to non-Hodgkin’s lymphoma, and the only way to differentiate the two is through biopsy.

Systemic manifestations may occur and include night sweats, fever, and weight loss. However, these are more common in patients with disseminated (ie: metastatic) disease. Interestingly, a pathognomonic (ie: seen exclusively in Hodgkin’s lymphoma) feature that occurs in some cases is pain of the involved nodes after drinking alcohol. Finally, a symptom known as Pel-Ebstein fevers are also specific for the disease. A Pel-Ebstein fever is a cyclical fever that occurs for several weeks at a time followed by a fever free period.

Other signs related to the immune system can be seen in patients with Hodgkin’s lymphoma. A condition known as cutaneous anergy can occur. Anergy refers to a lack of response by the cell mediated immune system. For example, in patients with tuberculosis a reaction will occur underneath the skin when they get a TB test. This reaction is the result of their cell mediated immunity reacting to the tuberculosis components injected underneath the skin. However, in anergic patients no reaction is seen, even if they have tuberculosis! This can also occur in patients with Hodgkin’s disease.


Hodgkin's Disease PET-CT
Diagnosis of Hodgkin’s lymphoma is made by looking at a biopsy specimen underneath the microscope. The most common way of obtaining a specimen is through biopsy of a lymph node. Differentiating Hodgkin’s from other types of lymphomas is important because it determines the best treatment options.

Additional studies are often performed to determine the number and location of involved lymph nodes. One such study is a positron emission tomograph (PET) combined with a CT scan. Any lymph nodes involved "light up" on the scan. An example, with the arrows pointing to involved nodes, is shown to the right.


Staging of Hodgkin’s lymphoma was traditionally based on a system known as the Ann Arbor Classification. It is divided into four stages. In stage 1 disease a single lymph node, or single organ is involved. In stage 2 disease involvement of multiple (two or more) lymph node regions on the same side of the diaphragm is present. In stage 3 disease involvement of nodes on both sides of the diaphragm is present; the spleen or other limited organ involvement may also be present. In stage 4 disease multiple organs are involved; interestingly, lymph node involvement is not necessary for a stage 4 diagnosis, although it is commonly present. Finally, each stage is further divided into “A” and “B” depending on whether or not symptoms are present. If symptoms are present, the stage is upgraded to a “B”.

Ann Arbor Classification (simplified)
Stage 1 Single lymph node or organ
Stage 2 Multiple lymph nodes on same side of diaphragm
Stage 3 Lymph nodes on both sides of diaphragm
Stage 4 Multiple organs involved

However, more recently the Lugano staging classification has become the preferred method. It divides disease into limited and advanced. Limited disease includes stage 1 and stage 2. Stage 1 involves a single lymph node or nearby nodes. Stage 2 involves two or more nodal groups. Advanced disease includes stages 3 and 4. In stage 3 disease nodes on both sides of the diaphragm are involved as is the spleen. Stage 4 disease is disseminated disease into organs. There are sub-categories in the Lugano model as well.


Like most cancers treatment is highly dependent on the stage of the disease. In most cases chemotherapy and radiation are used. Radiation is directed at involved lymph nodes, as well as lymph nodes that are uninvolved, but nearby. Common chemotherapeutic agents used include: adriamycin, bleomycin, vinblastine, vincristine, prednisone, procarbazine, and mechlorethamine.


Hodgkin’s lymphoma is a cancer of a type of white blood cell known as a B-cell. There are numerous categories depending on its histopathological characteristics. Patients often have painless enlarged lymph nodes. Some patients have fever, weight loss, and other non-specific symptoms. Staging is based on the Ann-Arbor model. Treatment usually involves a combination of chemotherapy and radiation.

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References and Resources