Anal squamous cell cancer is believed to be directly linked to the presence of a complex inflammatory process most commonly caused by HPV infection (particularly with serotypes 16 and 18) in the histologically unique area of the anal squamocolumnar epithelium. In one Scandinavian study, serotype 16 HPV DNA was detected in 73% of anal cancer specimens, and serotype 16, 18, or both were detected in 84% of specimens. In contrast, no rectal cancer specimens contained HPV DNA.

Tetany: A condition that is due usually to low blood calcium (hypocalcaemia) and is characterized by spasms of the hands and feet, cramps, spasm of the voice box (larynx), and overactive neurological reflexes. Tetany is generally considered to result from very low calcium levels in the blood. However, tetany can also result from reduction in the ionized fraction of plasma calcium without marked hypocalcaemia, as is the case in severe alkalosis (when the blood is highly alkaline).

Hypocalcaemic tetany (HT) is the consequence of severely lowered calcium levels (<2.0 mmol/l), usually in patients with chronic hypocalcaemia. The causal disease for hypocalcaemic tetany is frequently a lack of parathyroid hormone (PTH), (e. g. as a complication of thyroid surgery) or, rarely, resistance to PTH. HT due to severe and painful clinical symptoms requires rapid i. v. calcium replacement by central venous catheter on an intensive care unit.

The costomediastinal recess is the point where the costal pleura becomes the mediastinal pleura, located right next to the cardiac notch.
The cupola: part of the parietal pleura that extends above the first rib to the root of the lung.
Hilum: located on the medial surface of the lung where neurovascular structures enter and leave the lung.
Pulmonary ligament: pleural fold found below the root of the lung, is a point of continuity between the visceral and mediastinal pleura.
Costodiaphragmatic recess: the lowest extent of the pleural cavity.
Superior mediastinum: part of the mediastinum that contains the great vessels leaving and entering the heart.
The cardiac notch is in the inferior mediastinum.

Thrombomodulin is a protein cofactor expressed on the surface of endothelial cells. Thrombomodulin binds with thrombin forming a complex which activates protein C, initiating the anticoagulant pathway.

Familial adenomatous polyposis (FAP) is an autosomal dominant, hereditary colon cancer syndrome that is characterized by the presence of innumerable adenomatous polyps in the colon and rectum. Gardner’s syndrome is a variant of FAP, which in addition to the colonic polyps, also presents extracolonic manifestations, including desmoid tumours, osteomas, epidermoid cysts, various soft tissue tumours, and a predisposition to the thyroid and periampullary cancers.
Of patients with FAP, 75%-80% have a family history of polyps and/or colorectal cancer at age 40 years or younger.
Mutations of the APC gene are thought to be responsible for the development of FAP, and the location of the mutation on the gene is thought to influence the nature of the extracolonic manifestations that a given patient might develop.
Though patients are often asymptomatic, bleeding, diarrhoea, abdominal pain and mucous discharge frequently occur. Diagnostic tools include genetic testing, endoscopy, and monitoring for extra-intestinal manifestations.
If left untreated, all patients with this syndrome will develop colon cancer by age 35-40 years. Besides, an increased risk exists for the development of other malignancies.
Currently, surgery is the only effective means of preventing progression to colorectal carcinoma. Restorative proctocolectomy with ileal pouch-anal anastomosis (RPC/IPAA) with mucosectomy is the preferred surgical procedure since it attempts to eliminate all colorectal mucosa without the need for an ostomy. Periampullary carcinoma and intra-abdominal desmoid tumours are a significant cause of morbidity and mortality in these patients after colectomy. Frequent endoscopy is needed to prevent the former, while there is no definitive treatment available yet for the latter.

Answer: Flail chest injury

Flail chest is a life-threatening medical condition that occurs when a segment of the rib cage breaks due to trauma and becomes detached from the rest of the chest wall. Two of the symptoms of flail chest are chest pain and shortness of breath.

It occurs when multiple adjacent ribs are broken in multiple places, separating a segment, so a part of the chest wall moves independently. The number of ribs that must be broken varies by differing definitions: some sources say at least two adjacent ribs are broken in at least two places, some require three or more ribs in two or more places. The flail segment moves in the opposite direction to the rest of the chest wall: because of the ambient pressure in comparison to the pressure inside the lungs, it goes in while the rest of the chest is moving out, and vice versa. This so-called paradoxical breathing is painful and increases the work involved in breathing.

Flail chest is usually accompanied by a pulmonary contusion, a bruise of the lung tissue that can interfere with blood oxygenation. Often, it is the contusion, not the flail segment, that is the main cause of respiratory problems in people with both injuries.

Surgery to fix the fractures appears to result in better outcomes.

Complications of intravenous drug abuse, such as subcutaneous abscess, joint infections, osteomyelitis, overdose, hepatitis, and infective endocarditis, account for an increasing number of admissions in accident and emergency departments throughout the UK. The organisms that usually cause chronic osteomyelitis in intravenous drug users are Gram‐negative rods such as Pseudomonas aeruginosa and Gram‐positive cocci such as staphylococci. Early treatment is essential to prevent progressive bone destruction. TB tends to affect the thoracic spine and in other causes of osteomyelitis the lumbar spine is affected.

Gaining venous access in small children is challenging most of the times especially in cases of trauma. Therefore, intraosseous infusions should be preferred in this setting. Broviac lines are long-term IV access systems with narrow lumens and, hence, would be unsuitable.

Intraosseous access is typically undertaken at the anteromedial aspect of the proximal tibia and provides access to the marrow cavity and circulatory system. Although traditionally preferred in paediatric practice, it may be used in adults as well, and a wide range of fluids can be infused using this approach.

Healing can be sped-up or slowed down due to various reasons: 1. blood supply, 2. infection, 3. denervation, 4. collection of blood/hematoma, 5. mechanical stress, 6. foreign body, 7. techniques used during surgery and 8. dressing of the wound. Other systemic factors include 1. nutrition e.g. deficiency of zinc, vitamin C, protein deficiency, 2. metabolic status, 3. circulatory status and 4. hormonal influence

Inflammation is the immediate response of the body towards infections or irritations. The cardinal signs of inflammation are 1. redness/rubor, 2. tumour/swelling, 3.dolar/pain, 4.calor/heat and organ dysfunction (function laesa). Inflammation has 2 components; vascular and cellular. Blood vessels dilate upstream of the inflamed area leading to the rubor and calor and constrict downstream, increasing pressure and causing fluid to leak out of the capillary, resulting in swelling. The cellular component includes infiltration by neutrophils. Leukocyte arrival and functions include; 1. margination: cells marginated from the centre to the periphery of the vessel, 2. rolling: selectins are upregulated on the vessel walls, 3. adhesion: upregulation of the adhesion molecules ICAM and VCAM on the endothelium interact with integrins on the leukocytes resulting in adhesion, 4. diapedesis and chemotaxis: diapedesis is the transmigration of the leukocyte across the endothelium of the capillary and towards a chemotactic product and 5. phagocytosis: engulfing the offending substance/cell.

Answer: Epstein-Barr virus

The Epstein–Barr virus is one of eight known human herpesvirus types in the herpes family, and is one of the most common viruses in humans. Infection with Epstein-Barr virus (EBV) is common and usually occurs in childhood or early adulthood.
EBV is the cause of infectious mononucleosis, an illness associated with symptoms and signs like:
fever,
fatigue,
swollen tonsils,
headache, and
sweats,
sore throat,
swollen lymph nodes in the neck, and
sometimes an enlarged spleen.

Although EBV can cause mononucleosis, not everyone infected with the virus will get mononucleosis. White blood cells called B cells are the primary targets of EBV infection.
Petechiae on the palate are characteristic of streptococcal pharyngitis but also can be seen in Epstein–Barr virus infection, Arcanobacterium haemolyticum pharyngitis, rubella, roseola, viral haemorrhagic fevers, thrombocytopenia, and palatal trauma.
Despite the fact that infectious mononucleosis is a self-limiting disease, it may cause serious and lethal complications. The mechanism of splenic rupture secondary to infectious mononucleosis has been controversial. It is commonly believed that it is caused by an increase in intra-abdominal pressure or contraction of the diaphragm with vigorous cough, vomiting and defecation, leading to a compression of the spleen. However, Patel et al. argue that it is primarily the result of an expanding subcapsular haematoma which subsequently tears the capsule and leads to hemoperitoneum. Traditionally, rupture of spleen is treated by splenectomy. The rationale is to prevent the chance of sudden death as an early complication of splenic rupture and the risk from blood transfusion.

A below-knee amputation (“BKA”) is a transtibial amputation that involves removing the foot, ankle joint, and distal tibia and fibula with related soft tissue structures. In general, a BKA is preferred over an above-knee amputation (AKA), as the former has better rehabilitation and functional outcomes. There are three major categories of indications for proceeding with a BKA. These include:
– Urgent cases where source control of necrotizing infections or haemorrhagic injuries outweighs limb preservation.
– Less acutely, urgent BKAs may be performed for chronic nonhealing ulcers or significant infections with the risk of impending systemic infection or sepsis.
– Urgent BKAs may be performed where limb salvage has failed to preserve a mangled lower extremity. Adequate resuscitation and stabilization must always have occurred before such a decision, as judged by vital signs, lactate, base deficit, and the management of concomitant injuries.
This man is hemodynamically unstable and the limb is likely to be non-viable after so many hours of entrapment. Hence, the safest option would be primary amputation of the injured limb.

Signs and symptoms of thalamic syndrome include contralateral hemi anaesthesia, burning or aching sensation in one half of a body (hyperaesthesia), often accompanied by mood swings.

COPD leads to respiratory acidosis (chronic). This occurs due to hypoventilation which involves multiple causes, such as poor responsiveness to hypoxia and hypercapnia, increased ventilation/perfusion mismatch leading to increased dead space ventilation and decreased diaphragm function.

Overproduction of aldosterone (a mineralocorticoid) by the adrenal glands is known as Conn’s syndrome. It can be either due to an aldosterone-secreting adrenal adenoma (50-60% cases) or adrenal gland hyperplasia (40-50% cases). Excess aldosterone leads to sodium and water retention, along with potassium excretion. This leads to arterial (non-essential) hypertension. Conn’s syndrome is the commonest cause of primary hyperaldosteronism. Other symptoms include muscle cramps, headache (due to hypokalaemia) and metabolic alkalosis, which occurs due to increased secretion of H+ ions by the kidney. The raised pH of the blood traps calcium leading to symptoms of hypocalcaemia, which can be mimicked by liquorice ingestion and Liddle syndrome. To diagnose Conn’s syndrome, the ratio of renin and aldosterone is measured. Due to suppression of renin secretion, there is low renin to aldosterone ratio (<0.05). However, anti-hypertensives may affect the test results and should be withdrawn for 6 weeks. Computed tomography can also be done to detect the presence of adrenal adenoma.
Cushing’s syndrome does not cause hypokalaemia with normal serum glucose levels. Nelson’s syndrome refers to increased ACTH secretion due to pituitary adenoma. Pheochromocytoma will not lead to hypokalaemia even though hypertension can be seen.

The child has VACTERL
Over 50% of infants with oesophageal atresia have one or more additional anomalies.
The VATER association consists of a combination of anomalies including vertebral, anorectal, tracheooesophageal and renal or radial abnormalities. This association was later expanded as the VACTERL association to include cardiac and limb defects.
Other associations which may include oesophageal atresia are the CHARGE association (coloboma, heart defects, atresia choanal, retarded growth and development, genital hypoplasia and ear deformities), POTTER’S syndrome (renal agenesis, pulmonary hypoplasia, typical dysmorphic facies) and SCHISIS association (omphalocele, cleft lip and/or palate, genital hypoplasia). Genetic defects associated with oesophageal atresia include Trisomy 21 and 18, and 13q deletion. Of the cardiac anomalies, the most common are ventricular septal defect and tetralogy of Fallot. Major cardiac malformations are one of the main causes of mortality in infants with oesophageal atresia.

Embryologically the testes are retroperitoneal structures in the posterior abdominal wall, attached to the anterolateral abdominal wall by the gubernaculum. The gubernaculum ‘pulls’ the testes through the deep inguinal ring, inguinal canal and superficial inguinal ring and over the pelvic brim. The gubernaculum is preceded by the processus vaginalis that is derived from the peritoneum anterior to the testes. The processus vaginalis pushes the muscle and fascial layers. These eventually make up the canal and the spermatic cord, into the scrotum. The gubernaculum persists as the scrotal ligament while part of the processus vaginalis remains as a bursa-like sac i.e. the tunica vaginalis testes. The testes therefore could be caught in any one of these places along its path of descending. The testes are never in the perineum.

Answer: Curling’s ulcers

Curling’s ulcer is an acute gastric erosion resulting as a complication from severe burns when reduced plasma volume leads to ischemia and cell necrosis (sloughing) of the gastric mucosa. The most common mode of presentation of stress ulcer is the onset of acute upper GI bleed like hematemesis or melena in a patient with the acute critical illness.

A similar condition involving elevated intracranial pressure is known as Cushing’s ulcer. Cushing’s ulcer is a gastro-duodenal ulcer produced by elevated intracranial pressure caused by an intracranial tumour, head injury or other space-occupying lesions. The ulcer, usually single and deep, may involve the oesophagus, stomach, and duodenum. Increased intracranial pressure may affect different areas of the hypothalamic nuclei or brainstem leading to overstimulation of the vagus nerve or paralysis of the sympathetic system. Both of these circumstances increase secretion of gastric acid and the likelihood of ulceration of gastro-duodenal mucosa.

Mallory-Weiss syndrome is characterized by upper gastrointestinal bleeding secondary to longitudinal mucosal lacerations (known as Mallory-Weiss tears) at the gastroesophageal junction or gastric cardia. However, Mallory-Weiss syndrome may occur after any event that provokes a sudden rise in the intragastric pressure or gastric prolapse into the oesophagus, including antecedent transoesophageal echocardiography. Precipitating factors include retching, vomiting, straining, hiccupping, coughing, primal scream therapy, blunt abdominal trauma, and cardiopulmonary resuscitation. In a few cases, no apparent precipitating factor can be identified. One study reported that 25% of patients had no identifiable risk factors.

The steps involved in leukocyte arrival and function are:
1. margination: cells migrate from the centre to the periphery of the vessel
2. rolling: selectins are upregulated on the vessel walls
3. adhesion: upregulation of the adhesion molecules ICAM and VCAM on the endothelium interact with integrins on the leukocytes, interaction of these results in adhesion
4. diapedesis and chemotaxis: diapedesis is the transmigration of the leukocyte across the endothelium of the capillary and towards a chemotactic product
5. phagocytosis: engulfing the offending substance/cell.

The bronchial circulation is part of the systemic circulation and receives about 2% of the cardiac output from the left heart. Bronchial arteries arise from branches of the aorta, intercostal, subclavian or internal mammary arteries. The bronchial arteries supply the tracheobronchial tree with both nutrients and O2. It is complementary to the pulmonary circulation that brings deoxygenated blood to the lungs and carries oxygenated blood away from them in order to oxygenate the rest of the body.

CLL or chronic lymphocytic leukaemia is the most common leukaemia seen in the Western world. Twice more common in men than women, the incidence of CLL increases with age. About 75% cases are seen in patients aged more than 60 years. The blood, marrow, spleen and lymph nodes all undergo infiltration, eventually leading to haematopoiesis (anaemia, neutropenia, thrombocytopenia), hepatomegaly, splenomegaly and decreased production of immunoglobulin. In 98% cases, CD+5 B cells undergo malignant transformation.
Often diagnosed on blood tests while being evaluated for lymphadenopathy, CLL causes symptoms like fatigue, anorexia, weight loss, pallor, dyspnoea on exertion, abdominal fullness or distension. Findings include multiple lymphadenopathy with minimal-to- moderate hepatomegaly and splenomegaly. Increased susceptibility to infections is seen. Herpes Zoster is common. Diffuse or maculopapular skin infiltration can also be seen in T-cell CLL.
Diagnosis is by examination of peripheral blood smear and marrow: hallmark being a sustained, absolute leucocytosis (>5 ×109/l) and increased lymphocytes in the marrow (>30%). Other findings can include hypogammaglobulinemia (<15% of cases) and, rarely, raised lactate dehydrogenase (LDH). Only 10% cases demonstrate moderate anaemia and/or thrombocytopenia.

The pathogenicity of an organism or its ability to cause disease is determined by its virulence factors. Many bacteria produce virulence factors that inhibit the host’s immune system. The virulence factors of bacteria are typically proteins or other molecules that are synthesized by enzymes. These proteins are coded for by genes in chromosomal DNA, bacteriophage DNA or plasmids. The proteins made by the bacteria can poison the host cells and cause tissue damage.

Achalasia is a failure of the lower oesophageal sphincter (LES) to relax that is caused by the degeneration of inhibitory neurons within the oesophageal wall. It is classified as either primary (idiopathic) or secondary (in the context of another disease). In patients with achalasia, the chief complaint is dysphagia to both solids and liquids, although regurgitation, retrosternal pain, and weight loss may also occur. Upper endoscopy, barium esophagram, and oesophageal manometry play complementary roles in the diagnosis of achalasia. While upper endoscopy and/or barium esophagram are often obtained initially, manometry usually confirms the diagnosis, and upper endoscopy is indicated to rule out a malignant underlying cause. In good surgical candidates, achalasia is usually treated with pneumatic dilation or myotomy. In most other cases, an injection of botulinum toxin is attempted. If these measures fail to provide relief, medical therapy (e.g., nifedipine) is indicated.

Necrosis and ulcers of the colon are a feature of infection with enteroinvasive E. coli (EIEC). It presents with a dysentery-type illness similar to shigellosis.

E. coli have different strains that cause a wide range of conditions. The four main types are:

1. Enteropathogenic E. coli—cause watery diarrhoea, vomiting, and low-grade fever

2. Enteroinvasive E. coli—cause dysentery, large bowel necrosis, and ulcers

3. Enterotoxigenic E. coli—cause traveller’s diarrhoea

4. Enterohaemorrhagic E. coli 0157:H7—cause haemorrhagic colitis, haemolytic uremic syndrome, and thrombotic thrombocytopenic purpura

A stretch reflex is a monosynaptic reflex that causes muscle contraction in response to stretching within that muscle. The sensory apparatus in a muscle that are sensitive to stretch are the muscle spindles. The patellar (knee jerk) reflex is an example. In upper motor neuron lesions, the stretch reflexes tend to be brisk due to loss of inhibitory signals on gamma neurons through the lateral reticulospinal tract.

Liposarcoma is a cancer that arises in fat cells in deep soft tissue. Commonly it occurs inside the thigh or retroperitoneum. It usually affects middle-aged and older adults, over 40 years. Liposarcoma is the most common soft-tissue sarcoma. It is very radio resistant. Five-year survival rates vary from 100% to 56% based on histological subtype.

In atrial fibrillation, the abnormal atrial contraction can cause blood to stagnate in the left atrium and form a thrombus, which may then embolize. The patient’s history of AF suggest an embolic disease, which lead to his death.

The pterygomandibular raphé (pterygomandibular ligament) provides attachment on its posterior border to the superior pharyngeal constrictor and on its anterior border to the buccinator muscle.

Angio-oedema, is the rapid swelling of the skin, mucosa and submucosal tissues. The underlying mechanism typically involves histamine or bradykinin. The version related to histamine is to due an allergic reaction to agents such as insect bites, food, or medications. The version related to bradykinin may occur due to an inherited C1 esterase inhibitor deficiency, medications e.g. angiotensin converting enzyme inhibitors, or a lymphoproliferative disorder.

The tuberosity of the tibia is the site of attachment to the ligamentum patella (the tendon of the quadriceps femoris muscle which include four heads: rectus femoris, vastus medialis, intermedius and lateralis).