BDS2-important lectures

Leukaemias

• Leukaemias are malignant neoplasms of haemopoietic stem cells
• Leukaemias result in:
  • Diffuse replacement of bone marrow and normal blood precursor cells by neoplastic cells
  • Bone marrow failure, leading to anaemia, neutropenia, and thrombocytopenia
  • Leukaemic cells spilling over into blood and infiltrating organs
• Leukaemias can be classified into two cell lines:
  • Myeloid (resulting in basophils, neutrophils, eosinophils, monocytes, and macrophages)
  • Lymphoid (resulting in B, T cells, and plasma cells)
• Leukaemias can be classified into two types of maturity:
  • Acute (more than 50% myeloblasts or lymphoblasts in bone marrow at clinical presentation)
  • Chronic (more differentiated cells)

Diagnosis of Leukaemia

• Blood film and bone marrow analysis are important prognostic indicators, helping to identify:
  • Leukaemia type
  • Cell phenotype
  • Chromosomal abnormalities

Aetiology of Leukaemia

• Leukaemia can be caused by:
  • Ionising radiation
  • Chemicals (e.g., benzene and alkylating agents)
  • Viruses (e.g., HTLV - human T-cell leukaemic virus)
  • Genetic factors (e.g., Down's syndrome)
  • Acquired haematological disorders (e.g., aplastic anaemia)

Clinical Features of Leukaemia

• Marrow infiltration causes:
  • Pallor
  • Malaise
  • Fever and infections due to the effect on the immune system
  • Bleeding due to the impact on coagulation
  • Bruising/petechiae
• Tissue infiltration causes:
  • Lymphadenopathy
  • Hepatosplenomegaly
  • Central nervous system involvement
  • Bone and joint pain (acute lymphoblastic leukaemia, ALL)
  • Testicular involvement (ALL)
  • Gingival hypertrophy (acute myeloid leukaemia, AML)

Types of Leukaemia

• AML (Acute Myeloid Leukaemia)
• ALL (Acute Lymphoblastic Leukaemia)
• CML (Chronic Myeloid Leukaemia)
• CLL (Chronic Lymphoblastic Leukaemia)

Management of Leukaemia

• AML:
  • Higher than 80% cure rate with intensive chemotherapy in young patients
  • 15% of patients have a disease resistant to chemo
  • Autologous and allogenic stem cell transplant used if chemo fails
• ALL:
  • More than 60% cure rate with chemotherapy in 2-12-year-olds
  • 20% cure rate with chemotherapy in adults
  • Combination chemotherapy used to induce remission
  • CNS treatment performed prophylactically
  • Maintenance therapy for up to 2 years increases disease-free survival
• CLL:
  • Asymptomatic patients do not require treatment
  • 30% of patients with early-stage disease die of unrelated causes
  • Chemo typically effective
  • Median survival 10-12 years
  • Mortality usually due to infection or bone marrow failure
  • Bone marrow transplantation occasionally attempted in younger patients with poor prognostic disease

Lymphomas

• Hodgkin's Lymphoma:
  • Peak incidence in the 3rd decade
  • Aetiology unknown but EBV (infectious mononucleosis) suggested
  • Clinical features:
    • Lymphadenopathy
    • Constitutional 'B' symptoms
    • Anorexia and fatigue
    • Fever
    • Night sweats
    • Weight loss
    • Pruritus and erythematous rash
    • Mediastinal involvement
    • Hepatosplenomegaly
  • Staging:
    • Ann Arbor system
    • I - Single LN region
    • II - Two LN regions on the same side of the diaphragm
    • III - Groups on both sides of the diaphragm
    • IV - Widespread disease outside lymphatic sites
  • Treatment:
    • Early stage disease: Chemotherapy + radiotherapy
    • Advanced stage disease: Combination chemotherapy
    • Complete remission 60-90%
    • Prognosis relative to stage of disease
• Non-Hodgkin's Lymphoma:
  • Peak incidence increases with age
  • Aetiology:
    • Immunodeficiency
    • Infections
    • Ionising radiation
    • Carcinogenic chemicals
    • Inherited disorders affecting DNA damage and repair
  • Clinical features:
    • Generalised lymphadenopathy
    • Oropharyngeal involvement
    • Bone marrow infiltration
  • Treatment:
    • Low-grade disease: Asymptomatic patients require no treatment
    • High-grade disease: Combination chemotherapy
  • Management:
    • If asymptomatic, no treatment
    • Chemotherapy used if evidence of organ damage

Multiple Myeloma

• Peak incidence: 40-80 years old
• Aetiology:
  • Arises from malignant transformation of terminally differentiated B cell (plasma cell)
  • Results in secretion of Ig or light chains (paraproteins)
• Clinical features:
  • Typically long asymptomatic phase
  • Bone destruction
  • Bone marrow failure
  • Renal failure
  • Hyperviscosity syndrome
  • Amyloidosis
• Investigations:
  • FBC to detect bone marrow failure
  • Raised ESR and Ca2+
  • U&Es demonstrate renal damage
  • Protein electrophoresis demonstrates monoclal paraprotein
  • Bence-Jones proteins in urine
• Management:
  • Only treated if there is evidence of organ damage
  • Chemotherapy used if evidence of bone marrow failure or bone lesions
  • Most patients respond, but relapse is common
  • Radiotherapy is useful if there is bone pain### Dysphagia
• Difficulty in swallowing
• Symptoms: sticking sensation in the throat/chest during or after swallowing
• 9 oesophageal reasons for dysphagia:
  • Tumours (SCC and adenocarcinoma)
  • Inflammation (acid reflux, drugs, chemical burn)
  • Stricture (radiation, acid reflux)
  • Foreign body (soft food, impacted coins, bones)
  • Trauma (bony, surgical)
  • Webs (atrophic mucosa, fibrous stricture at upper end of oesophagus)
  • Goitre, enlarged left atrium, mediastinal glands
  • Oesophageal spasms
  • Achalasia (loss of ganglia, failure of relaxation of cardiac sphincter)

Oesophagus

• Musculo-tendinous tube connecting the pharynx to the stomach
• Symptoms:
  • Dysphagia
  • Pain (from acid reflux)
  • Cough or vomiting (foods/liquids refluxing into pharynx)
  • Bleeding (haematemesis)
• Diseases associated with oesophagus:
  • Pharyngeal pouch
  • Achalasia
  • Oesophageal spasm
  • Oesophageal web
  • Peptic ulcer disease/reflux
  • Carcinoma
• Composition of oesophagus:
  • Upper 2/3: striated muscle
  • Lower 2/3: non-striated muscle
  • Middle 1/3: mixed muscle
• Innervation: vagus nerve (X)
• Epithelium: stratified squamous non-keratinising epithelium

Swallowing

• Peristaltic wave triggered
• Food bolus pushed to stomach
• Gut stretches, causing depolarisation and action potential, propagating peristalsis

Pharyngeal Pouch

• Herniation of mucosa through weakness in pharyngeal constrictor muscles
• Symptoms:
  • Dysphagia
  • Vomiting
  • Respiratory symptoms
  • Zeneker's Diverticulum forms
• Treatment: dilatation of stricture, correction of iron deficiency, excision of web

Oesophagitis

• Inflammation of oesophagus due to acid reflux from the stomach
• Causes:
  • Acid reflux
  • Immunocompromised: transplant, chemo, HIV infection

Achalasia of the Cardia

• Loss of ganglia from intramural plexus, leading to failure of relaxation of cardiac sphincter
• Symptoms:
  • Dysphagia for solids and liquids
  • Eventual failure of peristalsis, leading to progressive dilatation of oesophagus
• Treatments:
  • Drugs (nifedipine to relax sphincter)
  • Balloon dilatation
  • Cardiomyotomy

Oesophageal Spasm

• Term for spasm due to various causes
• Causes:
  • Atypical achalasia
  • Gastro-oesophageal reflux
  • Motor disorders
  • Symptomatic peristalsis
  • Obstruction at cardia
  • Neuromuscular disorders
• Result: corkscrew oesophagus, pain, and reflux; treated with muscle relaxants

Peptic Ulcer Disease/Reflux

• Failure of upper (cardiac) sphincter
• Acid refluxing into oesophagus
• Symptoms:
  • Pain
  • Vomiting
  • Haematemesis (vomiting blood)
  • Ulcer with scarring
• Investigations:
  • Endoscopy
  • Barium meal
• Treatments:
  • Control predisposing factors (antacids)
  • Decrease secretions (H-2 blockers, proton pump inhibitors)
  • Treat H. pylori with quadruple therapy

Gastritis

• Inflammation of stomach lining
• Consequences:
  • Chronic inflammation and irritation
  • Reduced acid production
  • Iron deficiency (glossitis and microcytic anaemia)
  • Vitamin B12 deficiency (macrocytic anaemia and sore mouth)

Barrett's Oesophagus

• Long-standing reflux from stomach causing change in inflammation in lower oesophageal lining
• Risk factor for oesophageal carcinoma### Gastrointestinal System
• The small intestine consists of three components: Duodenum, Jejunum, and Ileum
• The large intestine consists of three components: Cecum, Rectum, and Anal canal

Coeliac Disease

• Dietary source: Gluten sensitivity (wheat, barley, rye, and oats)
• Genetic source: The HLA B8 tissue type
• Presentation: Change of bowel habit (COBH)
• Gastrointestinal symptoms:
  • Diarrhea
  • Flatulence
  • Borborygymus
  • Weight loss
  • Weakness, fatigue
  • Abdominal pain
  • Secondary lactose intolerance
  • Steatorrhea
• Extra-intestinal symptoms:
  • Anaemias (10-15%): Fe and B12 deficiencies
  • Neurological symptoms (8-14%)
  • Skin disorders (10-20%): Endocrine disturbances (infertility, impotence, amenorrhea, delayed menarche)
• Diagnosis:
  • Using antibodies to gliadin, endomysium, and transglutaminase (TTG)
  • Endoscopic biopsy
  • Pillcam camera for non-invasive inspection
• Treatment:
  • Gluten restriction (cures 95%)
  • Corticosteroids (for the remaining 5%)
• Risks:
  • Lymphoma and adenocarcinoma of the pancreas, oesophagus, small bowel, and biliary tract
  • T and B cell non-Hodgkin lymphoma

Malabsorption Problems

• Vitamin deficiencies:
  • B12, folate, and ferritin deficiency leading to glossitis, angular cheilitis, anaemia, burning mouth, and smooth tongue
  • Vitamin K deficiency leading to bleeding tendency
  • Vitamin D deficiency leading to osteomalacia and rickets in children
• Dental problems:
  • Enamel defects in the permanent dentition, such as hypoplasia, if the onset is in childhood

Inflammatory Bowel Diseases (IBDs)

• Types:
  • Crohn's disease
  • Ulcerative colitis
• Ulcerative colitis is more common than Crohn's disease
• Gender ratio:
  • Females: 1.2:1
  • Males: 1.2:1
• Age of onset:
  • Crohn's disease: 26 years old
  • Ulcerative colitis: 34 years old
• Immune aetiology: Defective immune systems, leading to autoimmunity
• Hygiene and prevalence:
  • Crohn's disease: occurs in good hygiene and developed countries
  • Ulcerative colitis: no relation to hygiene
• Protective factors:
  • Appendicectomy is protective of Ulcerative colitis
  • Breast feeding
• Differences in affected areas:
  • Crohn's disease: anywhere from mouth to anus
  • Ulcerative colitis: proximal from the rectum

Crohn's Disease

• Definition: A lifelong condition where parts of the digestive system become inflamed
• Symptoms:
  • Intermittent abdominal pain, diarrhea, abdominal distension
  • Decreased appetite
  • Anaemia and weight loss
  • Fresh blood or melaena
  • Fistulae and perianal sepsis
• Macroscopic changes:
  • Thickened bowel
  • Narrowed lumen
  • Deep ulcers
  • Mucosal fissures
  • Cobblestoning
  • Fistulae
  • Abscess
  • Aphthoid ulceration
• Microscopic changes:
  • Chronic inflammatory cells occur transmurally
  • Lymphoid hyperplasia
  • Granulomas occur in Langhan's cells
• Diagnosis:
  • Barium enema
  • Sigmoidoscopy, biopsy, and colonoscopy
  • Differential diagnosis includes TB and sarcoidosis
• Treatment:
  • Medical: glucocorticoids, immunomodulators, and biologics
  • Surgical: intestinal resection

Ulcerative Colitis

• Oral manifestations:
  • Aphthous ulcers
  • Tongue coating
  • Gingivitis
  • Periodontitis
  • Halitosis
  • Acidic taste
  • Cutaneous manifestations
• Treatment:
  • Aminosalicylates
  • Steroids
  • Azathioprine

Triggers and Treatment of IBDs

• Triggers:
  • Rashes
  • Mouth ulcers
  • Joint/back pain
  • Eye problems
  • Family history
  • Smoking status
• Bedside investigations:
  • Stool culture
  • Sigmoidoscopy
• Blood investigations:
  • Full blood counts
  • Haematemics
  • Inflammatory markers
  • Liver function tests
  • Blood cultures
  • Serological tests
• Imaging investigations:
  • Abdominal x-ray
  • Barium
  • CT scan
  • Chest x-ray
  • Ultrasound scan
• Treatment steps:
  1. Induce remission
  2. Maintain remission
  3. Biologics for Crohn's disease only

Cyclosporin and Dental Management

• In some patients, tenderness, swelling, or bleeding of the gums may appear soon after treatment with cyclosporine
• Brushing and flossing teeth carefully and regularly, and massaging gums may help prevent this
• Regular dental check-ups are necessary

Surgery and IBDs

• Acute indications for surgery in Ulcerative colitis:
  • Failure of medical treatment for 3 days
  • Toxic dilatation
  • Haemorrhage
  • Perforation
• Chronic indications for surgery in Ulcerative colitis:
  • Poor response to medical treatment
  • Excessive steroid use
  • Non-compliance with medication
  • Risk of cancer
• ICHOP acronym for surgery: Infection, Carcinoma, Haemorrhage, Obstruction, and Perforation

Prognosis and Colorectal Cancer

• Prognosis of Ulcerative colitis:
  • 1/3 single attack
  • 1/3 relapsing attacks
  • 1/3 progressively worsen requiring colectomy within 20 years
• Prognosis of Crohn's disease: Varied, new biological agents improving, so course of condition always changing
• Ulcerative colitis has an increased risk of colon cancer
• Predisposing factors for colon cancer:
  • Neoplastic polyps
  • Ulcerative colitis
  • Familial polyposis coli
  • Previous cancer
  • Crohn's disease