Objective 1: Recognize some causes for a solitary lung mass Pulmonary TB - Fig 14-10 pg332 This is the leading

g cause of death globally from a single infectious agent - mostly M. tuberculosis, though it can be from atypical mycobacteria like M. kansasii, M. avian intracellulare. Though about of the worlds population is said to have been infected by the organism, the disease only manifests in about 10% of cases with infection - sometimes the hosts resistance beats out the pathogenicity of the bacteria, and thus you dont get TB but TB is the main cause of HIV-related death in Africa and the Far East. Therapy: now drug therapy, that acts to kill the organism - using combination antibacterial chemotherapy - plus immunisation (BCG). Tx used to be special diets and bed rest! Clinicopathological features: extremely variable, depending on the extent, stage and activity of the disease symptoms: from insidious weight loss with night sweats, mild chronic cough to rampant bronchopneumonia with fever, dyspnoea, respiratory distress - the latter is galloping consumption. Most early cases of primary TB are clinically silent. Pre-disposing conditions: Immunosuppression (HIV/AIDS), alcoholism, DM Types of TB: primary: The tubercle bacilli meet the human for the first time iin the lungs, and the site of primary infection is called the Ghon focus. The pulmonary lesion has a central zone of caseous (necrotic cheese-like tissue) surrounded by palisaded (a row of elongated nuclei parallel to each other) epitheloid histiocytes, lympocytes and the ocassional Langhans giant cell. The lymph nodes that drain the affected part of the lung will have similiar granulomas. most of the time the primary lesion forms a fibrocalcific nodule with no clinical sequalae - but the bacilli can still live on in the foci, sometimes with the infection spreading systemically secondary: mostly happens when the primary infection reactivates. These lesions are nearly always in the lung apices, sometimes bilaterally. While most lesions are converted to fibrocalcific scars, they can lead to complications....histologically, you see granulomas with central zones of caseous necrosis. miliary: this can be a consequence of either primary or secondary TB where there is severe impairment of host resistance. disease becomes widely disseminated - you get numerous small granulomas in many organs, commonly in lungs, meninges, bone marrow and liver ACUTE MEDICAL EMERGENCY, w/o chemo its fatal Host resistance to TB and tuberculin (Mantoux/Heaf) test TB is a typical infective Type IV delayed hypersensitivity reaction killing mediated by T-lymphocytes and cytokines activating macrophages - this takes time, and sensitivty to tubercle bacilli is only detectable at 2-4 weeks after inoculation BCG is a vaccine made by non-virulent tubercle bacilli - the virulence and antigenicity is thought to be due to the lipid properties of the cell wall in 1ary TB then, there is no specific hypersensitivity to the bacilli, and you only get a relatively mild inflammatory rxn with a bit of caseous necrosis. But in 2dary TB the sensitised T cells recognize the organism and recruit macrophages which form large granulomas and caseous necrosis is extensive the tubercle bacilli are very hard to eradicate even when host resistance is strong

Lung tumours These are either pimary or secondary. Primary - Fig 14.25 pg 349 90% of these are carcinomas. Lung cancer is the leading cause of death from cancer in the world, and has a poor overall prognosis, about 5% 5-year survival Causes: SMOKING. Occupational hazards (E.g. asbestos, inhaled dusts, others), environmental exposures (E.g. radon from rock), pulmonary fibrosis (i.e. some peripheral lung cancers occur in areas of fibrous scarring, from infarcts or TB for example). Clinical features: weight loss, cough, haemoptysis, dyspnoea and chest pain (usually pleuritic) are common. HPO, clubbing Metastases:common sites are lymph, bone, brain, liver and adrenals. Paraneoplastic effects are common (bc of ectopic hormones):: ACTH and ADH from small cell lung carcinomas PTH from squamous cell carcinomas Can be centrally in the lung (causing lung obstruction - and then maybe collapse or consolidation of lobe or whole lung. Can also infiltrate medially into the mediastinum and thereby present bc of this, e.g. with hoarseness) or in the periphery (can cause pleural effusion if the pleura are involved, or the tumour can extend into the chest wall and cause pain). Large tumours can cavitate. Morphology: ulceration is common, so sputum may be blood stained and contain malignant cells, which you can detect cytologically, or by bronchoscopial biopsy Histologically classification: squamous cell carcinoma (SqCC) 20-30% incidence most closely associated with cigarette smoking tumours usually central, often haemmorhage and necrosis with cavitation. Mets locally to hilar lymph nodes usually, then distant later small cell lung carcinoma (SCLC) 15-20% usually in hilar bronchus, they mets very early producing bulky, widespread 2dary deposits adenocarcinoma (AC) 30-40% central or peripheral - usually single lesions large cell undifferentiated carcinoma (LCUC) 10-15% usually central, they are highly aggressive and destructive lesions with haemmorrhage and necrosis carcinoid tumours 5% low grade, malignant tumors arising mainly in central airways - high vascular, px present with haemoptysis or bronchial obstruction. These tumours have a good prognosis - however some may produce ACTH and be a rare cause of Cushings primary tumours other than carcinomas are rare, they are classifed as: benign - e.g. bronchial gland adenomas, which are polypoid or sessile lesions in a bronchus. Benign mesenchymal tumours may arise anyware that mesenchyme (connective tissue) occur, so you can find lipomas for example in the lung malignant - sarcomas, lymphomas though practically, there are divided into small cell and non small cell carcinomas. You can get mixed differentiation though.

Staging: the stage at which the px presents is very important. The TNM staging system is used (pathological classification) though the Mountain classification is also used to group px together for trials Treatment: non small cell: complete surgical resection, only achievable in tumours confined to the lung or with limited hilar node involvement. This is contraindicated in px where spread has gone to mediastinal nodes, or there is metastatic spread to other structures. Chemo and radiotherapy may be used radically or palliatively in px who have either inoperable disease or who are unfit on medical grounds for resection. small cell: usually metastasized, so surgery not helpful. Chemo and radiotherapy combo can induce remission, but only sustained in few px

Secondary more common than primary (but someone presenting for the first time with a lung tomour is more likely to have a primary) metastases are from blood or lymphatic spread - pulmonary metastases are common from sarcomas, carcinomas and lymphomas there is usually discrete nodules spread throughout both lungs, but lymph may be involved (lymphangitis carcinomatosa) Common cancers giving rise to lung secondaries are from the breast, kidney and GIT

Objective 2: Review the principles of neoplasia Objective 3: Identify the normal lung microanatomy Objective 4: List the principles of spread of tumour Mets occur when malignant tumours spread from their site of origin to a distant site, forming a secondary tumours. The total tumour burden from this can be very great, and the total mass of the secondary tumours can outweigh that of the primary tumour, e.g. a liver laden with metastases wieghs several kg more than normal. Extensive metastatic disease is called carcinomatosis. Mets can sometimes be the presenting feature however. bone pain or fractures bc of skeletal metastases palpable lymph nodes Metastatic cascade Neoplastic cells have to undergo a series of events before they become a metastatic tumour - and only some of the neoplastic cells have the necessary properties to go the full length and complete the cascade. The sequence is detailed in Fig 11.33 on page 253. When the cells reach their eventual site of metastasis, they once again go through the same events that took place when the primary tumour grew - i.e. the cells proliferate, grow a blood supply to grow big, etc. Routes: haematogenous (by blood. Mets are formed in the organs that are perfused from blood from tumour), lymphatic (i.e. mets form in regional lymph nodes) transcoleomic (pleural, pericardial and peritoneal cavities), implantation (accidental spillage of tumour cells in surgery is an example) Carcinomas: lymph spread (at least initially)

Sarcomas: haem spread Haem spread: BONE is a preferred site for haem mets from FIVE CARCINOMAS: breast, lung, kidney, thyroid and prostate (others are liver, brain). Usually multiple 2dary mets. Lymph spreads: after reaching the node through the afferent lymph channel, the tumour cells settle and start growing in the periphery, and then end up replacing it gradually (ungrateful bastards). Such mets often interrupt lymph flow, thus causing oedema in the territory it drains. Transcolomic mets: these cavities are common for mets, and result in an effusion of protein-rich, neoplastic cell rich into the cavity, which may contain fibrin. Aspiration of the fluid is very important for diagnosis. Ascites can be due to abdo tumours, but ovarian primaries are particularly prone to ascites.

Objective 5: Recognize the immunosuppressed patient and some of the associated complications Defects in immunity are PRIMARY - because of intrinsic defect of immune system - or SECONDARY, because of underlying disease. Such defects may involve specific or non-specific (innate) immune mechanisms. Immunodefiency presents as SPUR - serious, persistent, unusual and recurrent infections. PRIMARY Groups include: Primary antibody defiencies this can be defects in synthesizing ALL the immunoglobulin classes panhypogammaglobuilinaemia) or only one class or subclass -selective defiency hallmarks: recurrent infections of upper and lower respiratory tracts, skin sepsis (boils, abscesses, cellulitis), gut infection, meningitis, arthritis, splenomegaly or purpura commonest infecting organisms are pyogenic bacteria, e.g. staphylococci, H. influenzae, Strep. pneumoniae rarely diagnostic physical signs Selective IgA defiency is commonest primary defiency of specific immunity - this is undetectable serum IgA levels with normal concentrations of IgG and IgA. Most px are asymptomatic, but are predisposed to certain things: recurrent infections, autoimmune phenomena (autoantibodies or autoimmune disease (rheumatoid, SLE, coaeliac), allergy) there are more, read on page 177 Primary defects in cell mediated immunity defects in T cells are usually accompanied by defects in B cells diGeorge syndrome, SCID Primary defects in phagocyte function chronic granulomatous disease (CGD) Primary complement defiency

SECONDARY these are far more common than primary causes levels of immune components are the result of a balance between catabolism and synthesis, so low levels = decrease in production or accelerated catabolism or loss Possible causes: protein-energy malnutrition - malnourished people have impaired specific antibody production after immunisation (reverses with diet) lymphoproliferative diseases -e.g. multiple myeloma, chronic lymphocytic leukaemia, non-Hodgkins lymphoma are prone to infection

Immunosuppresive drugs - organ transplant drugs can cause opportunistic infections SPLENECTOMY - death can result from overwhelming infxn with Strep. pneumoniae, of all things! Need pneumoccocal vaccine In some infections, the micro-organism actually suppresses the immune system instead of stimulating it e.g. measles, CMV, rubella, infectious mononucleosis, viral hep, HIV AIDS AIDS is caused by the retroviruses (=RNA virus) HIV types 1 and 2. About of new HIV infections occur in women, and vertical transmission (mother-child) through breastfeeding or before or after childbirth is common. Transmission: heterosexual or homosexual intercourse sharing contaminated needles and syringes by IV drug abusers, or in those parts of the world where contaminated equipment is used receiving infected blood/blood products, donated organs or semen Clinical spectrum: HIV actually produces a spectrum of disorders. Note that seroconversion = the production of antibodies to HIV. CDC I: Transient, acute glandular fever like illness may occur in 10-20% of people within a few weeks of initial infection. Precedes seroconversion. CDC II: An asymptomatic period, lasting for 2-10 years or more, in seropositive px CDC III: Asymptomatic persistent generalized lympadenopathy (PGL) enlarged nodes in 2+ extra-inguinal sites, that persist for at least 3 months w/o any other illness that can cause lymphadenopathy CDC IV A: AIDS related complex- clinical features shown by some seropositives: unexplained lymphadenopathy, diarrhoea, night sweats, oral candidiasis, weight loss CDC IV B: Chronic meningitis, cerebral lymphoma, encephalopathy, dementia Rmb HIV is neurotropic (=tends to attack the NS preferentially). These may occur after initial acute aseptic meningitis, encephalopathy, myelopathy and neuropathy around time of seroconversion. CDC IV C & D: Opportunistic infections and tumours - dominant clinical presentations of AIDS. typical infections: Pneumocystis jiroveci pneumonia, CMV, herpes simplex typical tumours: Kaposis sarcoma, non-Hodgkins lymphoma Hallmarks of HIV progression: the HIV virus replicates extremely fast, so the immune system has a massive task to control it - so the hallmark of progression is a fall in the absolute number of CD4+ T cells. Even when HIV is latent clinically, the destruction of CD+ cells still goes on in lymph nodes and other lymphoid organs until it cant be contained and reappears in the blood. Objective 6: Discuss the pathology of COPD Obstructive airways disease is divided into two categories: localized and diffuse. Localized This is caused by mechanical factors, e.g. foreign body or tumour obstructing the airway. The area involved is limited. The obstruction causes lipid laden macrophages to fill the alveolar spaces distal to the obstruction, which may lead to bronchopneumonia and perhaps bronchiectasis. Clinical symptoms: expiratory wheeze over affected lobe, stridor (if partial obstruction of trachea or larynx) Diffuse