PNEUMONIAS  

Pneumonia is defined as acute inflammation of the lung parenchyma distal to the terminal bronchioles which consist of the respiratory bronchiole, alveolar ducts, alveolar sacs and alveoli. The terms 'pneumonia' and 'pneumonitis' are often used synonymously for inflammation of the lungs, while 'consolidation' (meaning solidification) is the term used for macroscopic and radiologic appearance of the lungs in pneumonia.

 PATHOGENESIS. 
 The microorganisms gain entry into the lungs by one of the following four routes: 
 1. Inhalation of the microbes. 
 2. Aspiration of organisms. 
 3. Haematogenous spread from a distant focus. 
 4.  Direct spread from an adjoining site of infection.

Failure of defense mechanisms and presence of certain predisposing factors result in pneumonias. 
 
 These conditions are as under: 
 1. Altered consciousness. 
 2. Depressed cough and glottic reflexes. 
 3. Impaired mucociliary transport. 
 4. Impaired alveolar macrophage function. 
 5. Endobronchial obstruction. 
 6. Leucocyte dysfunctions. 
 
 
 CLASSIFICATION. On the basis of the anatomic part of the lung parenchyma involved, pneumonias are traditionally classified into 3 main types: 
 
 1. Lobar pneumonia. 
 2. Bronchopneumonia (or Lobular pneumonia). 
 3. Interstitial pneumonia. 
 
BACTERIAL PNEUMONIA  

Bacterial infection of the lung parenchyma is the most common cause of pneumonia or consolidation of one or both the lungs. Two types of acute bacterial pneumonias are distinguished—lobar pneumonia and broncho-lobular pneumonia, each with distinct etiologic agent and morphologic changes. 
 
  1.    Lobar Pneumonia  
 Lobar pneumonia is an acute bacterial infection of a part of a lobe, the entire lobe, or even two lobes of one or both the lungs. 
 
 ETIOLOGY. 
 Following types are described: 
 1.  Pneumococcal pneumonia. More than 90% of all lobar pneumonias are caused by Streptococcus pneumoniae, a lancet-shaped diplococcus. Out of various types, type 3-S. pneumoniae causes particularly virulent form of lobar pneumonia. 
 
 2. Staphylococcal pneumonia. Staphylococcus aureus causes pneumonia by haematogenous spread of infection. 
 
 3.  Streptococcal pneumonia, β-haemolytic streptococci may rarely cause pneumonia such as in children after measles or influenza. 
 
 4.  Pneumonia by gram-negative aerobic bacteria. Less common causes of lobar pneumonia are gram-negative bacteria like Haemophilus influenzae, Klebsiella pneumoniae (Friedlander's bacillus), Pseudomonas, Proteus and Escherichia coli. 
 
 MORPHOLOGY. Laennec's original description divides lobar pneumonia into 4 sequential pathologic phases: 
 
 1.   STAGE OF CONGESTION: INITIAL PHASE 
 The initial phase represents the early acute inflammatory response to bacterial infection and lasts for 1 to 2 days. 
 
The affected lobe is enlarged, heavy, dark red and congested. Cut surface exudes blood-stained frothy fluid. 
 
Microscopic Examination 
 i) Dilatation and congestion of the capillaries in the alveolar walls. 
 ii)   Pale eosinophilic oedema fluid in the air spaces.
 iii)  A few red cells and neutrophils in the intra-alveolar fluid. 
 iv) Numerous bacteria demonstrated in the alveolar fluid by Gram's staining. 
 
  2.   RED HEPATISATION: EARLY CONSOLIDATION  
 This phase lasts for2 to 4 days. The term hepatisation in pneumonia refers to liver-like consistency of the affected lobe on cut section. 
 
 The affected lobe is red, firm and consolidated. The cut surface of the involved lobe is airless, red-pink, dry, granular and has liver-like consistency. 
 
Microscopic Examination   
 i) The oedema fluid of the preceding stage is replaced by strands of fibrin. 
 ii)   There is marked cellular exudate of neutrophils and extravasation of red cells. 
 iii)  Many neutrophils show ingested bacteria. 
 iv) The alveolar septa are less prominent than in the first stage due to cellular exudation. 
 
 3.   GREY HEPATISATION: LATE CONSOLIDATION This phase lasts for4 to 8 days. 
The affected lobe Is firm and heavy. The cut surface is dry, granular and grey in appearance with liver-like consistency. The change in colour from red to grey begins at the hilum and spreads towards the periphery. Fibrinous pleurisy is prominent. 
 
Microscopic Examination   
 i) The fibrin strands are dense and more numerous. 
 ii)   The cellular exudate of neutrophils is reduced due to disintegration of many inflammatory cells. The red cells are also fewer. The macrophages begin to appear in the exudate. 
 iii) The cellular exudate is often separated from the septal walls by a thin clear space. 
 iv) The organisms are less numerous and appear as degenerated forms. 
 
  COMPLICATIONS. Since the advent of antibiotics, serious complications of lobar pneumonia are uncommon. However, they may develop in neglected cases and in patients with impaired immunologic defenses.

 These are as under: 
 1.  Organisation. In about 3% of cases, resolution of the exudate does not occur but instead it is organised. There is ingrowth of fibroblasts from the alveolar septa resulting in fibrosed, tough, airless leathery lung tissue. 
 2.  Pleural effusion. About 5% of treated cases of lobar pneumonia develop inflammation of the pleura with effusion. 
 3.   Empyema. Less than 1% of treated cases of lobar pneumonia develop encysted pus in the pleural cavity termed empyema. 
 4.   Lung abscess. A rare complication of lobar pneumonia is formation of lung abscess. 
 5.   Metastatic infection. Occasionally, infection in the lungs and pleural cavity in lobar pneumonia may extend into the pericardium and the heart causing purulent pericarditis, bacterial endocarditis and myocarditis. 
 
 
 CLINICAL FEATURES. The major symptoms are: shaking chills, fever, malaise with pleuritic chest pain, dyspnoea and cough with expectoration which may be mucoid, purulent or even bloody. The common physical findings are fever, tachycardia, and tachypnoea, and sometimes cyanosis if the patient is severely hypoxaemic. There is generally a marked neutrophilic leucocytosis. Blood cultures are positive in about 30% of cases. Chest radiograph may reveal consolidation. 
 
 II.   Bronchopneumonia (Lobular Pneumonia)  
  Bronchopneumonia or lobular pneumonia is infection of the terminal bronchioles that extends into the surrounding alveoli resulting in patchy consolidation of the lung. The condition is particularly frequent at extremes of life (i.e. in infancy and old age), as a terminal event in chronic debilitating diseases and as a secondary infection following viral respiratory infections such as influenza, measles etc, 
 
  ETIOLOGY.

The common organisms responsible for bronchopneumonia are staphylococci, streptococci, pneumococci, Klebsiella pneumoniae, Haemophilus influenzae, and gram-negative bacilli like Pseudomonas and coliform bacteria. 
 
 Bronchopneumonia is identified by patchy areas of red or grey consolidation affecting one or more lobes, frequently found bilaterally and more often involving the lower zones of the lungs due to gravitation of the secretions. On cut surface, these patchy consolidated lesions are dry, granular, firm, red or grey in colour, 3 to 4 cm in diameter, slightly elevated over the surface and are often centred around a bronchiole. These patchy areas are best picked up by passing the fingertips on the cut surface. 
 
Microscopic Examination 

i) Acute bronchiolitis, ii) Suppurative exudate, consisting chiefly of neutrophils, in the peribronchiolar alveoli, iii) Thickening of the alveolar septa by congested capillaries and leucocytic infiltration, iv) Less involved alveoli contain oedema fluid. 
 
 COMPLICATIONS. 
 
 The complications of lobar pneumonia may occur in bronchopneumonia as well. However, complete resolution of bronchopneumonia is uncommon. There is generally some degree of destruction of the bronchioles resulting in foci of bronchiolar fibrosis that may eventually cause bronchiectasis.
 
 CLINICAL FEATURES. The patients of bronchopneumonia are generally infants or elderly individuals. There may be history of preceding bed-ridden illness, chronic debility, aspiration of gastric contents or upper respiratory infection. 
 
  VIRAL AND MYCOPLASMAL PNEUMONIA (PRIMARY ATYPICAL PNEUMONIA)  
 
 Viral and mycoplasmal pneumonia is characterised by patchy inflammatory changes, largely confined to interstitial tissue of the lungs, without any alveolar exudate. Other terms used for these respiratory tract infections are interstitial pneumonitis, reflecting the interstitial location of the inflammation, andprimary atypical pneumonia, atypicality being the absence of alveolar exudate commonly present in other pneumonias. Interstitial pneumonitis may occur in all ages. 
 
ETIOLOGY. Interstitial pneumonitis is caused by a wide variety of agents, the most common being respiratory syncytial virus (RSV). Others are Mycoplasma pneumoniae and  many viruses such as influenza and parainfluenza viruses, adenoviruses, rhinoviruses, coxsackieviruses and cytomegaloviruses (CMV). 
 
 Depending upon the severity of infection, the involvement may be patchy to massive and widespread consolidation of one or both the lungs. The lungs are heavy, congested and subcrepitant. Sectioned surface of the lung exudes small amount of frothy or bloody fluid. 
  
Microscopic Examination 

 I) Interstitial Inflammation: There is thickening of alveolar walls due to congestion, oedema and mononuclear inflammatory infiltrate comprised by lymphocytes, macrophages and some plasma cells. illness, chronic debility, aspiration of gastric contents or upper respiratory infection.
 ii)  Necrotising bronchiolitis: This is characterised by foci of necrosis of the bronchiolar epithelium, inspissated secretions in the lumina and mononuclear infiltrate in the walls and lumina. 
 
 iii) Reactive changes: The lining epithelial cells of the bronchioles and alveoli proliferate in the presence of virus and may form multinucleate giant cells and syncytia in the bronchiolar and alveolar walls. 
 
 iv) Alveolar changes: In severe cases, the alveolar lumina may contain oedema fluid, fibrin, scanty inflammatory exudate and coating of alveolar walls by pink, hyaline membrane similar to the one seen in respiratory distress syndrome. 
 
 COMPLICATIONS. 
 
 The major complication of interstitial pneumonitis is superimposed bacterial infection and its complications. Most cases of interstitial pneumonitis recover completely.
 
 CLINICAL FEATURES. 
 
 Majority of cases of interstitial pneumonitis initially have upper respiratory symptoms with fever, headache and muscle-aches. A few days later appears dry, hacking, non-productive cough with retrosternal burning due to tracheitis and bronchitis. Chest radiograph may show patchy or diffuse consolidation.  
 
  C. OTHERTYPES OF PNEUMONIAS  
 
 I.     Pneumocystis carinii Pneumonia  
 
 Pneumocystis carinii, a protozoon widespread in the environment, causes pneumonia by inhalation of the organisms as an opportunistic infection in neonates and immunosuppressed people. Almost 100% cases of AIDS develop opportunistic infection, most commonly Pneumocystis carinii pneumonia. 
 
 II.     Legionella Pneumonia 

 Legionella pneumonia or legionnaire's disease is an epidemic illness caused by gramnegative bacilli, Legionella pneumophila that thrives in aquatic environment. It was first recognised following investigation into high mortality among those attending American Legion Convention in Philadelphia in July 1976. The epidemic occurs in summer months by spread of organisms through contaminated drinking water or in air-conditioning cooling towers. Impaired host defenses in the form of immunodeficiency, corticosteroid therapy, old age and cigarette smoking play important roles. 
 
 III. Aspiration (Inhalation) Pneumonia  
 
 Aspiration or inhalation pneumonia results from inhaling different agents into the lungs. These substances include food, gastric contents, foreign body and infected material from oral cavity. A number of factors predispose to inhalation pneumonia which include: unconsciousness, drunkenness, neurological disorders affecting swallowing, drowning, necrotic oropharyngeal tumours, in premature infants and congenital tracheo-oesophageal fistula. 
 
 1.   Aspiration of small amount of sterile foreign matter such as acidic gastric contents produce chemical pneumonitis. It is characterised by haemorrhagic pulmonary oedema with presence of particles in the bronchioles. 
 
 2.    Non-sterile aspirate causes widespread bronchopneumonia with multiple areas of necrosis and suppuration. 
 
IV. Hypostatic Pneumonia 

 Hypostatic pneumonia is the term used for collection of oedema fluid and secretions in the dependent parts of the lungs in severely debilitated, bedridden patients. The accumulated fluid in the basal zone and posterior part of lungs gets infected by bacteria from the upper respiratory tract and sets in bacterial pneumonia.

 V. Lipid Pneumonia  Another variety of noninfective pneumonia is lipid pneumonia. It is of 2 types: 
 
 1.   Exogenous lipid pneumonia. This is caused by aspiration of a variety of oily materials. These are: inhalation of oily nasal drops, regurgitation of oily medicines from stomach (e.g. liquid paraffin), administration of oily vitamin preparation to reluctant children or to debilitated old patients. 
 
 2.   Endogenous lipid pneumonia. Endogenous origin of lipids causing pneumonic consolidation is more common. The sources of origin are tissue breakdown following obstruction to airways e.g. obstruction by bronchogenic cancer, tuberculosis and bronchiectasis. 

Hematological examination

This is a method by which abnormalities of the cells of the blood and their precursors in the bone marrow are investigated to diagnose the different kinds of anemia & leukemia.

Emphysema

Emphysema is a chronic lung disease. It is often caused by exposure to toxic chemicals or long-term exposure to tobacco smoke.

Signs and symptoms

loss of elasticity of the lung tissue

destruction of structures supporting the alveoli

destruction of capillaries feeding the alveoli

The result is that the small airways collapse during expiration, leading to an obstructive form of lung disease

Features are: shortness of breath on exertion

 hyperventilation and an expanded chest.

As emphysema progresses, clubbing of the fingers may be observed, a feature of longstanding hypoxia.

Emphysema patients are sometimes referred to as "pink puffers". This is because emphysema sufferers may hyperventilate to maintain adequate blood oxygen levels. Hyperventilation explains why emphysema patients do not appear cyanotic as chronic bronchitis (another COPD disorder) sufferers often do; hence they are "pink" puffers (adequate oxygen levels in the blood) and not "blue" bloaters (cyanosis; inadequate oxygen in the blood).

Diagnosis

spirometry (lung function testing), including diffusion testing

X-rays,  high resolution spiral chest CT-scan,

Bronchoscopy, blood tests, pulse oximetry and arterial blood gas sampling.

Pathophysiology :

Permanent destructive enlargement of the airspaces distal to the terminal bronchioles without obvious fibrosis

Oxygen is inhaled in normal breathing

When toxins such as smoke are breathed into the lungs, the particles are trapped by the hairs and cannot be exhaled, leading to a localised inflammatory response. Chemicals released during the inflammatory response (trypsin, elastase, etc.) are released and begin breaking down the walls of alveoli. This leads to fewer but larger alveoli, with a decreased surface area and a decreased ability to take up oxygen and loose carbon dioxide. The activity of another molecule called alpha 1-antitrypsin normally neutralizes the destructive action of one of these damaging molecules.

After a prolonged period, hyperventilation becomes inadequate to maintain high enough oxygen levels in the blood, and the body compensates by vasoconstricting appropriate vessels. This leads to pulmonary hypertension. This leads to enlargement and increased strain on the right side of the heart, which in turn leads to peripheral edema (swelling of the peripherals) as blood gets backed up in the systemic circulation, causing fluid to leave the circulatory system and accumulate in the tissues.

Emphysema occurs in a higher proportion in patient with decreased alpha 1-antitrypsin (A1AT) levels

Prognosis and treatment

Emphysema is an irreversible degenerative condition

Supportive  treatmentis by supporting the breathing with anticholinergics, bronchodilators and (inhaled or oral) steroid medication, and supplemental oxygen as required

Lung volume reduction surgery (LVRS) can improve the quality of life for only  selected patients.

Haemolytic anaemia 

Anemia due to increased red cell destruction (shortened life span)

Causes:

A. Corpuscular defects:

1.Membrane defects:

    - Spherocytosis.
    - Elliptocytosis.

2. Haemoglobinopathies:

    - Sickle cell anaemia.
    - Thalassaemia
    - Hb-C, HBD, HbE.
    
3. Enzyme defects .deficiency of:

    - GIucose -6 phosphate dehydrogenase (G6-PD)
    - Pyruvate kinase
    
4. Paroxysmal nocturnal haemoglobinuria.

B. Extracorpusular mechanisms 

1. Immune based:
    - Autoimmune haemolytic anaemia.
    - Haemolytic disease of new born.
    - Incompatible transfusion.
    - Drug induced haemolysis
    
2. Mechanical haemolytic anaemia.
3. Miscellaneous due to :

    - Drugs and chemicals.
    - Infections.
    - Burns.

features of haemolytic anaemia

- Evidence of increased Hb breakdown:

    -> Unconjugated hyperbilirubinaemia.
    -> Decreased plasma haptoglobin.
    -> Increased urobilinogen and stercobilinogen.
    -> Haemoglobinaemia, haemoglobinuria and haemosiderinuria if Intravascular haemolysis occurs.

- Evidence or compensatory erythroid hyperplasia:

    -> Reticulocytosis and nucleated RBC in peripheral smear.
    -> Polychromasia and macrocytes 
    -> Marrow erythroid hyperplasia
    -> Skull and other bone changes.

- Evidences of damage to RBC:

    -> Spherocytes and increased osmotic fragility
    -> Shortened life span.
    -> Fragmented RBC.
    -> Heinz bodies.
 

Osteogenesis Imperfecta (OI) (Brittle bone diseases) 

It is a group of hereditary disorders caused by gene mutations that eventuate in defective synthesis of and thus premature degradation of type I collagen. The fundamental abnormality in all forms of OI is too little bone, resulting in extreme susceptibility to fractures. The bones show marked cortical thinning and attenuation of trabeculae. 

Extraskeletal manifestations also occur because type I collagen is a major component of extracellular matrix in other parts of the body. The classic finding of blue sclerae  is attributable to decreased scleral collagen content; this causes a relative transparency that allows the underlying choroid to be seen. Hearing loss can be related to conduction defects in the middle and inner ear bones, and small misshapen teeth are a result of dentin deficiency 

SMALL INTESTINE 

Congenital anomalies 

1. Meckel's diverticulum (a true diverticulum) is due to persistence of the omphalomesenteric vitelline duct. 
2. Atresia is a congenital absence of a region of bowel, leaving a blind pouch or solid fibrous cord. 
3. Stenosis refers to a narrowing of any region of the gastrointestinal tract, which may cause obstruction. 
4. Duodenal diverticula are areas of congenital weakness permitting saccular enlargement. The duodenum is the most common region of the small bowel to contain diverticula. 
5. Diverticula of jejunum and ileum are herniations of mucosa and submucosa at points where the mesenteric vessels and nerves enter. 

Infections

1. Bacterial enterocolitis may be caused by the ingestion of preformed bacterial toxins, producing symptoms ranging from severe but transient nausea, vomiting, and diarrhea (Staphylococcus aureus toxin) to lethal paralysis (Clostridium botulinum toxin). Ingestion of toxigenic bacteria with colonization of the gut (e.g., Vibrio cholera, toxigenic E. coli, various species of Campylobacter jejuni, Shigella, salmonel
Yersinia, and many others) is another potential cause. 

2. Nonbacterial gastroenterocolitis
a. Viral 
(1) Rotavirus (children)
(2) Parvovirus (adults) 
b. Fungal-Candida 
c. Parasitic 
(1 ) Entamoeba histolytica 
(2) Giardia lamblia 

3. In HIV patients. Causes of infectious diarrhea in HIV patients include Cryptosporidium, Microsporidia, isospora belli, CMV, and M. avium-intracellulare. 

C. Malabsorption is defined as impaired intestinal absorption of dietary constituents. 
Clinical features include diarrhea,steatorrhea, weakness, lassitude, and weight loss. Steatorrhea results in deficiency of fat-soluble vitamins (A, D, E, K) and calcium. 

1. Celiac sprue
a. Etiology. Celiac sprue (nontropical sprue or gluten enteropathy) is caused by an allergic, immunologic, or toxic reaction to the gliadin component of gluten. There is a genetic predisposition. 

Symptoms:
– Steatorrhea, abdominal distention, flatulence, fatigue, and weight loss

Complications:
– Iron and vitamin deficiency
– Risk of lymphoma (T-cell type)

Extraintestinal manifestation:
– Dermatitis herpetiformis (a pruritic papulovesicular rash with IgA deposits at the dermoepidermal junction) 

2. Tropical sprue

Etiology. Tropical sprue is of unknown etiology, but may be  caused by enterotoxigenic E. coli. 

3. Disaccharidase deficiency is due to a deficiency of brush border enzymes. Lactase deficiency is most common. 

4. Diverticulosis Coli

- Acquired colonic diverticula are present in nearly half of the population over the age of 50
- Diverticula are associated with low-fiber, low-residue diets
- Etiology is most likely high intraluminal pressure required for propulsion of hard, small stools
- Complications include hemorrhage, acute diverticulitis, perforation, fistula formation 

Obstructive lesions

Hernias cause 15% of small intestinal obstruction. They are due to a protrusion of a serosa-lined sac through a weakness in the wall of the peritoneal cavity. They occur most commonly at the inguinal and femoral canals, at the umbilicus, and with scars. They may lead to entrapment, incarceration, and strangulation of the bowel. 

Tumors of the small bowel account for only 5% of gastrointestinal tumors. 

Benign tumors in descending order of frequency include:
leiomyomas, lipomas, adenomas (polyps), angiomas, and fibromas. Adenomatous polyps are most common in the stomach and duodenum and may be single or multiple, sessile or pedunculated. The larger the polyp, the greater the incidence of malignant transformation. 

Malignant tumors, in descending order of frequency, include: endocrine cell tumors, lymphomas, adenocarcinomas, and leiomyosarcomas. 

Idiopathic Inflammatory Bowel Disease (IBD)

- Chronic, relapsing, idiopathic inflamamtory disease of the GI tract
Crohn’s Disease
– Transmural granulomatous disease affecting any portion of the GI tract
Ulcerative Colitis
– Superficial, non-granulomatous inflammatory disease restricted to the colon

Ulcerative Colitis
- Bloody mucoid diarrhea, rarely toxic megacolon
- Can begin at any age, peaks at 20-25 years
- Annual incidence of ~10 per 100,000 in US
- Negligible risk of cancer in the first 10 years, but 1% per year risk of cancer thereafter
- Good response to total colectomy if medical therapy fails

Macroscopic
- Normal serosa
- Bowel normal thickness
- Continuous disease
- Confluent mucosal ulceration
- Pseudopolyp formation

Microscopic
- Crypt distortion + shortening
- Paneth cell metaplasia
- Diffuse mucosal inflammation
- Crypt abscesses
- Mucin depletion
- Mucosal ulceration

Crohn’s Disease

- Variable and elusive clinical presentation with diarrhea, pain, weight loss, anorexia, fever
- Can begin at any age, peaks at 15-25 years
- Annual incidence of ~3 per 100,000 in US
- Many GI complications and extracolonic manifestations
- Risk of cancer less than in UC
- Poor response to surgery 

Macroscopic
Fat wrapping
Thickened bowel wall
Skip Lesions
Stricture formation
Cobblestoned mucosa
Ulceration

Microscopic
- Cryptitis and crypt abscesses
- Transmural inflammation
- Lymphoid aggregates +/- granulomas
- “Crohn’s rosary”
- Fissuring
- Neuromuscular hyperplasia