Pathoma_Husain

Pathoma_Husain. B. Causes include amyloidosis, sarcoidosis, endocardial fibroelastosis (children, Fig. 8.21), and Loeffler syndrome (endomyocardial fibrosis with an eosinophilic infiltrate and eosinophilia). C. Presents as congestive heart failure; classic finding is low-voltage EKG with diminished QRS amplitude. Fig. 8.19 Myocarditis. Fig. 8.20 Myofiber disarray, hypertrophic Fig. 8.21 Endocardial fibroelastosis. (Courtesy of cardiomyopathy. humpath.com) I. MYXOMA A. Benign mesenchymal tumor with a gelatinous appearance and abundant ground substance on histology 1. Most common primary cardiac tumor in adults B. Usually forms a pedunculated mass in the left atrium that causes syncope due to obstruction of the mitral valve II. RHABDOMYOMA A. Benign hamartoma of cardiac muscle 1. Most common primary cardiac tumor in children; associated with tuberous sclerosis B. Usually arises in the ventricle III. METASTASIS A. Metastatic tumors are more common in the heart than primary tumors.


Pathoma_Husain

Pathoma_Husain. B. Usually arises in the ventricle III. METASTASIS A. Metastatic tumors are more common in the heart than primary tumors. 1. Common metastases to the heart include breast and lung carcinoma, melanoma, and lymphoma. B. Most commonly involve the pericardium, resulting in a pericardia! effusion I. RHINITIS A. Inflammation of the nasal mucosa; rhinovirus is the most common cause. B. Presents with sneezing, congestion, and runny nose (common cold) C. Allergic rhinitis is a subtype of rhinitis due to a type I hypersensitivity reaction (e.g., to pollen) 1. Characterized by an inflammatory infiltrate with eosinophils 2. Associated with asthma and eczema II. NASAL POLYP A. Protrusion of edematous, inflamed nasal mucosa B. Usually secondary to repeated bouts of rhinitis; also occurs in cystic fibrosis and aspirin-intolerant asthma 1. Aspirin-intolerant asthma is characterized by the triad of asthma, aspirininduced bronchospasms, and nasal polyps; seen in 10% of asthmatic adults


Pathoma_Husain

Pathoma_Husain. III. ANGIOFIBROMA A. Benign tumor of nasal mucosa composed of large blood vessels and fibrous tissue; classically seen in adolescent males B. Presents with profuse epistaxis IV. NASO PHARYNGEAL CARCINOMA A. Malignant tumor of nasopharyngeal epithelium B. Associated with EBY; classically seen in African children and Chinese adults C. Biopsy usually reveals pleomorphic keratin-positive epithelial cells (poorly differentiated squamous cell carcinoma) in a background of lymphocytes. D. Often presents with involvement of cervical lymph nodes I. ACUTE EPIGLOTTITIS A. Inflammation of the epiglottis (Fig. 9.1); H influenzae type b is the most common cause, especially in nonimmunized children. B. Presents with high fever, sore throat, drooling with dysphagia, muffled voice, and inspiratory stridor; risk ofairway obstruction II. LARYNGOTRACHEOBRONCHITIS (CROUP) A. Inflammation of the upper airway; parainfluenza virus is the most common cause.


Pathoma_Husain

Pathoma_Husain. II. LARYNGOTRACHEOBRONCHITIS (CROUP) A. Inflammation of the upper airway; parainfluenza virus is the most common cause. B. Presents with a hoarse, "barking" cough and inspiratory stridor III. VOCAL CORD NODULE (SINGER'S NODULE) A. Nodule that arises on the true vocal cord B. Due to excessive use of vocal cords; usually bilateral (Fig. 9.2A) 1. Composed of degenerative (myxoid) connective tissue (Fig. 9.2B) pathoma.com C. Presents with hoarseness; resolves with resting ofvoice IV. A. Benign papillary tumor of the vocal cord B. Due to HPV 6 and 11; papillomas are usually single in adults and multiple in children. C. Presents with hoarseness V. A. Squamous cell carcinoma usually arising from the epithelial lining of the vocal cord B. Risk factors are alcohol and tobacco; can rarely arise from a laryngeal papilloma C. Presents with hoarseness; other signs include cough and stridor. I. PNEUMONIA A. Infection of the lung parenchyma


Pathoma_Husain

Pathoma_Husain. C. Presents with hoarseness; other signs include cough and stridor. I. PNEUMONIA A. Infection of the lung parenchyma B. Occurs when normal defenses are impaired (e.g., impaired cough reflex, damage to mucociliary escalator, or mucus plugging) or organism is highly virulent. C. Clinical features include fever and chills, productive cough with yellow-green (pus) or rusty (bloody) sputum, tachypnea with pleuritic chest pain, decreased breath sounds, crackles, dullness to percussion, and elevated WBC count. D. Diagnosis is made by chest x-ray, sputum gram stain and culture, and blood cultures. E. Three patterns are classically seen on chest x-ray: lobar pneumonia, bronchopneumonia, and interstitial pneumonia. Fig. 9.1 Acute epiglottitis. (Courtesy of Stephanie Fig. 9.2 Vocal cord nodules. A, Gross appearance. B, Microscopic appearance. (B, Reproduced from Rozell, MD) wikipedia.org, CCBY-SA 3.0) .( • ~;"I. ❖ ~:;: , • "' . • •~~ '• . •. r,;. ·:£;1« ·"fl:


Pathoma_Husain

Pathoma_Husain. ·:£;1« ·"fl: Fig. 9.3 Lobar pneumonia. A, X-ray appearance. B, Red hepatization. C, Acute inflammation involving alveolar sacs. (A, Courtesy of James Heilman, MD, Wikipedia. B, Courtesy of Yale Rosen, MD) II. LOBAR PNEUMONIA A. Characterized by consolidation of an entire lobe of the lung (Fig. 9.3A) B. Usually bacterial; most common causes are Streptococcus pneumoniae (95%) and Klebsiella pneumoniae (Table 9.1) C. Classic gross phases oflobar pneumonia 1. Congestion-due to congested vessels and edema 2. Red hepatization-due to exudate, neutrophils, and hemorrhage filling the alveolar air spaces, giving the normally spongy lung a solid consistency (Fig. 9.3B,C) 3. Gray hepatization-due to degradation of red cells within the exudate 4. Ill. BRONCHOPNEUMONIA A. Characterized by scattered patchy consolidation centered around bronchioles; often multifocal and bilateral (Fig. 9.4) B. Caused by a variety of bacterial organisms (Table 9.2) IV.


Pathoma_Husain

Pathoma_Husain. A. Characterized by scattered patchy consolidation centered around bronchioles; often multifocal and bilateral (Fig. 9.4) B. Caused by a variety of bacterial organisms (Table 9.2) IV. A. Characterized by diffuse interstitial infiltrates (Fig. 9.5) B. Presents with relatively mild upper respiratory symptoms (minimal sputum and low fever); 'atypical' presentation C. Caused by bacteria or viruses (Table 9.3) V. A. Seen in patients at risk for aspiration (e.g., alcoholics and comatose patients) B. Most often due to anaerobic bacteria in the oropharynx (e.g., Bacteroides, Fusobacterium, and Peptococcus) Fig. 9.4 Bronchopneumonia. A, X-ray appearance. B, Gross appearance. (B, Courtesy of Yale Rosen, MD) Fig. 9.5 Interstitial pneumonia. A, X-ray appearance. B, Inflammatory infiltrate involving interstitium. Table 9.2: Causes of Bronchopneumonia 2nd most common cause of secondary pneumonia; often complicated by abscess or empyema


Pathoma_Husain

Pathoma_Husain. Table 9.2: Causes of Bronchopneumonia 2nd most common cause of secondary pneumonia; often complicated by abscess or empyema Common cause of secondary pneumonia and pneumonia superimposed on COPD (leads to exacerbation of COPD) Community-acquired pneumonia and pneumonia superimposed on COPD (leads to exacerbation of COPD) Community-acquired pneumonia, pneumonia superimposed on COPD, or pneumonia in immunocompromised states; transmitted from water source Intracellular organism that is best visualized by silver stain Table 9.3: Causes of Interstitial (Atypical) Pneumonia Most common cause of atypical pneumonia, usually affects young adults (classically, military recruits or college students living in a dormitory). Complications include autoimmune hemolytic anemia (IgM against I antigen on RBCs causes cold hemolytic anemia) and erythema multiforme. Not visible on gram stain due to lack ofcell wall Second most common cause of atypical pneumonia in young adults


Pathoma_Husain

Pathoma_Husain. Second most common cause of atypical pneumonia in young adults Most common cause of atypical pneumonia in infants Atypical pneumonia with posttransplant immunosuppression or chemotherapy Atypical pneumonia in the elderly, immunocompromised, and those with preexisting lung disease. Also increases the risk for superimposed S aureus or H influenzae bacterial pneumonia Atypical pneumonia with high fever (Q fever); seen in farmers and veterinarians (Coxiella spores are deposited on cattle by ticks or are present in cattle placentas). Coxiella is a rickettsial organism, but it is distinct from most rickettsiae because it (1) causes pneumonia, (2) does not require arthropod vector for transmission (survives as highly heat-resistant endospores), and (3) does not produce a skin rash. C. Classically results in a right lower lobe abscess 1. Anatomically, the right main stem bronchus branches at a less acute angle than the left. VI. TUBERCULOSIS (TB)


Pathoma_Husain

Pathoma_Husain. C. Classically results in a right lower lobe abscess 1. Anatomically, the right main stem bronchus branches at a less acute angle than the left. VI. TUBERCULOSIS (TB) A. Due to inhalation of aerosolized Mycobacterium tuberculosis B. Primary TB arises with initial exposure. 1. Results in focal, caseating necrosis in the lower lobe of the lung and hilar lymph nodes that undergoes fibrosis and calcification, forming a Ghon complex (Fig. 9.6A) 2. Primary TB is generally asymptomatic, but leads to a positive PPD. C. Secondary TB arises with reactivation ofMycobacterium tuberculosis. 1. Reactivation is commonly due to AIDS; may also be seen with aging 2. 3. Forms cavitary foci of caseous necrosis; may also lead to miliary pulmonary TB or tuberculous bronchopneumonia 4. Clinical features include fevers and night sweats, cough with hemoptysis, and weight loss. 5. Biopsy reveals caseating granulomas; AFB stain reveals acid-fast bacilli (Fig. 9.6B,C). 6.


Pathoma_Husain

Pathoma_Husain. Clinical features include fevers and night sweats, cough with hemoptysis, and weight loss. 5. Biopsy reveals caseating granulomas; AFB stain reveals acid-fast bacilli (Fig. 9.6B,C). 6. Systemic spread often occurs and can involve any tissue; common sites include meninges (meningitis), cervical lymph nodes, kidneys (sterile pyuria), and lumbar vertebrae (Pott disease). I. BASIC PRINCIPLES A. Group of diseases characterized by airway obstruction; lung does not empty, and air is trapped. 1. Volume ofair that can be forcefully expired is decreased (-.I, FVC), especially during the first second ofexpiration (-.l,-.l, FEV); results in -.I, FEV :FVC ratio 2. Total lung capacity (TLC) is usually increased due to air trapping. II. CHRONIC BRONCHITIS A. Chronic productive cough lasting at least 3 months over a minimum of 2 years; highly associated with smoking B. Characterized by hypertrophy of bronchial mucous glands (Fig. 9.7)


Pathoma_Husain

Pathoma_Husain. A. Chronic productive cough lasting at least 3 months over a minimum of 2 years; highly associated with smoking B. Characterized by hypertrophy of bronchial mucous glands (Fig. 9.7) Fig. 9.6 Tuberculosis. A, Ghon focus. B, Caseating granuloma. C, AFB staining of M tuberculosis. (A, Courtesy of Ya le Rosen, MD) 1. Leads to increased thickness of mucus glands relative to bronchial wall thickness (Reid index increases to > 50%; normal is < 40%). C. Clinical features 1. Productive cough due to excessive mucus production 2. Cyanosis ('blue bloaters')-Mucus plugs trap carbon dioxide; t Paco2 and ..I.-Pao2 3. Increased risk of infection and cor pulmonale III. EMPHYSEMA A. Destruction of alveolar air sacs (Fig. 9.8) 1. Loss of elastic recoil and collapse of airways during exhalation results in obstruction and air trapping. B. Due to imbalance of proteases and anti proteases 1. Inflammation in the lung normally leads to release of proteases by neutrophils and macrophages. 2.


Pathoma_Husain

Pathoma_Husain. B. Due to imbalance of proteases and anti proteases 1. Inflammation in the lung normally leads to release of proteases by neutrophils and macrophages. 2. a -anti trypsin (Al AT) neutralizes proteases. 3. Excessive inflammation or lack of AlAT leads to destruction of the alveolar air sacs. C. Smoking is the most common cause of emphysema. 1. Pollutants in smoke lead to excessive inflammation and protease-mediated damage. 2. Results in centriacinar emphysema that is most severe in the upper lobes D. AlAT deficiency is a rare cause of emphysema. 1. Lack of antiprotease leaves the air sacs vulnerable to protease-mediated damage. 2. Results in panacinar emphysema that is most severe in the lower lobes 3. Liver cirrhosis may also be present. i. Al AT deficiency is due to misfolding of the mutated protein. ii. Mutant AlAT accumulates in the endoplasmic reticulum ofhepatocytes, resulting in liver damage.


Pathoma_Husain

Pathoma_Husain. i. Al AT deficiency is due to misfolding of the mutated protein. ii. Mutant AlAT accumulates in the endoplasmic reticulum ofhepatocytes, resulting in liver damage. 111. Biopsy reveals pink, PAS-positive globules in hepatocytes (Fig. 9.9). 4. Disease severity is based on the degree of AlAT deficiency. i. PiM is the normal allele; two copies are usually expressed (PiMM). ii. PiZ is the most common clinically relevant mutation; results in significantly low levels of circulating AlAT iii. PiMZ heterozygotes are usually asymptomatic with decreased circulating levels of AlAT; however, significant risk for emphysema with smoking exists. iv. PiZZ homozygotes are at significant risk for panacinar emphysema and cirrhosis. Fig. 9.7 Chronic bronchitis. Fig. 9.8 Emphysema. A, Gross appearance. B, Microscopic appearance. (A, Courtesy of Yale Rosen, MD) E. Clinical features of emphysema include 1. Dyspnea and cough with minimal sputum 2.


Pathoma_Husain

Pathoma_Husain. E. Clinical features of emphysema include 1. Dyspnea and cough with minimal sputum 2. Prolonged expiration with pursed lips ('pink-puffer') 3. 4. Increased anterior-posterior diameter of chest ('barrel-chest,' Fig. 9.10) 5. Hypoxemia (due to destruction of capillaries in the alveolar sac) and cor pulmonale are late complications. IV. A. Reversible airway bronchoconstriction, most often due to allergic stimuli (atopic asthma) B. Presents in childhood; often associated with allergic rhinitis, eczema, and a family history of atopy C. Pathogenesis (type I hypersensitivity) 1. Allergens induce T H2 phenotype in CD4+ T cells of genetically susceptible individuals. 2. T H2 cells secrete IL-4 (mediates class switch to IgE), IL-5 (attracts eosinophils), and IL-10 (stimulates T H2 cells and inhibits T Hl). 3. Reexposure to allergen leads to IgE-mediated activation of mast cells.


Pathoma_Husain

Pathoma_Husain. 3. Reexposure to allergen leads to IgE-mediated activation of mast cells. i. Release of preformed histamine granules and generation ofleukotrienes C4, D4, and E4 lead to bronchoconstriction, inflammation, and edema (earlyphase reaction). ii. Inflammation, especially major basic protein derived from eosinophils, damages cells and perpetuates bronchoconstriction (late-phase reaction). D. Clinical features are episodic and related to allergen exposure. 1. 2. Productive cough, classically with spiral-shaped mucus plugs (Curschmann spirals) and eosinophil-derived crystals (Charcot-Leyden crystals, Fig. 9.11). 3. Severe, unrelenting attack can result in status asthmaticus and death. E. Asthma may also arise from nonallergic causes (non-atopic asthma) such as exercise, viral infection, aspirin (e.g., aspirin intolerant asthma), and occupational exposures. V. A. Permanent dilatation of bronchi (Fig. 9.12); loss of airway tone results in air trapping.


Pathoma_Husain

Pathoma_Husain. V. A. Permanent dilatation of bronchi (Fig. 9.12); loss of airway tone results in air trapping. B. Due to severe inflammation with damage to airway walls. Causes include 1. 2. Primary ciliary dyskinesia-inherited defect of the dynein arm, which is necessary for ciliary movement. Associated with sinusitis, infertility (poor motility of sperm), and situs inversus (position of major organs is reversed, e.g., heart is on right side of thorax), which is called Kartagener syndrome Fig. 9.9 Al AT accumulation in hepatocytes. Fig. 9,10 Increased AP diameter, emphysema. Fig. 9.11 Charcot-Leyden crystals, asthma. (Courtesy of James Heilman, MD, Wikipedia) 3. 4. 5. Allergic bronchopulmonary aspergillosis-Hypersensitivity reaction to Aspergillus leads to chronic inflammatory damage; usually seen in individuals with asthma or cystic fibrosis C. Clinical features 1. Cough, dyspnea, and foul-smelling sputum 2.


Pathoma_Husain

Pathoma_Husain. C. Clinical features 1. Cough, dyspnea, and foul-smelling sputum 2. Complications include hypoxemia with cor pulmonale and secondary (AA) amyloidosis. I. BASIC PRINCIPLES A. Characterized by restricted filling of the lung; .,I.. TLC, .,I.. FEV , and .,1...,1.. FVC; FEV :FVC ratio is increased. B. Most commonly due to interstitial diseases of the lung; may also arise with chest wall abnormalities (e.g., massive obesity) II. IDIOPATHIC PULMONARY FIBROSIS A. Fibrosis oflung interstitium (Fig. 9.13) B. Etiology is unknown. Likely related to cyclical lung injury; TGF-~ from injured pneumocytes induces fibrosis. 1. Secondary causes of interstitial fibrosis such as drugs (e.g., bleomycin and amiodarone) and radiation therapy must be excluded. C. Clinical features 1. 2. Bilateral fibrosis on lung CT; initially seen in subpleural patches, but eventually results in extensive fibrosis with end-stage 'honeycomb' lung 3. 4. Definitive treatment is lung transplantation.


Pathoma_Husain

Pathoma_Husain. 4. Definitive treatment is lung transplantation. III. PNEUMOCONIOSES A. Interstitial fibrosis due to occupational exposure; requires chronic exposure to small particles that are fibrogenic (Table 9.4) 1. Alveolar macrophages engulf foreign particles and induce fibrosis. IV. SARCOIDOSIS A. Systemic disease characterized by noncaseating granulomas in multiple organs; classically seen in African American females Fig. 9.12 Bronchiectasis. (Courtesy of Yale Rosen, Fig. 9.13 Interstitial fibrosis, idiopathic MD) pulmonary fibrosis. Table 9.4: Summary of Pneumoconioses Massive exposure leads to diffuse Coal Workers' fibrosis ('black lung'); associated Pneumoconiosis with rheumatoid arthritis (Caplan syndrome) silica miners the lung Beryllium; seen in beryllium Noncaseating granulomas in the Berylliosis miners and workers in the lung, hilar lymph nodes, and aerospace industry systemic organs


Pathoma_Husain

Pathoma_Husain. Beryllium; seen in beryllium Noncaseating granulomas in the Berylliosis miners and workers in the lung, hilar lymph nodes, and aerospace industry systemic organs Fibrosis oflung and pleura (plaques) with increased risk for Asbestos fibers; seen in lung carcinoma and mesothelioma;Asbestosis construction workers, plumbers, lung carcinoma is more commonand shipyard workers than mesothelioma in exposed individuals. B. Etiology is unknown; likely due to CD4 • helper T-cell response to an unknown antigen C. Granulomas most commonly involve the hilar lymph nodes and lung (Fig. 9.15A), leading to restrictive lung disease. 1. Characteristic stellate inclusions ('asteroid bodies') are often seen within giant cells of the granulomas (Fig. 9.15B). D. Other commonly involved tissues include the uvea (uveitis), skin (cutaneous nodules or erythema nodosum), and salivary and lacrimal glands (mimics Sjogren syndrome); almost any tissue can be involved. E. Clinical features 1. 2. 3.


Pathoma_Husain

Pathoma_Husain. E. Clinical features 1. 2. 3. Hypercalcemia (I-alpha hydroxylase activity of epithelioid histiocytes converts vitamin D to its active form) 4. Treatment is immunosuppression; often resolves spontaneously without treatment. Mild exposure to carbon (e.g., pollution) results in anthracosis (collections of carbon-laden macrophages); not clinically significant Increased risk for TB; silica impairs phagolysosome formation by macrophages. Lesions may contain long, goldenbrown fibers with associated iron (asbestos bodies, Fig. 9.14), which confirm exposure to asbestos Fig. 9.14 Asbestos bodies. (Courtesy of Nephron, Fig. 9.15 Sarcoidosis. A, Noncaseating granuloma involving lung. B, Asteroid body. GNU-FOL vl.3) V. HYPERSENSITIVITY PNEUMONITIS A. Granulomatous reaction to inhaled organic antigens (e.g., pigeon breeder's lung) B. Presents with fever, cough, and dyspnea hours after exposure; resolves with removal of the exposure C. Chronic exposure leads to interstitial fibrosis.


Pathoma_Husain

Pathoma_Husain. B. Presents with fever, cough, and dyspnea hours after exposure; resolves with removal of the exposure C. Chronic exposure leads to interstitial fibrosis. I. BASIC PRINCIPLES A. High pressure in the pulmonary circuit (mean arterial pressure > 25 mm Hg; normal is 10 mm Hg) B. Characterized by atherosclerosis of the pulmonary trunk, smooth muscle hypertrophy of pulmonary arteries, and intimal fibrosis; plexiform lesions are seen with severe, long-standing disease (Fig. 9.16). C. Leads to right ventricular hypertrophy with eventual cor pulmonale D. Presents with exertional dyspnea or right-sided heart failure E. Subclassified as primary or secondary based on etiology II. PRIMARY PULMONARY HYPERTENSION A. Classically seen in young adult females B. Etiology is unknown; some familial forms are related to inactivating mutations of BMPR2, leading to proliferation ofvascular smooth muscle. III. SECONDARY PULMONARY HYPERTENSION


Pathoma_Husain

Pathoma_Husain. B. Etiology is unknown; some familial forms are related to inactivating mutations of BMPR2, leading to proliferation ofvascular smooth muscle. III. SECONDARY PULMONARY HYPERTENSION A. Due to hypoxemia (e.g., COPD and interstitial lung disease) or increased volume in the pulmonary circuit (e.g., congenital heart disease); may also arise with recurrent pulmonary embolism I. ACUTE RESPIRATORY DISTRESS SYNDROME A. Diffuse damage to the alveolar-capillary interface (diffuse alveolar damage) B. Leakage of protein-rich fluid leads to edema that combines with necrotic epithelial cells to form hyaline membranes lining alveoli (Fig. 9.17A). C. Clinical features 1. Hypoxemia and cyanosis with respiratory distress-due to thickened diffusion barrier and collapse of air sacs (increased surface tension) 2. 'White-out' on chest x-ray (Fig. 9.17B)


Pathoma_Husain

Pathoma_Husain. Hypoxemia and cyanosis with respiratory distress-due to thickened diffusion barrier and collapse of air sacs (increased surface tension) 2. 'White-out' on chest x-ray (Fig. 9.17B) D. Secondary to a variety of disease processes including sepsis, infection, shock, trauma, aspiration, pancreatitis, DIC, hypersensitivity reactions, and drugs. Fig. 9.16 Plexiform lesion, primary pulmonary Fig. 9.17 ARDS. A, Hyaline membranes. B, 'White-out' of lung on x-ray. (B, Courtesy of Samir, GNUhypertension. FDL vl.2) 1. Activation of neutrophils induces protease-and free radical-mediated damage of type I and II pneumocytes. E. Treatment 1. 2. Ventilation with positive end-expiratory pressure (PEEP) F. Recovery may be complicated by interstitial fibrosis; damage and loss of type II pneumocytes leads to scarring and fibrosis. II. NEONATAL RESPIRATORY DISTRESS SYNDROME A. Respiratory distress due to inadequate surfactant levels 1.


Pathoma_Husain

Pathoma_Husain. II. NEONATAL RESPIRATORY DISTRESS SYNDROME A. Respiratory distress due to inadequate surfactant levels 1. Surfactant is made by type II pneumocytes; phosphatidylcholine (lecithin) is the major component. 2. Surfactant decreases surface tension in the lung, preventing collapse of alveolar air sacs after expiration. 3. Lack of surfactant leads to collapse of air sacs and formation of hyaline membranes. B. Associated with 1. Prematurity-Surfactant production begins at 28 weeks; adequate levels are not reached until 34 weeks. i. Amniotic fluid lecithin to sphingomyelin ratio is used to screen for lung maturity. ii. Phosphatidylcholine (lecithin) levels increase as surfactant is produced; sphingomyelin remains constant. iii. A ratio > 2 indicates adequate surfactant production. 2. Caesarian section delivery-due to lack of stress-induced steroids; steroids increase synthesis of surfactant. 3. Maternal diabetes-Insulin decreases surfactant production. C. Clinical features 1.


Pathoma_Husain

Pathoma_Husain. Caesarian section delivery-due to lack of stress-induced steroids; steroids increase synthesis of surfactant. 3. Maternal diabetes-Insulin decreases surfactant production. C. Clinical features 1. Increasing respiratory effort after birth, tachypnea with use of accessory muscles, and grunting 2. Hypoxemia with cyanosis 3. Diffuse granularity of the lung ('ground-glass' appearance) on x-ray (Fig. 9.18) D. Complications 1. Hypoxemia increases the risk for persistence of patent ductus arteriosus and necrotizing enterocolitis. 2. Supplemental oxygen increases the risk for free radical injury. Retinal injury leads to blindness; lung damage leads to bronchopulmonary dysplasia. I. BASIC PRINCIPLES A. Most common cause of cancer mortality in the US; average age at presentation is 60 years. B. Key risk factors are cigarette smoke, radon, and asbestos. 1. Cigarette smoke contains over 60 carcinogens; 85% oflung cancer occurs in smokers.


Pathoma_Husain

Pathoma_Husain. B. Key risk factors are cigarette smoke, radon, and asbestos. 1. Cigarette smoke contains over 60 carcinogens; 85% oflung cancer occurs in smokers. i. Polycyclic aromatic hydrocarbons and arsenic are particularly mutagenic. ii. Cancer risk is directly related to the duration and amount of smoking ('packyears'). 2. Radon is formed by radioactive decay of uranium, which is present in soil. i. Accumulates in closed spaces such as basements ii. Responsible for most of the public exposure to ionizing radiation; 2nd most frequent cause oflung carcinoma in US iii. Increased risk of lung cancer is also seen in uranium miners. 3. Environmental toxins include asbestos, coal fueled stoves, and metals (arsenic, chromium, and nickel) C. Presenting symptoms are nonspecific (e.g., cough, hemoptysis, dyspnea, weight loss, and post-obstructive pneumonia).


Pathoma_Husain

Pathoma_Husain. C. Presenting symptoms are nonspecific (e.g., cough, hemoptysis, dyspnea, weight loss, and post-obstructive pneumonia). D. Imaging usually reveals a large, spiculated mass; however, a solitary nodule ('coinlesion') can be seen. Biopsy is necessary for a diagnosis of cancer. 1. Benign lesions may also produce a 'coin-lesion,' especially in younger patients. Examples include i. Granuloma-often due to TB or fungus (especially Histoplasma in the Midwest) ii. Bronchial hamartoma-benign tumor composed oflung tissue and cartilage; often calcified on imaging E. Lung carcinoma is classically divided into 2 categories (Table 9.5). 1. 2. Table 9.5: Cancers of the Lung , , HISTOLOGY Poorly differentiated small cells (Fig. 9.19) differentiation, chromogranin positive Glands, mucin (Fig. 9.20A), or TTF- Keratin pearls, Squamous cell intercellular bridges carcinoma (Fig. 9.22A,B), or p40


Pathoma_Husain

Pathoma_Husain. Glands, mucin (Fig. 9.20A), or TTF- Keratin pearls, Squamous cell intercellular bridges carcinoma (Fig. 9.22A,B), or p40 Poorly differentiated Large cell large cells (no glands, neuroendocrine mucin, TTF-1, keratin carcinoma pearls, intercellular bridges, or p40) (nests); chromogranin positive (Fig. 9.23A,B) Most common sources Metastasis to lung are breast and colon carcinoma. Small cell carcinoma (15%)-usually not amenable to surgical resection (treated with chemotherapy and radiation) Non-small cell carcinoma (85%) i. Usually amenable to surgical resection ii. Major subtypes include adenocarcinoma (50%), squamous cell carcinoma (30%), large cell neuroendocrine carcinoma (5%), and carcinoid tumor (5%). Not significantly related to smoking Peripheral (Fig. 9.20B) Central (Fig. 9.22C) Central or peripheral; when central, classically forms a polyp-like mass in the bronchus (Fig. 9.23C)


Pathoma_Husain

Pathoma_Husain. Not significantly related to smoking Peripheral (Fig. 9.20B) Central (Fig. 9.22C) Central or peripheral; when central, classically forms a polyp-like mass in the bronchus (Fig. 9.23C) Rapid growth and early metastasis; may produce endocrine (e.g., ADH or ACTH) or nervous system (e.g., Lambert-Eaton myasthenic syndrome) paraneoplastic syndromes Adenocarcinoma in-situ exhibits columnar cells that grow along preexisting bronchioles and alveoli (Fig. 9.21); may present as pneumonia-like consolidation on imaging Diagnosis of exclusion Low-grade malignancy; rarely, can cause carcinoid syndrome Fig. 9.18 Granularity of lung, neonatal respiratory Fig. 9.19 Small cell carcinoma. distress syndrome. (Published with permission from LearningRadiology.com) I .. ·.°' Fig. 9.20 Adenocarcinoma. A, Gland formation and mucin production. B, Peripheral location. (B, Fig. 9.21 Adenocarcinoma in-situ. Courtesy ofThomas Krausz, MD)


Pathoma_Husain

Pathoma_Husain. I .. ·.°' Fig. 9.20 Adenocarcinoma. A, Gland formation and mucin production. B, Peripheral location. (B, Fig. 9.21 Adenocarcinoma in-situ. Courtesy ofThomas Krausz, MD) Fig . 9.22 Squamous cell carcinoma. A, Keratin pearls. B, lntercellular bridges. C, Central location. (B, Courtesy Thomas Krausz, MD. C, Courtesy of Yale Rosen, MD) Fig. 9.23 Carcinoid tumor. A, Microscopic appea rance. B, Chromogranin expression by immunohistochemistry. C, Polyp-like growth in the bronchus. (C, Courtesy of Ya le Rosen, MD) F. TNM staging 1. T-Tumor size and local extension i. Obstruction of SVC leads to distended head and neck veins with edema and blue discoloration of arms and face (superior vena cava syndrome).


Pathoma_Husain

Pathoma_Husain. F. TNM staging 1. T-Tumor size and local extension i. Obstruction of SVC leads to distended head and neck veins with edema and blue discoloration of arms and face (superior vena cava syndrome). ii. Involvement of recurrent laryngeal (hoarseness) or phrenic (diaphragmatic paralysis) nerve iii. Involvement of the sympathetic chain (ptosis, miosis, and anhidrosis; Horner syndrome) and brachia! plexus (shoulder pain and hand weakness) is seen with apical tumors involving the superior sulcus (Pancoast tumor) 2. N-spread to regional lymph nodes (hilar and mediastinal) 3. M-a unique site of distant metastasis is the adrenal gland. 4. Overall, 15% 5-year survival; lung carcinoma often presents late i. Screening by low-dose CT recommended for patients with long smoking history 5. i. EGFR mutations (erlotinib) or ALK translocation (crizotinib) may be present in adenocarcinoma; EGFR is especially common in Asian females who are non-smokers. 6.


Pathoma_Husain

Pathoma_Husain. i. EGFR mutations (erlotinib) or ALK translocation (crizotinib) may be present in adenocarcinoma; EGFR is especially common in Asian females who are non-smokers. 6. Testing for PD-Ll expression (pembrolizumab) guides immunotherapy in advanced disease; PD-Ll may be present in any non-small cell carcinoma. I. PNEUMOTHORAX A. Accumulation of air in the pleural space B. Spontaneous pneumothorax is due to rupture of an emphysematous bleb; seen in young adults 1. Results in collapse of a portion of the lung (Fig. 9.24); trachea shifts to the side of collapse. C. Tension pneumothorax arises with penetrating chest wall injury. 1. Air enters the pleural space, but cannot exit; trachea is pushed opposite to the side of injury. 2. Medical emergency; treated with insertion of a chest tube II. MESOTHELIOMA A. Malignant neoplasm of mesothelial cells; highly associated with occupational exposure to asbestos


Pathoma_Husain

Pathoma_Husain. 2. Medical emergency; treated with insertion of a chest tube II. MESOTHELIOMA A. Malignant neoplasm of mesothelial cells; highly associated with occupational exposure to asbestos B. Presents with recurrent pleural effusions, dyspnea, and chest pain; tumor encases the lung (Fig. 9.25). Fig. 9.24 Spontaneous pneumothorax. (Courtesy Fig. 9.25 Mesothelioma. (Courtesy of Jamie of James Heilman, MD, Wikiped ia.) Steinmetz, MD) I. CLEFT LIP AND PALATE A. Full-thickness defect of lip or palate (Fig. 10.1) B. Due to failure of facial prominences to fuse 1. During early pregnancy, facial prominences (one from superior, two from the sides, and two from inferior) grow and fuse together to form the face. C. Cleft lip and palate usually occur together; isolated cleft lip or palate is less common. II. APHTHOUS ULCER A. Painful, superficial ulceration of the oral mucosa (Fig. 10.2) B. Arises in relation to stress and resolves spontaneously, but often recurs


Pathoma_Husain

Pathoma_Husain. II. APHTHOUS ULCER A. Painful, superficial ulceration of the oral mucosa (Fig. 10.2) B. Arises in relation to stress and resolves spontaneously, but often recurs C. Characterized by a grayish base surrounded by erythema III. BEH<;:ET SYNDROME A. Recurrent aphthous ulcers, genital ulcers, and uveitis B. Due to immune complex vasculitis involving small vessels C. Can be seen after viral infection, but etiology is unknown IV. A. Vesicles involving oral mucosa that rupture, resulting in shallow, painful, red ulcers B. Usually due to HSV-1 C. Primary infection occurs in childhood; lesions heal, but virus remains dormant in ganglia of the trigeminal nerve. D. Stress and sunlight cause reactivation of the virus, leading to vesicles that often arise on the lips (cold sore, Fig. 10.3). V. A. Malignant neoplasm of squamous cells lining the oral mucosa B. Tobacco and alcohol are major risk factors. C. Floor of mouth is the most common location.


Pathoma_Husain

Pathoma_Husain. V. A. Malignant neoplasm of squamous cells lining the oral mucosa B. Tobacco and alcohol are major risk factors. C. Floor of mouth is the most common location. D. Oral leukoplakia and erythroplakia are precursor lesions. 1. Leukoplakia is a white plaque that cannot be scraped away; often represents squamous cell dysplasia 2. Leukoplakia is distinct from oral candidiasis (thrush) and hairy leukoplakia. i. Oral candidiasis is a white deposit on the tongue, which is easily scraped away (Fig. 10.4); usually seen in immunocompromised states ii. Hairy leukoplakia is a white, rough ('hairy') patch that arises on the lateral tongue. It is usually seen in immunocompromised individuals (e.g., AIDS) and is due to EBY-induced squamous cell hyperplasia; not pre-malignant 3. Erythroplakia (red plaque) represents vascularized leukoplakia and is highly suggestive of squamous cell dysplasia. 4. Erythroplakia and leukoplakia are often biopsied to rule out carcinoma. pathoma.com


Pathoma_Husain

Pathoma_Husain. 4. Erythroplakia and leukoplakia are often biopsied to rule out carcinoma. pathoma.com I. BASIC PRINCIPLES A. Salivary glands are exocrine glands that secrete saliva. B. Divided into major (parotid, submandibular, and sublingual glands) and minor glands (hundreds of microscopic glands distributed throughout the oral mucosa) II. MUMPS A. Infection with mumps virus resulting in bilateral inflamed parotid glands B. Orchitis, pancreatitis, and aseptic meningitis may also be present. 1. Serum amylase is increased due to salivary gland or pancreatic involvement. 2. Orchitis carries risk of sterility, especially in teenagers. III. SIALADENITIS A. Inflammation of the salivary gland B. Most commonly due to an obstructing stone (sialolithiasis) leading to Staphylococcus aureus infection; usually unilateral IV. A. Benign tumor composed of stromal (e.g., cartilage) and epithelial tissue; most common tumor of the salivary gland


Pathoma_Husain

Pathoma_Husain. IV. A. Benign tumor composed of stromal (e.g., cartilage) and epithelial tissue; most common tumor of the salivary gland B. Usually arises in parotid; presents as a mobile, painless, circumscribed mass at the angle of the jaw C. High rate of recurrence; extension of small islands of tumor through tumor capsule often leads to incomplete resection (Fig. 10.5). D. Rarely may transform into carcinoma, which presents with signs of facial nerve damage (facial nerve runs through parotid gland) V. A. Benign cystic tumor with abundant lymphocytes and germinal centers (lymph node-like stroma); 2nd most common tumor of the salivary gland B. Almost always arises in the parotid VI. MUCOEPIDERMOID CARCINOMA A. Malignant tumor composed of mucinous and squamous cells; most common malignant tumor of the salivary gland B. Usually arises in the parotid; commonly involves the facial nerve


Pathoma_Husain

Pathoma_Husain. A. Malignant tumor composed of mucinous and squamous cells; most common malignant tumor of the salivary gland B. Usually arises in the parotid; commonly involves the facial nerve Fig, 10,1 Cleft lip and palate. (Courtesy of James Fig. 10.2 Aphthous ulcer. (Reproduced from Fig, 10.3 Cold sore. (Courtesy of Dr. Herrmann, Heilman, MD, Wikipedia) wikipedia.org, CCBY-SA 3.0) CDC) I. TRACHEOESOPHAGEAL FISTULA A. Congenital defect resulting in a connection between the esophagus and trachea B. Most common variant consists of proximal esophageal atresia with the distal esophagus arising from the trachea (Fig. 10.6). 1. Presents with vomiting, polyhydramnios, abdominal distension, and aspiration II. ESOPHAGEAL WEB A. Thin protrusion of esophageal mucosa, most often in the upper esophagus B. Presents with dysphagia for poorly chewed food C. Increased risk for esophageal squamous cell carcinoma


Pathoma_Husain

Pathoma_Husain. A. Thin protrusion of esophageal mucosa, most often in the upper esophagus B. Presents with dysphagia for poorly chewed food C. Increased risk for esophageal squamous cell carcinoma D. Plummer-Vinson syndrome is characterized by severe iron deficiency anemia, esophageal web, and beefy-red tongue due to atrophic glossitis. III. ZENKER DIVERTICULUM A. Outpouching of pharyngeal mucosa through an acquired defect in the muscular wall (false diverticulum) B. Arises above the upper esophageal sphincter at the junction of the esophagus and pharynx C. Presents with dysphagia, obstruction, and halitosis (bad breath) IV. A. Longitudinal laceration of mucosa at the gastroesophageal (GE) junction B. Caused by severe vomiting, usually due to alcoholism or bulimia C. Presents with painful hematemesis D. Risk ofBoerhaave syndrome-rupture of esophagus leading to air in the mediastinum and subcutaneous emphysema V. A. Dilated submucosal veins in the lower esophagus


Pathoma_Husain

Pathoma_Husain. D. Risk ofBoerhaave syndrome-rupture of esophagus leading to air in the mediastinum and subcutaneous emphysema V. A. Dilated submucosal veins in the lower esophagus B. Arise secondary to portal hypertension 1. Distal esophageal vein normally drains into the portal vein via the left gastric vein. 2. In portal hypertension, the left gastric vein backs up into the esophageal vein, resulting in dilation (varices). C. Asymptomatic, but risk of rupture exists 1. Presents with painless hematemesis 2. Most common cause of death in cirrhosis Fig. 10.4 Oral candidiasis. (Courtesy of James Fig. 10.5 Pleomorphic adenoma. (Courtesy of Fig. 10.6 Tracheoesophageal fistula. (Courtesy of Heilman, MD, Wikipedia) Bu lent Celasun, MD) humpath.com) VI. ACHALASIA A. Disordered esophageal motility with inability to relax the lower esophageal sphincter (LES) B. Due to damaged ganglion cells in the myenteric plexus 1.


Pathoma_Husain

Pathoma_Husain. VI. ACHALASIA A. Disordered esophageal motility with inability to relax the lower esophageal sphincter (LES) B. Due to damaged ganglion cells in the myenteric plexus 1. Ganglion cells of myenteric plexus are located between the inner circular and outer longitudinal layers of the muscularis propria and are important for regulating bowel motility and relaxing the LES. 2. Damage to ganglion cells can be idiopathic or secondary to a known insult (e.g., Trypanosoma cruzi infection in Chagas disease). C. Clinical features 1. 2. 3. 4. 'Bird-beak' sign on barium swallow study (Fig. 10.7) 5. VII. GASTROESOPHAGEAL REFLUX DISEASE (GERD) A. Reflux of acid from the stomach due to reduced LES tone B. Risk factors include alcohol, tobacco, obesity, fat-rich diet, caffeine, and hiatal hernia. C. Clinical features 1. 2. 3. Damage to enamel ofteeth 4. Ulceration with stricture and Barrett esophagus are late complications. VIII. BARRETT ESOPHAGUS


Pathoma_Husain

Pathoma_Husain. C. Clinical features 1. 2. 3. Damage to enamel ofteeth 4. Ulceration with stricture and Barrett esophagus are late complications. VIII. BARRETT ESOPHAGUS A. Metaplasia of the lower esophageal mucosa from stratified squamous epithelium to nonciliated columnar epithelium with goblet cells (Fig. 10.8); seen in 10% of patients with GERD 1. Response oflower esophageal stem cells to acidic stress B. May progress to dysplasia and adenocarcinoma IX. ESOPHAGEAL CARCINOMA A. Subclassified as adenocarcinoma or squamous cell carcinoma B. Adenocarcinoma is a malignant proliferation of glands; most common type of esophageal carcinoma in the West 1. Arises from preexisting Barrett esophagus; usually involves the lower one-third of the esophagus Fig. 10.7 'Bird-beak' sign, achalasia. (Courtesy of Fig. 10.8 Barrett esophagus. F. Farrokhi, MD and M. Vaezi, MD)


Pathoma_Husain

Pathoma_Husain. Fig. 10.7 'Bird-beak' sign, achalasia. (Courtesy of Fig. 10.8 Barrett esophagus. F. Farrokhi, MD and M. Vaezi, MD) C. Squamous cell carcinoma is a malignant proliferation of squamous cells; most common esophageal cancer worldwide 1. Usually arises in upper or middle third of the esophagus; major risk factors include 1. Alcohol and tobacco (most common causes) ii. Very hot tea iii. Achalasia iv. Esophageal web (e.g., Plummer-Vinson syndrome) v. Esophageal injury (e.g., lye ingestion) D. Esophageal carcinoma presents late (poor prognosis). 1. Symptoms include progressive dysphagia (solids to liquids), weight loss, pain, and hematemesis. 2. Squamous cell carcinoma may additionally present with hoarse voice (recurrent laryngeal nerve involvement) and cough (tracheal involvement). E. Location oflymph node spread depends on the level of the esophagus that is involved. 1. 2. 3. I. GASTROSCHISIS


Pathoma_Husain

Pathoma_Husain. E. Location oflymph node spread depends on the level of the esophagus that is involved. 1. 2. 3. I. GASTROSCHISIS A. Congenital malformation of the anterior abdominal wall leading to exposure of abdominal contents (Fig. 10.9) II. OMPHALOCELE A. Persistent herniation of bowel into umbilical cord B. Due to failure of herniated intestines to return to the body cavity during development 1. Contents are covered by peritoneum and amnion of the umbilical cord (Fig. 10.10). III. PYLORIC STENOSIS A. Congenital hypertrophy of pyloric smooth muscle; more common in males B. Classically presents two weeks after birth as 1. 2. 3. Olive-like mass in the abdomen C. Treatment is myotomy. Fig. 10.9 Gastroschisis. (Courtesy of humpath. Fig.10.10 Omphalocele. (Courtesy of J.T. Stocker, Fig.10.11 Intestinal metaplasia, chronic gastritis. com) MD) IV. A. Acidic damage to the stomach mucosa


Pathoma_Husain

Pathoma_Husain. IV. A. Acidic damage to the stomach mucosa B. Due to imbalance between mucosa! defenses and acidic environment 1. Defenses include mucin layer produced by foveolar cells, bicarbonate secretion by surface epithelium, and normal blood supply (provides nutrients and picks up leaked acid). C. Risk factors 1. Severe burn (Curling ulcer)-Hypovolemia leads to decreased blood supply. 2. 3. 4. 5. Increased intracranial pressure (Cushing ulcer)-Increased stimulation ofvagus nerve leads to increased acid production. 6. Shock-Multiple (stress) ulcers may be seen in ICU patients. D. Acid damage results in superficial inflammation, erosion (loss of superficial epithelium), or ulcer (loss of mucosa! layer). V. A. Chronic inflammation of stomach mucosa B. Divided into two types based on underlying etiology: chronic autoimmune gastritis and chronic H pylori gastritis


Pathoma_Husain

Pathoma_Husain. V. A. Chronic inflammation of stomach mucosa B. Divided into two types based on underlying etiology: chronic autoimmune gastritis and chronic H pylori gastritis C. Chronic autoimmune gastritis is due to autoimmune destruction of gastric parietal cells, which are located in the stomach body and fundus. 1. Associated with antibodies against parietal cells and/or intrinsic factor; useful for diagnosis, but pathogenesis is mediated by T cells (type IV hypersensitivity) 2. i. Atrophy of mucosa with intestinal metaplasia (Fig. 10.11) ii. Achlorhydria with increased gastrin levels and antral G-cell hyperplasia iii. Megaloblastic (pernicious) anemia due to lack of intrinsic factor iv. Increased risk for gastric adenocarcinoma (intestinal type) D. Chronic H pylori gastritis is due to H pylori-induced acute and chronic inflammation; most common form of gastritis (90%) 1.


Pathoma_Husain

Pathoma_Husain. D. Chronic H pylori gastritis is due to H pylori-induced acute and chronic inflammation; most common form of gastritis (90%) 1. H pylori ureases and proteases along with inflammation weaken mucosa! defenses; antrum is the most common site (Fig. 10.12). 2. Presents with epigastric abdominal pain; increased risk for ulceration (peptic ulcer disease), gastric adenocarcinoma (intestinal type), and MALT lymphoma 3. Treatment involves triple therapy. i. Resolves gastritis/ulcer and reverses intestinal metaplasia ii. Negative urea breath test and lack of stool antigen confirm eradication of Hpylori. Fig. 10.12 H pylori. (Courtesy of Ed Uthman, MD) Fig. 10.13 Gastric ulcer. A, Peptic ulcer disease. B, Carcinoma. (Courtesy of Aliya Husain, MD) VI. PEPTIC ULCER DISEASE A. Solitary mucosa! ulcer involving proximal duodenum (90%) or distal stomach (10%) B. Duodenal ulcer is almost always due to H pylori (> 95%); rarely, may be due to ZE syndrome 1.


Pathoma_Husain

Pathoma_Husain. A. Solitary mucosa! ulcer involving proximal duodenum (90%) or distal stomach (10%) B. Duodenal ulcer is almost always due to H pylori (> 95%); rarely, may be due to ZE syndrome 1. Presents with epigastric pain that improves with meals 2. Diagnostic endoscopic biopsy shows ulcer with hypertrophy of Brunner glands. 3. Usually arises in anterior duodenum; when present in posterior duodenum, rupture may lead to bleeding from the gastroduodenal artery or acute pancreatitis C. Gastric ulcer is usually due to H pylori (75%); other causes include NSAIDs and bile reflux. 1. Presents with epigastric pain that worsens with meals 2. Ulcer is usually located on the lesser curvature of the antrum. 3. Rupture carries risk of bleeding from left gastric artery. D. Differential diagnosis of ulcers includes carcinoma. 1. Duodenal ulcers are almost never malignant (duodenal carcinoma is extremely rare). 2. Gastric ulcers can be caused by gastric carcinoma (intestinal subtype).


Pathoma_Husain

Pathoma_Husain. 1. Duodenal ulcers are almost never malignant (duodenal carcinoma is extremely rare). 2. Gastric ulcers can be caused by gastric carcinoma (intestinal subtype). i. Benign peptic ulcers are usually small (< 3 cm), sharply demarcated ("punched-out"), and surrounded by radiating folds of mucosa (Fig. 10.13A). 11. Malignant ulcers are large and irregular with heaped up margins (Fig. 10.13B) iii. Biopsy is required for definitive diagnosis. VII. GASTRIC CARCINOMA A. Malignant proliferation of surface epithelial cells (adenocarcinoma) B. Subclassified into intestinal and diffuse types C. Intestinal type (more common) presents as a large, irregular ulcer with heaped up margins; most commonly involves the lesser curvature of the antrum (similar to gastric ulcer) 1. Risk factors include intestinal metaplasia (e.g., due to H pylori and autoimmune gastritis), nitrosamines in smoked foods (Japan), and blood type A.


Pathoma_Husain

Pathoma_Husain. D. Diffuse type is characterized by signet ring cells that diffusely infiltrate the gastric wall (Fig. 10.14B); desmoplasia results in thickening of stomach wall (linitis plastica, Fig. 10.14A). 1. Not associated with H pylori, intestinal metaplasia, or nitrosamines E. Gastric carcinoma presents late with weight loss, abdominal pain, anemia, and early satiety; rarely presents as acanthosis nigricans or Leser-Trelat sign F. Spread to lymph nodes can involve the left supraclavicular node (Virchow node). G. Distant metastasis most commonly involves liver; other sites include 1. Periumbilical region (Sister Mary Joseph nodule); seen with intestinal type Fig. 10.14 Gastric carcinoma, diffuse type. A, Linitis plastica. B, Signet-ring cells. (A, Courtesy of Ed Uthman, MD) 2. Bilateral ovaries (Krukenberg tumor); seen with diffuse type I. DUODENAL ATRESIA A. Congenital failure of duodenum to canalize; associated with Down syndrome B. Clinical features 1. 2.


Pathoma_Husain

Pathoma_Husain. I. DUODENAL ATRESIA A. Congenital failure of duodenum to canalize; associated with Down syndrome B. Clinical features 1. 2. Distension of stomach and blind loop of duodenum ('double bubble' sign, Fig. 10.15) 3. II. MECKEL DIVERTICULUM A. Outpouching of all three layers of the bowel wall (true diverticulum, Fig. 10.16) B. Arises due to failure of the vitelline duct to involute C. 'Rule of 2s' 1. Seen in 2% of the population (most common congenital anomaly of the GI tract) 2. 2 inches long and located in the small bowel within 2 feet of the ileocecal valve 3. Can present during the first 2 years of life with bleeding (due to heterotopic gastric mucosa), volvulus, intussusception, or obstruction (mimics appendicitis); however, most cases are asymptomatic. III. VOLVULUS A. Twisting of bowel along its mesentery B. Results in obstruction and disruption of the blood supply with infarction (Fig. 10.17)


Pathoma_Husain

Pathoma_Husain. III. VOLVULUS A. Twisting of bowel along its mesentery B. Results in obstruction and disruption of the blood supply with infarction (Fig. 10.17) C. Most common locations are sigmoid colon (elderly) and cecum (young adults). IV. A. Telescoping of proximal segment of bowel forward into distal segment 1. Telescoped segment is pulled forward by peristalsis, resulting in obstruction and disruption of blood supply with infarction. B. Associated with a leading edge (focus of traction) 1. In children, the most common cause is lymphoid hyperplasia (e.g., due to rotavirus); usually arises in the terminal ileum, leading to intussusception into the cecum 2. In adults, the most common cause is tumor. V. A. Small bowel is highly susceptible to ischemic injury. 1. Transmural infarction occurs with thrombosis/embolism of the superior mesenteric artery or thrombosis of the mesenteric vein. 2. Mucosa! infarction occurs with marked hypotension.


Pathoma_Husain

Pathoma_Husain. 1. Transmural infarction occurs with thrombosis/embolism of the superior mesenteric artery or thrombosis of the mesenteric vein. 2. Mucosa! infarction occurs with marked hypotension. B. Clinical features include abdominal pain, bloody diarrhea, and decreased bowel sounds. VI. LACTOSE INTOLERANCE A. Decreased function of the lactase enzyme found in the brush border of enterocytes 1. Lactase normally breaks down lactose into glucose and galactose. B. Presents with abdominal distension and diarrhea upon consumption of milk products; undigested lactose is osmotically active. C. Deficiency may be congenital (rare autosomal recessive disorder) or acquired (often develops in late childhood); temporary deficiency is seen after small bowel infection (]actase is highly susceptible to injury). VII. CELIAC DISEASE A. Immune-mediated damage of small bowel villi due to gluten exposure; associated with HLA-DQ2 and DQS


Pathoma_Husain

Pathoma_Husain. VII. CELIAC DISEASE A. Immune-mediated damage of small bowel villi due to gluten exposure; associated with HLA-DQ2 and DQS B. Gluten is present in wheat and grains; its most pathogenic component is gliadin. 1. Once absorbed, gliadin is deamidated by tissue transglutaminase (tTG). 2. Deamidated gliadin is presented by antigen presenting cells via MHC class II. 3. Helper T cells mediate tissue damage. C. Clinical presentation 1. Children classically present with abdominal distension, diarrhea, and failure to thrive. 2. Adults classically present with chronic diarrhea and bloating. 3. Small, herpes-like vesicles may arise on skin (dermatitis herpetiformis). Due to IgA deposition at the tips of dermal papillae; resolves with gluten-free diet D. Laboratory findings 1.


Pathoma_Husain

Pathoma_Husain. 3. Small, herpes-like vesicles may arise on skin (dermatitis herpetiformis). Due to IgA deposition at the tips of dermal papillae; resolves with gluten-free diet D. Laboratory findings 1. IgA antibodies against endomysium, tTG, or gliadin; IgG antibodies are also present and are useful for diagnosis in individuals with IgA deficiency (increased incidence ofigA deficiency is seen in celiac disease). 2. Duodenal biopsy reveals flattening of villi, hyperplasia of crypts, and increased intraepithelial lymphocytes (Fig. 10.18). Damage is most prominent in the duodenum; jejunum and ileum are less involved. E. Symptoms resolve with gluten-free diet. 1. Small bowel carcinoma and T-cell lymphoma are late complications that present as refractory disease despite good dietary control. Fig. 10.18 Celiac disease. A, Flattened villi. B, Normal villi for comparison. VIII.TROPICAL SPRUE A. Damage to small bowel villi due to an unknown organism resulting in malabsorption


Pathoma_Husain

Pathoma_Husain. Fig. 10.18 Celiac disease. A, Flattened villi. B, Normal villi for comparison. VIII.TROPICAL SPRUE A. Damage to small bowel villi due to an unknown organism resulting in malabsorption B. Similar to celiac disease except 1. Occurs in tropical regions (e.g., Caribbean) 2. Arises after infectious diarrhea and responds to antibiotics 3. Damage is most prominent in jejunum and ileum (secondary vitamin B12 or folate deficiency may ensue); duodenum is less commonly involved. IX. A. Systemic tissue damage characterized by macrophages loaded with Tropheryma whippelii organisms; partially destroyed organisms are present in macrophage lysosomes (positive for PAS). B. Classic site of involvement is the small bowel lamina propria (Fig. 10.19). 1. Macrophages compress lacteals. 2. Chylomicrons cannot be transferred from enterocytes to lymphatics. 3. C. Other common sites ofinvolvement include synovium ofjoints (arthritis), cardiac valves, lymph nodes, and CNS. X.


Pathoma_Husain

Pathoma_Husain. 2. Chylomicrons cannot be transferred from enterocytes to lymphatics. 3. C. Other common sites ofinvolvement include synovium ofjoints (arthritis), cardiac valves, lymph nodes, and CNS. X. A. Autosomal recessive deficiency of apolipoprotein B-48 and B-100 B. Clinical features 1. Malabsorption-due to defective chylomicron formation (requires B-48) 2. XI. CARCINOID TUMOR A. Malignant proliferation of neuroendocrine cells; low-grade malignancy 1. Tumor cells contain neurosecretory granules that are positive for chromogranin. B. Can arise anywhere along the gut; small bowel is the most common site. 1. Grows as a submucosal polyp-like nodule (Fig. 10.20) C. Often secretes serotonin 1. Serotonin is released into the portal circulation and metabolized by liver monoamine oxidase (MAO) into 5-HIAA. 2. 5-HIAA is excreted in the urine. D. Metastasis of carcinoid tumor to the liver allows serotonin to bypass liver metabolism.


Pathoma_Husain

Pathoma_Husain. 2. 5-HIAA is excreted in the urine. D. Metastasis of carcinoid tumor to the liver allows serotonin to bypass liver metabolism. 1. Serotonin is released into the hepatic vein and leaks into systemic circulation via hepato-systemic shunts, resulting in carcinoid syndrome and carcinoid heart disease. Fig. 10.19 Whipple disease. A, Macrophages within lamina propria of small bowel villi. B, Twhippelii Fig. 10.20 Carcinoid tumor. organisms highlighted by PAS stain. 2. Carcinoid syndrome is characterized by bronchospasm, diarrhea, and flushing of skin; symptoms can be triggered by alcohol or emotional stress, which stimulate serotonin release from the tumor. 3. Carcinoid heart disease is characterized by right-sided valvular fibrosis (increased collagen) leading to tricuspid regurgitation and pulmonary valve stenosis; left-sided valvular lesions are not seen due to presence of monoamine oxidase (metabolizes serotonin) in the lung. I. ACUTE APPENDICITIS


Pathoma_Husain

Pathoma_Husain. I. ACUTE APPENDICITIS A. Acute inflammation of the appendix; most common cause of acute abdomen B. Related to obstruction of the appendix by lymphoid hyperplasia (children) or a fecalith (adults) C. Clinical features include 1. Periumbilical pain, fever, and nausea; pain eventually localizes to right lower quadrant (McBurney point). 2. Rupture results in peritonitis that presents with guarding and rebound tenderness. 3. Periappendiceal abscess is a common complication. I. BASIC PRINCIPLES A. Chronic, relapsing inflammation of bowel B. Possibly due to abnormal immune response to enteric flora C. Classically presents in young women (teens to 30s) as recurrent bouts of bloody diarrhea and abdominal pain 1. More prevalent in the West, particularly in Caucasians and Eastern European Jews D. Diagnosis of exclusion; symptoms mimic other causes of bowel inflammation (e.g., infection). E. Subclassified as ulcerative colitis or Crohn disease (Table 10.1) I. HIRSCHSPRUNG DISEASE


Pathoma_Husain

Pathoma_Husain. D. Diagnosis of exclusion; symptoms mimic other causes of bowel inflammation (e.g., infection). E. Subclassified as ulcerative colitis or Crohn disease (Table 10.1) I. HIRSCHSPRUNG DISEASE A. Defective relaxation and peristalsis of rectum and distal sigmoid colon 1. Associated with Down syndrome B. Due to congenital failure of ganglion cells (neural crest-derived) to descend into myenteric and submucosal plexus 1. Myenteric (Auerbach) plexus is located between the inner circular and outer longitudinal muscle layers of the muscularis propria and regulates motility. 2. Submucosal (Meissner) plexus is located in the submucosa and regulates blood flow, secretions, and absorption. C. Clinical features are based on obstruction. 1. Failure to pass meconium 2. 3. Massive dilatation (megacolon) of bowel proximal to obstruction with risk for rupture D. Rectal suction biopsy reveals lack of ganglion cells.


Pathoma_Husain

Pathoma_Husain. 1. Failure to pass meconium 2. 3. Massive dilatation (megacolon) of bowel proximal to obstruction with risk for rupture D. Rectal suction biopsy reveals lack of ganglion cells. E. Treatment involves resection of the involved bowel; ganglion cells are present in the bowel proximal to the diseased segment. Table 10.1: Main Features of Ulcerative Colitis and Crohn Disease Begins in rectum and can extend proximally up to the cecum (involvement is continuous, Fig. 10.21A); remainder of the GI tract is unaffected. Left lower quadrant pain (rectum) with bloody diarrhea Crypt abscesses with neutrophils (Fig. 10.21B) Pseudopolyps; loss ofhaustra ('lead pipe' sign on imaging, Fig. 10.21C) Toxic megacolon and carcinoma (risk is based on extent of colonic involvement and duration of disease; generally not a concern until > 10 years of disease) CROHN DISEASE Full-thickness inflammation with knife-like fissures


Pathoma_Husain

Pathoma_Husain. Full-thickness inflammation with knife-like fissures Anywhere from mouth to anus with skip lesions; terminal ileum is the most common site, rectum is least common. Right lower quadrant pain (ileum) with nonbloody diarrhea Lymphoid aggregates with granulomas (40% of cases) Cobblestone mucosa (Fig. 10.22A), creeping fat, and strictures ('string-sign' on imaging, Fig. 10.22B) Malabsorption with nutritional deficiency, calcium oxalate nephrolithiasis, fistula formation, and carcinoma, if colonic disease is present Arthritis (peripheral joints, ankylosing spondylitis, sacroiliitis, migratory polyarthritis), uveitis, erythema nodosum (Fig. 10.22C), pyoderma gangrenosum, primary sclerosing cholangitis, and p-ANCA Fig. 10.21 Ulcerative colitis. A, Gross appearance. B, Crypt abscess. C, 'Lead pipe' sign (A, Courtesy of Jamie Steinmetz, MD. C, Published with permission from LearningRadiology.com)


Pathoma_Husain

Pathoma_Husain. Fig. 10.21 Ulcerative colitis. A, Gross appearance. B, Crypt abscess. C, 'Lead pipe' sign (A, Courtesy of Jamie Steinmetz, MD. C, Published with permission from LearningRadiology.com) Fig. 10.22 Crohn disease. A, Cobblestone mucosa with stricture. B, 'String' sign. (A, Courtesy of Fig. 10.22C Erythema nodosum. humpath.com. B, Published with permission from LearningRadiology.com) II. COLONIC DIVERTICULA A. Outpouchings of mucosa and submucosa through the muscularis propria (Fig. 10.23, false diverticulum) B. Related to wall stress 1. Associated with constipation, straining, and low-fiber diet; commonly seen in older adults (risk increases with age) 2. Arise where the vasa recta traverse the muscularis propria (weak point in colonic wall); sigmoid colon is the most common location. C. Usually asymptomatic; complications include 1. 2. Diverticulitis-due to obstructing fecal material; presents with appendicitis-like symptoms in the left lower quadrant 3.


Pathoma_Husain

Pathoma_Husain. C. Usually asymptomatic; complications include 1. 2. Diverticulitis-due to obstructing fecal material; presents with appendicitis-like symptoms in the left lower quadrant 3. Fistula-Inflamed diverticulum ruptures and attaches to a local structure. Colovesicular fistula presents with air (or stool) in urine. III. ANGIODYSPLASIA A. Acquired malformation of mucosa! and submucosal capillary beds B. Usually arises in the cecum and right colon due to high wall tension C. Rupture classically presents as hematochezia in an older adult. IV. A. Autosomal dominant disorder resulting in thin-walled blood vessels, especially in the mouth and GI tract (Fig. 10.24) B. Rupture presents as bleeding. V. A. Ischemic damage to the colon, usually at the splenic flexure (watershed area of superior mesenteric artery [SMA]) B. Atherosclerosis of SMA is the most common cause. C. Presents with postprandial pain and weight loss; infarction results in pain and bloody diarrhea.


Pathoma_Husain

Pathoma_Husain. B. Atherosclerosis of SMA is the most common cause. C. Presents with postprandial pain and weight loss; infarction results in pain and bloody diarrhea. VI. IRRITABLE BOWEL SYNDROME A. Relapsing abdominal pain with bloating, flatulence, and change in bowel habits (diarrhea or constipation) that improves with defecation; classically seen in middleaged females B. Related to disturbed intestinal motility; no identifiable pathologic changes C. Increased dietary fiber may improve symptoms. Fig. 10.23 Colonic diverticula. A, Gross appearance. B, Microscopic appearance. Fig. 10.24 Hereditary hemorrhagic telangiectasia. (Courtesy of Ors. H. Fred and H. van Dijk, Images ofMemorable Cases) VII. COLONIC POLYPS A. Raised protrusions of colonic mucosa B. Most common types are hyperplastic and adenomatous polyps.


Pathoma_Husain

Pathoma_Husain. VII. COLONIC POLYPS A. Raised protrusions of colonic mucosa B. Most common types are hyperplastic and adenomatous polyps. 1. Hyperplastic polyps are due to hyperplasia of glands; classically show a 'serrated' appearance on microscopy i. Most common type of polyp; usually arise in the left colon (rectosigmoid) ii. Benign, with no malignant potential 2. Adenomatous polyps are due to neoplastic proliferation of glands (Fig. 10.25); 2nd most common type of colonic polyp i. Benign, but premalignant; may progress to adenocarcinoma via the adenoma-carcinoma sequence 3. Adenoma-carcinoma sequence describes the molecular progression from normal colonic mucosa to adenomatous polyp to carcinoma. i. APC (adenomatous polyposis coli gene) mutations (sporadic or germline) increase risk for formation of polyp. ii. K-ras mutation leads to formation of polyp.


Pathoma_Husain

Pathoma_Husain. i. APC (adenomatous polyposis coli gene) mutations (sporadic or germline) increase risk for formation of polyp. ii. K-ras mutation leads to formation of polyp. iii. p53 mutation and increased expression of COX allow for progression to carcinoma; aspirin impedes progression from adenoma to carcinoma. C. Screening for polyps is performed by colonoscopy and testing for fecal occult blood; polyps are usually clinically silent, but can bleed. 1. Goal is to remove adenomatous polyps before progression to carcinoma. D. On colonoscopy, hyperplastic and adenomatous polyps look identical. Hence, all polyps are removed and examined microscopically. 1. Greatest risk for progression from adenoma to carcinoma is related to size > 2 cm, sessile growth, and villous histology. VIII. FAMILIAL ADENOMATOUS POLYPOSIS (FAP) A. Autosomal dominant disorder characterized by 100s to 1000s of adenomatous colonic polyps (Fig. 10.26)


Pathoma_Husain

Pathoma_Husain. VIII. FAMILIAL ADENOMATOUS POLYPOSIS (FAP) A. Autosomal dominant disorder characterized by 100s to 1000s of adenomatous colonic polyps (Fig. 10.26) B. Due to inherited APC mutation (chromosome 5); increases propensity to develop adenomatous polyps throughout colon and rectum C. Colon and rectum are removed prophylactically; otherwise, almost all patients develop carcinoma by 40 years of age. D. Gardner syndrome is FAP with fibromatosis and osteomas. 1. Fibromatosis is a non-neoplastic proliferation of fibroblasts; arises in retroperitoneum (desmoid) and locally destroys tissue 2. Osteoma is a benign tumor of bone that usually arises in the skull. E. Turcot syndrome is FAP with CNS tumors (medulloblastoma and glial tumors). Fig. 10.25 Adenomatous polyp. Fig. 10.26 Familial adenomatous polyposis. (Courtesy of hum path.com) IX. A. Sporadic, hamartomatous (benign) polyp that arises in children(< 5 years) 1. Usually presents as a solitary rectal polyp that prolapses and bleeds


Pathoma_Husain

Pathoma_Husain. IX. A. Sporadic, hamartomatous (benign) polyp that arises in children(< 5 years) 1. Usually presents as a solitary rectal polyp that prolapses and bleeds B. Juvenile polyposis is characterized by multiple juvenile polyps in the stomach and colon; large numbers ofjuvenile polyps increase the risk of progression to carcinoma. X. A. Hamartomatous (benign) polyps throughout GI tract and mucocutaneous hyperpigmentation (freckle-like spots) on lips, oral mucosa, and genital skin; autosomal dominant disorder B. Increased risk for colorectal, breast, and gynecologic cancer XI. COLORECTAL CARCINOMA A. Carcinoma arising from colonic or rectal mucosa; 3rd most common site of cancer and 3rd most common cause of cancer-related death 1. Peak incidence is 60-70 years of age. B. Most commonly arises from adenoma-carcinoma sequence; a second important molecular pathway is microsatellite instability (MSI). 1.


Pathoma_Husain

Pathoma_Husain. B. Most commonly arises from adenoma-carcinoma sequence; a second important molecular pathway is microsatellite instability (MSI). 1. Microsatellites are repeating sequences of noncoding DNA; integrity of sequence (stability) is maintained during cell division. 2. Instability indicates defective DNA copy mechanisms (e.g., DNA mismatch repair enzymes). 3. Hereditary nonpolyposis colorectal carcinoma (HNPCC) is due to inherited mutations in DNA mismatch repair enzymes. i. Increased risk for colorectal, ovarian, and endometrial carcinoma ii. Colorectal carcinoma arises de novo (not from adenomatous polyps) at a relatively early age; usually right-sided C. Screening for colorectal carcinoma occurs via colonoscopy and fecal occult blood testing; begins at 50 years of age 1. Goal is to remove adenomatous polyps before carcinoma develops and to detect cancer early (before clinical symptoms arise). D. Carcinoma can develop anywhere along entire length of colon. 1.


Pathoma_Husain

Pathoma_Husain. D. Carcinoma can develop anywhere along entire length of colon. 1. Left-sided carcinoma usually grows as a 'napkin-ring' lesion; presents with decreased stool caliber, left lower quadrant pain, and blood-streaked stool 2. Right-sided carcinoma usually grows as a raised lesion; presents with irondeficiency anemia (occult bleeding) and vague pain. An older adult with iron deficiency anemia has colorectal carcinoma until proven otherwise. E. Colonic carcinoma is associated with an increased risk for Streptococcus bovis endocarditis. F. Staging 1. T-depth of invasion; tumors limited to the mucosa generally do not spread due to lack of lymphatics in the mucosa. 2. N-spread to regional lymph nodes 3. M-distant spread; most commonly involves the liver G. CEA is a serum tumor marker that is useful for assessing treatment response and detecting recurrence; not useful for screening Exocrine Pancreas, Gallbladder, and I. ANNULAR PANCREAS


Pathoma_Husain

Pathoma_Husain. G. CEA is a serum tumor marker that is useful for assessing treatment response and detecting recurrence; not useful for screening Exocrine Pancreas, Gallbladder, and I. ANNULAR PANCREAS A. Developmental malformation in which the pancreas forms a ring around the duodenum; risk of duodenal obstruction II. ACUTE PANCREATITIS A. Inflammation and hemorrhage of the pancreas B. Due to autodigestion of pancreatic parenchyma by pancreatic enzymes 1. Premature activation of trypsin leads to activation of other pancreatic enzymes. C. Results in liquefactive hemorrhagic necrosis of the pancreas and fat necrosis of the peripancreatic fat (Fig. 11.1) D. Most commonly due to alcohol and gallstones; other causes include trauma, hypercalcemia, hyperlipidemia, drugs, scorpion stings, mumps, and rupture of a posterior duodenal ulcer. E. Clinical features 1. Epigastric abdominal pain that radiates to the back 2. 3.


Pathoma_Husain

Pathoma_Husain. E. Clinical features 1. Epigastric abdominal pain that radiates to the back 2. 3. Periumbilical and flank hemorrhage (necrosis spreads into the periumbilical soft tissue and retroperitoneum) 4. Elevated serum lipase and amylase; lipase is more specific for pancreatic damage. 5. Hypocalcemia (calcium is consumed during saponification in fat necrosis) F. Complications 1. Shock-due to peripancreatic hemorrhage and fluid sequestration 2. i. Presents as an abdominal mass with persistently elevated serum amylase ii. Rupture is associated with release ofenzymes into the abdominal cavity and hemorrhage. 3. Pancreatic abscess-often due to E coli; presents with abdominal pain, high fever, and persistently elevated amylase 4. III. CHRONIC PANCREATITIS A. Fibrosis ofpancreatic parenchyma, most often secondary to recurrent acute pancreatitis 1. Most commonly due to alcohol (adults) and cystic fibrosis (children); however, many cases are idiopathic. B. Clinical features 1.


Pathoma_Husain

Pathoma_Husain. B. Clinical features 1. Epigastric abdominal pain that radiates to the back 2. Pancreatic insufficiency-results in malabsorption with steatorrhea and fatsoluble vitamin deficiencies. Amylase and lipase are not useful serologic markers ofchronic pancreatitis. 3. Dystrophic calcification of pancreatic parenchyma on imaging; contrast studies reveal a 'chain oflakes' pattern due to dilatation of pancreatic ducts. pathoma.com 4. Secondary diabetes mellitus-late complication due to destruction of islets 5. IV. PANCREATIC CARCINOMA A. Adenocarcinoma arising from the pancreatic ducts 1. Most commonly seen in the elderly (average age is 70 years) B. Major risk factors are smoking and chronic pancreatitis. C. Clinical features (usually occur late in disease) 1. 2. Obstructive jaundice with pale stools and palpable gallbladder; associated with tumors that arise in the head of the pancreas (most common location) 3.


Pathoma_Husain

Pathoma_Husain. 2. Obstructive jaundice with pale stools and palpable gallbladder; associated with tumors that arise in the head of the pancreas (most common location) 3. Secondary diabetes mellitus; associated with tumors that arise in the body or tail 4. 5. Migratory thrombophlebitis (Trousseau syndrome); presents as swelling, erythema, and tenderness in the extremities (seen in 10% of patients) 6. Serum tumor marker is CA 19-9. D. Surgical resection involves en bloc removal of the head and neck of pancreas, proximal duodenum, and gallbladder (Whipple procedure). E. Very poor prognosis; I-year survival is < 10%. I. BILIARY ATRESIA A. Failure to form or early destruction of extrahepatic biliary tree B. Leads to biliary obstruction within the first 2 months of life C. Presents with jaundice and progresses to cirrhosis II. CHOLELITHIASIS (GALLSTONES) A. Solid, round stones in the gallbladder


Pathoma_Husain

Pathoma_Husain. B. Leads to biliary obstruction within the first 2 months of life C. Presents with jaundice and progresses to cirrhosis II. CHOLELITHIASIS (GALLSTONES) A. Solid, round stones in the gallbladder B. Due to precipitation of cholesterol (cholesterol stones) or bilirubin (bilirubin stones) in bile 1. Arises with (1) supersaturation of cholesterol or bilirubin, (2) decreased phospholipids (e.g., lecithin) or bile acids (normally increase solubility), or (3) stasis C. Cholesterol stones (yellow) are the most common type (90%), especially in the West (Fig. 11.2A). 1. Usually radiolucent (10% are radiopaque due to associated calcium) 2. Risk factors include age (40s), estrogen (female gender, obesity, multiple pregnancies and oral contraceptives), clofibrate, Native American ethnicity, Crohn disease, and cirrhosis.


Pathoma_Husain

Pathoma_Husain. Risk factors include age (40s), estrogen (female gender, obesity, multiple pregnancies and oral contraceptives), clofibrate, Native American ethnicity, Crohn disease, and cirrhosis. Fig. 11.1 Acute pancreatitis. (Courtesy of Fig. 11.2 Gallstones. A, Cholesterol stones. B, Bilirubin stones. (A, Courtesy of K.V. Santosh, MD. B, hum path.com) Courtesy of humpath.com) Exocrine Pancreas, Gallbladder, and Liver Pathology D. Bilirubin stones (pigmented) are composed ofbilirubin (Fig. 11.2B). 1. 2. Risk factors include extravascular hemolysis (increased bilirubin in bile) and biliary tract infection (e.g., E coli, Ascaris lumbricoides, and Clonorchis sinensis).


Pathoma_Husain

Pathoma_Husain. 1. 2. Risk factors include extravascular hemolysis (increased bilirubin in bile) and biliary tract infection (e.g., E coli, Ascaris lumbricoides, and Clonorchis sinensis). i. Ascaris lumbricoides is a common roundworm that infects 25% of the world's population, especially in areas with poor sanitation (fecal-oral transmission); infects the biliary tract, increasing the risk for gallstones ii. Clonorchis sinensis is endemic in China, Korea, and Vietnam (Chinese liver fluke); infects the biliary tract, increasing the risk for gallstones, cholangitis, and cholangiocarcinoma E. Gallstones are usually asymptomatic; complications include biliary colic, acute and chronic cholecystitis, ascending cholangitis, gallstone ileus, and gallbladder cancer. III. BILIARY COLIC A. Waxing and waning right upper quadrant pain B. Due to the gallbladder contracting against a stone lodged in the cystic duct C. Symptoms are relieved if the stone passes.


Pathoma_Husain

Pathoma_Husain. III. BILIARY COLIC A. Waxing and waning right upper quadrant pain B. Due to the gallbladder contracting against a stone lodged in the cystic duct C. Symptoms are relieved if the stone passes. D. Common bile duct obstruction may result in acute pancreatitis or obstructive jaundice. IV. A. Acute inflammation of the gallbladder wall B. Impacted stone in the cystic duct results in dilatation with pressure ischemia, bacterial overgrowth (E coli), and inflammation. C. Presents with right upper quadrant pain, often radiating to right scapula, fever with t WBC count, nausea, vomiting, and t serum alkaline phosphatase (from duct damage) D. Risk of rupture ifleft untreated V. A. Chronic inflammation of the gallbladder B. Due to chemical irritation from longstanding cholelithiasis, with or without superimposed bouts of acute cholecystitis C. Characterized by herniation of gallbladder mucosa into the muscular wall (Rokitansky-Aschoff sinus, Fig. 11.3A)


Pathoma_Husain

Pathoma_Husain. C. Characterized by herniation of gallbladder mucosa into the muscular wall (Rokitansky-Aschoff sinus, Fig. 11.3A) D. Presents with vague right upper quadrant pain, especially after eating E. Porcelain gallbladder is a late complication (Fig. 11.3B). 1. Shrunken, hard gallbladder due to chronic inflammation, fibrosis, and dystrophic calcification :~7~/ ·'~{~. . . t1 ..•'-·.,_ :",A~?·'\),:~;,.:;,,;_ Fig. 11.3 Chronic cholecystitis. A, Rokitansky-Aschoff sinus. B, Porcelain ga ll bladder. (B, Courtesy of Drs. H. Fred and H. van Dijk, Images ofMemorable Cases) 2. Increased risk for carcinoma F. Treatment is cholecystectomy, especially if porcelain gallbladder is present. VI. ASCENDING CHOLANGITIS A. Bacterial infection of the bile ducts B. Usually due to ascending infection with enteric gram-negative bacteria C. Presents as sepsis (high fever and chills), jaundice, and abdominal pain D. Increased incidence with choledocholithiasis (stone in biliary ducts)


Pathoma_Husain

Pathoma_Husain. C. Presents as sepsis (high fever and chills), jaundice, and abdominal pain D. Increased incidence with choledocholithiasis (stone in biliary ducts) VII. GALLSTONE ILEUS A. Gallstone enters and obstructs the small bowel B. Due to cholecystitis with fistula formation between the gallbladder and small bowel VIII.GALLBLADDER CARCINOMA A. Adenocarcinoma arising from the glandular epithelium that lines the gallbladder wall (Fig. 11.4) B. Gallstones are a major risk factor, especially when complicated by porcelain gallbladder. C. Classically presents as cholecystitis in an elderly woman D. Poor prognosis I. JAUNDICE A. Yellow discoloration of the skin (Fig. 11.5); earliest sign is scleral icterus (yellow discoloration of the sclera). B. Due to t serum bilirubin, usually > 2.5 mg/dL C. Arises with disturbances in bilirubin metabolism (Table 11.1) D. Normal bilirubin metabolism 1. RBCs are consumed by macrophages of the reticuloendothelial system. 2.


Pathoma_Husain

Pathoma_Husain. C. Arises with disturbances in bilirubin metabolism (Table 11.1) D. Normal bilirubin metabolism 1. RBCs are consumed by macrophages of the reticuloendothelial system. 2. Protoporphyrin (from heme) is converted to unconjugated bilirubin (UCB). 3. Albumin carries UCB to the liver. 4. Uridine glucuronyl transferase (UGT) in hepatocytes conjugates bilirubin. 5. Conjugated bilirubin (CB) is transferred to bile canaliculi to form bile, which is stored in the gallbladder. 6. Bile is released into the small bowel to aid in digestion. 7. Intestinal flora convert CB to urobilinogen, which is oxidized to stercobilin (makes stool brown) and urobilin (partially reabsorbed into blood and filtered by kidney, making urine yellow). Fig.11 .4 Gallbladder carcinoma. (Courtesy of K.V. Fig. 11.5 Jaundice. (Courtesy of James Heilman, Fig. 11 .6 Acute hepatitis. Santosh, MD) MD, Wikipedia) Exocrine Pancreas, Gallbladder, and Liver Pathology Table 11.1: Causes of Jaundice


Pathoma_Husain

Pathoma_Husain. Exocrine Pancreas, Gallbladder, and Liver Pathology Table 11.1: Causes of Jaundice Physiologic jaundice of the newborn High levels of UCB overwhelm the conjugating ability of the liver. Newborn liver has transiently low UGT activity. Associated with gallstones, pancreatic carcinoma, cholangiocarcinoma, parasites, and liver fluke Inflammation disrupts hepatocytes and small bile ductules. t CB, ..J.. urine urobilinogen, and t alkaline phosphatase Table 11.2: Important Features of Hepatitis Viruses HAV is commonly acquired by travelers. HEV is commonly acquired from contaminated water or undercooked seafood. Parenteral transmission (e.g., childbirth, unprotected intercourse, intravenous drug abuse [IVDA], and needle stick) Parenteral transmission (e.g., IVDA, unprotected intercourse); risk from transfusion is almost nonexistent due to screening of the blood supply.


Pathoma_Husain

Pathoma_Husain. Parenteral transmission (e.g., IVDA, unprotected intercourse); risk from transfusion is almost nonexistent due to screening of the blood supply. Dark urine due to t urine urobilinogen (UCB is not water soluble and, thus, is absent from urine) Increased risk for pigmented bilirubin gallstones UCB is fat soluble and can deposit in the basal ganglia (kernicterus) leading to neurological deficits and death. Treatment is phototherapy (makes UCB water soluble). Jaundice during stress (e.g., severe infection); otherwise, not clinically significant Liver is dark; otherwise, not clinically significant Rotor syndrome is similar to Dubin-Johnson syndrome, but lacks liver discoloration. Dark urine (due to bilirubinuria) and pale stool Pruritus due to t plasma bile acids Hypercholesterolemia with xanthomas Steatorrhea with malabsorption of fat-soluble vitamins Dark urine due to t urine bilirubin; urine urobilinogen is normal or decreased.


Pathoma_Husain

Pathoma_Husain. Dark urine due to t urine bilirubin; urine urobilinogen is normal or decreased. Acute hepatitis; no chronic state. Anti-virus IgM marks active infection. Antivirus IgG is protective, and its presence indicates prior infection or immunization (immunization is available for HAV). HEV infection in pregnant women is associated with fulminant hepatitis (liver failure with massive liver necrosis). Results in acute hepatitis; chronic disease occurs in 20% of cases (Table 11.3). Results in acute hepatitis; chronic disease occurs in most cases. HCV-RNA test confirms infection; decreased RNA levels indicate recovery; persistence indicates chronic disease. Dependent on HBV for infection; superinfection upon existing HBV is more severe than coinfection (infection with HBV and HDV at the same time) f}~,. ,f: Fig.11 .7 Chronic hepatitis. Table 11.3: Serologic Markers of Hepatitis B Virus STAGE HBsAG ~!:AG AND HBV HBcAB HBsAB marker to rise) + (presence > 6 +/-; presence of


Pathoma_Husain

Pathoma_Husain. ,f: Fig.11 .7 Chronic hepatitis. Table 11.3: Serologic Markers of Hepatitis B Virus STAGE HBsAG ~!:AG AND HBV HBcAB HBsAB marker to rise) + (presence > 6 +/-; presence of Chronic months defines HBeAg or HBV DNA IgG chronic state) indicates infectivity. II. VIRAL HEPATITIS A. Inflammation ofliver parenchyma, usually due to hepatitis virus (Table 11.2); other causes include EBV and CMV. B. Hepatitis virus causes acute hepatitis, which may progress to chronic hepatitis. C. Acute hepatitis presents as jaundice (mixed CB and UCB) with dark urine (due to CB), fever, malaise, nausea, and elevated liver enzymes (ALT > AST). 1. Inflammation involves lobules of the liver and portal tracts and is characterized by apoptosis of hepatocytes (Fig. 11.6). 2. Some cases may be asymptomatic with elevated liver enzymes. 3. Symptoms last < 6 months. D. Chronic hepatitis is characterized by symptoms that last > 6 months. 1. Inflammation predominantly involves portal tract (Fig. 11.7) 2.


Pathoma_Husain

Pathoma_Husain. 3. Symptoms last < 6 months. D. Chronic hepatitis is characterized by symptoms that last > 6 months. 1. Inflammation predominantly involves portal tract (Fig. 11.7) 2. Risk of progression to cirrhosis III. CIRRHOSIS A. End-stage liver damage characterized by disruption of the normal hepatic parenchyma by bands of fibrosis and regenerative nodules of hepatocytes (Fig. 11.8) B. Fibrosis is mediated by TGF-~ from stellate cells which lie beneath the endothelial cells that line the sinusoids. C. Clinical features 1. Portal hypertension leads to i. Ascites (fluid in the peritoneal cavity) ii. Congestive splenomegaly/hypersplenism iii. Portosystemic shunts (esophageal varices, hemorrhoids, and caput medusae) Fig. 11.8 Cirrhosis. A, Microscopic appearance. B, Gross appearance. (8, Courtesy of humpath.com)


Pathoma_Husain

Pathoma_Husain. Fig. 11.8 Cirrhosis. A, Microscopic appearance. B, Gross appearance. (8, Courtesy of humpath.com) Exocrine Pancreas, Gallbladder, and Liver Pathology iv. Hepatorenal syndrome (rapidly developing renal failure secondary to cirrhosis) 2. Decreased detoxification results in i. Mental status changes, asterixis, and eventual coma (due tot serum ammonia); metabolic, hence reversible ii. Gynecomastia, spider angiomata, and palmar erythema due to hyperestrinism iii. Jaundice 3. Decreased protein synthesis leads to i. Hypoalbuminemia with edema 11. Coagulopathy due to decreased synthesis of clotting factors; degree of deficiency is followed by PT. IV. A. Damage to hepatic parenchyma due to consumption of alcohol 1. Most common cause ofliver disease in the West B. Fatty liver is the accumulation of fat in hepatocytes (Fig. 11.9A). 1. Results in a heavy, greasy liver; resolves with abstinence (Fig. 11.9B)


Pathoma_Husain

Pathoma_Husain. B. Fatty liver is the accumulation of fat in hepatocytes (Fig. 11.9A). 1. Results in a heavy, greasy liver; resolves with abstinence (Fig. 11.9B) C. Alcoholic hepatitis results from chemical injury to hepatocytes; generally seen with binge drinking 1. Acetaldehyde (metabolite of alcohol) mediates damage. 2. Characterized by swelling of hepatocytes with formation of Mallory bodies (damaged cytokeratin filaments, Fig. 11.10), necrosis, and acute inflammation 3. Presents with painful hepatomegaly and elevated liver enzymes (AST > ALT); may result in death D. Cirrhosis is a complication of long-term, chronic alcohol-induced liver damage; occurs in 10-20% of alcoholics V. A. Fatty change, hepatitis, and/or cirrhosis that develop without exposure to alcohol (or other known insult) B. Associated with obesity C. Diagnosis of exclusion; ALT > AST VI. HEMOCHROMATOSIS


Pathoma_Husain

Pathoma_Husain. A. Fatty change, hepatitis, and/or cirrhosis that develop without exposure to alcohol (or other known insult) B. Associated with obesity C. Diagnosis of exclusion; ALT > AST VI. HEMOCHROMATOSIS A. Excess body iron leading to deposition in tissues (hemosiderosis) and organ damage (hemochromatosis) 1. Tissue damage is mediated by generation of free radicals. B. Due to autosomal recessive defect in iron absorption (primary) or chronic transfusions (secondary) Fig.11.9 Fatty liver. A, Microscopic appearance. B, Gross appearance. (B, Courtesy of Jerome Taxy, Fig. 11.10 Mallory bodies, alcoholic hepatitis. MD) 1. Primary hemochromatosis is due to mutations in the HFE gene, usually C282Y (cysteine is replaced by tyrosine at amino acid 282). C. Presents in late adulthood 1. Classic triad is cirrhosis, secondary diabetes mellitus, and bronze skin; other findings include dilated cardiomyopathy, cardiac arrhythmias and gonadal dysfunction (due to testicular atrophy). 2.


Pathoma_Husain

Pathoma_Husain. Classic triad is cirrhosis, secondary diabetes mellitus, and bronze skin; other findings include dilated cardiomyopathy, cardiac arrhythmias and gonadal dysfunction (due to testicular atrophy). 2. Labs show t ferritin, -1, TIBC, t serum iron, and t % saturation. 3. Liver biopsy reveals accumulation of brown pigment in hepatocytes (Fig. 11.llA); Prussian blue stain distinguishes iron (blue) from lipofuscin (Fig. 11.llB). i. Lipofuscin is a brown pigment that is a by-product from the turnover ('wear and tear') of peroxidized lipids; it is commonly present in hepatocytes (Fig. 11.llC). D. Increased risk ofhepatocellular carcinoma E. Treatment is phlebotomy. VII. WILSON DISEASE A. Autosomal recessive defect (ATP7B gene) in ATP-mediated hepatocyte copper transport 1. Results in lack of copper transport into bile and lack of copper incorporation into ceruloplasmin B. Copper builds up in hepatocytes, leaks into serum, and deposits in tissues.


Pathoma_Husain

Pathoma_Husain. B. Copper builds up in hepatocytes, leaks into serum, and deposits in tissues. 1. Copper-mediated production of hydroxyl free radicals leads to tissue damage. C. Presents in childhood with 1. 2. Neurologic manifestations (behavioral changes, dementia, chorea, and Parkinsonian symptoms due to deposition of copper in basal ganglia) 3. Kayser-Fleisher rings in the cornea D. Labs show t urinary copper, -1, serum ceruloplasmin, and t copper on liver biopsy. E. Increased risk of hepatocellular carcinoma F. Treatment is D-penicillamine (chelates copper). VIII. PRIMARY BILIARY CIRRHOSIS A. Autoimmune granulomatous destruction of intrahepatic bile ducts 1. Classically arises in women (average age is 40 years) 2. Associated with other autoimmune diseases B. Etiology is unknown; antimitochondrial antibody is present. C. Presents with features of obstructive jaundice D. Cirrhosis is a late complication. IX. PRIMARY SCLEROSING CHOLANGITIS


Pathoma_Husain

Pathoma_Husain. B. Etiology is unknown; antimitochondrial antibody is present. C. Presents with features of obstructive jaundice D. Cirrhosis is a late complication. IX. PRIMARY SCLEROSING CHOLANGITIS A. Inflammation and fibrosis of intrahepatic and extrahepatic bile ducts Fig. 11.11 Hemochromatosis. A, Iron deposition in hepatocytes. B, Prussian blue stain. C, Lipofuscin in hepatocytes for comparison. Exocrine Pancreas, Gallbladder, and Liver Pathology 1. Periductal fibrosis with an 'onion-skin' appearance (Fig. 11.12) 2. Uninvolved regions are dilated resulting in a "beaded" appearance on contrast imaging. B. Etiology is unknown, but associated with ulcerative colitis; p-ANCA is often positive. C. Presents with obstructive jaundice; cirrhosis is a late complication. D. Increased risk for cholangiocarcinoma X. REYE SYNDROME A. Fulminant liver failure and encephalopathy in children with viral illness who take aspirin 1. Likely related to mitochondrial damage ofhepatocytes


Pathoma_Husain

Pathoma_Husain. X. REYE SYNDROME A. Fulminant liver failure and encephalopathy in children with viral illness who take aspirin 1. Likely related to mitochondrial damage ofhepatocytes B. Presents with hypoglycemia, elevated liver enzymes, and nausea with vomiting; may progress to coma and death XI. HEPATIC ADENOMA A. Benign tumor ofhepatocytes B. Associated with oral contraceptive use; regresses upon cessation of drug C. Risk of rupture and intraperitoneal bleeding, especially during pregnancy 1. Tumors are subcapsular and grow with exposure to estrogen. XII. HEPATOCELLULAR CARCINOMA A. Malignant tumor of hepatocytes B. Risk factors include 1. Chronic hepatitis (e.g., HBV and HCV) 2. Cirrhosis (e.g., alcohol, nonalcoholic fatty liver disease, hemochromatosis, Wilson disease, and AlAT deficiency) 3. C. Increased risk for Budd-Chiari syndrome 1. Liver infarction secondary to hepatic vein obstruction 2. Presents with painful hepatomegaly and ascites


Pathoma_Husain

Pathoma_Husain. C. Increased risk for Budd-Chiari syndrome 1. Liver infarction secondary to hepatic vein obstruction 2. Presents with painful hepatomegaly and ascites D. Tumors are often detected late because symptoms are masked by cirrhosis; poor prognosis E. Serum tumor marker is alpha-fetoprotein. XIII. METASTASIS TO LIVER A. More common than primary liver tumors; most common sources include colon, pancreas, lung, and breast carcinomas. B. Results in multiple nodules in the liver (Fig. 11.13) C. Clinically may be detected as hepatomegaly with a nodular free edge of the liver Fig.11 .12 'Onion-skin' fibrosis, primary sclerosing Fig. 11.13 Metastatic carcinoma involving liver. cholangitis. (Courtesy of Jerome Taxy, MD) I. HORSESHOE KIDNEY A. Conjoined kidneys usually connected at the lower pole (Fig. 12.1); most common congenital renal anomaly


Pathoma_Husain

Pathoma_Husain. I. HORSESHOE KIDNEY A. Conjoined kidneys usually connected at the lower pole (Fig. 12.1); most common congenital renal anomaly B. Kidney is abnormally located in the lower abdomen; horseshoe kidney gets caught on the inferior mesenteric artery root during its ascent from the pelvis to the abdomen. II. RENAL AGENESIS A. Absent kidney formation; may be unilateral or bilateral B. Unilateral agenesis leads to hypertrophy of the existing kidney; hyperfiltration increases risk of renal failure later in life. C. Bilateral agenesis leads to oligohydramnios with lung hypoplasia, flat face with low set ears, and developmental defects of the extremities (Potter sequence, Fig. 12.2); incompatible with life III. DYSPLASTIC KIDNEY A. Noninherited, congenital malformation of the renal parenchyma characterized by cysts and abnormal tissue (e.g., cartilage, Fig. 12.3) B. Usually unilateral; when bilateral, must be distinguished from inherited polycystic kidney disease IV.


Pathoma_Husain

Pathoma_Husain. B. Usually unilateral; when bilateral, must be distinguished from inherited polycystic kidney disease IV. A. Inherited defect leading to bilateral enlarged kidneys with cysts in the renal cortex and medulla (Fig. 12.4) B. Autosomal recessive form presents in infants as worsening renal failure and hypertension; newborns may present with Potter sequence. 1. Associated with congenital hepatic fibrosis (leads to portal hypertension) and hepatic cysts C. Autosomal dominant form presents in young adults as hypertension (due to increased renin), hematuria, and worsening renal failure. 1. Due to mutation in the APKDl or APKD2 gene; cysts develop over time. 2. Associated with berry aneurysm, hepatic cysts, and mitral valve prolapse V. A. Inherited (autosomal dominant) defect leading to cysts in the medullary collecting ducts B. Parenchymal fibrosis results in shrunken kidneys and worsening renal failure. I. BASIC PRINCIPLES


Pathoma_Husain

Pathoma_Husain. V. A. Inherited (autosomal dominant) defect leading to cysts in the medullary collecting ducts B. Parenchymal fibrosis results in shrunken kidneys and worsening renal failure. I. BASIC PRINCIPLES A. Acute, severe decrease in renal function (develops within days) B. Hallmark is azotemia (increased BUN and creatinine [Cr]), often with oliguria. pathoma.com C. Divided into prerenal, postrenal, and intrarenal azotemia based on etiology II. PRERENAL AZOTEMIA A. Due to decreased blood flow to kidneys (e.g., cardiac failure); common cause of ARF B. Decreased blood flow results in ,I, GFR, azotemia, and oliguria. C. Reabsorption of fluid and BUN ensues (serum BUN:Cr ratio > 15); tubular function remains intact (fractional excretion of sodium [FENa] < 1% and urine osmolality [osm] > 500 mOsm/kg). III. POSTRENAL AZOTEMIA A. Due to obstruction of urinary tract downstream from the kidney (e.g., ureters) B. Decreased outflow results in ,I, GFR, azotemia, and oliguria.


Pathoma_Husain

Pathoma_Husain. III. POSTRENAL AZOTEMIA A. Due to obstruction of urinary tract downstream from the kidney (e.g., ureters) B. Decreased outflow results in ,I, GFR, azotemia, and oliguria. C. During early stage of obstruction, increased tubular pressure "forces" BUN into the blood (serum BUN:Cr ratio > 15); tubular function remains intact (FENa < 1% and urine osm > 500 mOsm/kg). D. With long-standing obstruction, tubular damage ensues, resulting in decreased reabsorption of BUN (serum BUN:Cr ratio < 15), decreased reabsorption of sodium (FEN a > 2%), and inability to concentrate urine (urine osm < 500 mOsm/kg). IV. ACUTE TUBULAR NECROSIS A. Injury and necrosis of tubular epithelial cells (Fig. 12.5); most common cause of acute renal failure (intrarenal azotemia) B. Necrotic cells plug tubules; obstruction decreases GFR. 1. Brown, granular casts are seen in the urine.


Pathoma_Husain

Pathoma_Husain. B. Necrotic cells plug tubules; obstruction decreases GFR. 1. Brown, granular casts are seen in the urine. C. Dysfunctional tubular epithelium results in decreased reabsorption of BUN (serum BUN:Cr ratio < 15), decreased reabsorption of sodium (FEN a > 2%), and inability to concentrate urine (urine osm < 500 mOsm/kg). D. Etiology may be ischemic or nephrotoxic. 1. Ischemia-Decreased blood supply results in necrosis of tubules. i. Often preceded by prerenal azotemia ii. Proximal tubule and medullary segment of the thick ascending limb are particularly susceptible to ischemic damage. 2. Nephrotoxic-Toxic agents result in necrosis of tubules. i. Proximal tubule is particularly susceptible. ii. Causes include aminoglycosides (most common), heavy metals (e.g., lead), myoglobinuria (e.g., from crush injury to muscle), ethylene glycol (associated with oxalate crystals in urine), radiocontrast dye, and urate (e.g., tumor lysis syndrome).


Pathoma_Husain

Pathoma_Husain. iii. Hydration and allopurinol are used prior to initiation of chemotherapy to decrease risk of urate-induced ATN. :,j.U,,J .• /J',.// t~.. \ f , ',· ~-.,;i· ~4' , ♦ i". ~·t,)l ', : .. ti'•;',,1 . •..' !~,-~i >,,:' : ~··~t:, .·· / .:. :-~ l6 ,. .....,-.-·.\· ,:j~I 1 , ;' 1,'' I ~~ • ,f'•~,.~,,,1' •• ' ~••• I, Fig. 12.1 Horseshoe kidney. (Courtesy of Fig. 12.2 Potter sequence, (Courtesy of humpath, Fig. 12.3 Dysplastic kidney, (Courtesy of Aliya humpath,com) com) Husain, MD) E. Clinical features 1. Oliguria with brown, granular casts 2. 3. Hyperkalemia (due to decreased renal excretion) with metabolic acidosis F. Reversible, but often requires supportive dialysis since electrolyte imbalances can be fatal 1. Oliguria can persist for 2-3 weeks before recovery; tubular cells (stable cells) take time to reenter the cell cycle and regenerate. V. ACUTE INTERSTITIAL NEPHRITIS


Pathoma_Husain

Pathoma_Husain. V. ACUTE INTERSTITIAL NEPHRITIS A. Drug-induced hypersensitivity involving the interstitium and tubules (Fig. 12.6); results in acute renal failure (intra renal azotemia) B. Causes include NSAIDs, penicillin, and diuretics. C. Presents as oliguria, fever, and rash days to weeks after starting a drug; eosinophils may be seen in urine. D. Resolves with cessation of drug E. May progress to renal papillary necrosis VI. RENAL PAPILLARY NECROSIS A. Necrosis of renal papillae B. Presents with gross hematuria and flank pain C. Causes include 1. Chronic analgesic abuse (e.g., long-term phenacetin or aspirin use) 2. 3. 4. I. BASIC PRINCIPLES A. Glomerular disorders characterized by proteinuria (> 3.5 g/day) resulting in 1. 2. Hypogammaglobulinemia-increased risk of infection 3. Hypercoagulable state-due to loss of antithrombin III 4. II. MINIMAL CHANGE DISEASE (MCD) A. Most common cause of nephrotic syndrome in children


Pathoma_Husain

Pathoma_Husain. Hypercoagulable state-due to loss of antithrombin III 4. II. MINIMAL CHANGE DISEASE (MCD) A. Most common cause of nephrotic syndrome in children B. Usually idiopathic; may be associated with Hodgkin lymphoma Fig. 12.4 Polycystlc kidney disease. (Courtesy of Fig. 12.5 Acute tubular necrosis. Fig. 12.6 Acute interstitial nephritis. Jamie Steinmet z, MD) C. Normal glomeruli on H&E stain (Fig. 12.7A); lipid may be seen in proximal tubule cells. D. Effacement of foot processes on electron microscopy (EM, Fig. 12.7B) E. No immune complex deposits; negative immunofluorescence (IF) F. Selective proteinuria (loss of albumin, but not immunoglobulin) G. Excellent response to steroids (damage is mediated by cytokines from T cells) III. FOCAL SEGMENTAL GLOMERULOSCLEROSIS (FSGS) A. Most common cause of nephrotic syndrome in Hispanics and African Americans B. Usually idiopathic; may be associated with HIV, heroin use, and sickle cell disease