Pulmonary How do you calculate the Aa gradient?

What causes an A-a gradient and how is it useful in differentiating causes of hypoxemia? What are some causes of ventilation defects? What are some causes of perfusion defects? What are some causes of diffusion defects? What are some causes of shunting? What are some causes of hypoxemia with a normal Aa gradient? Define Functional Residual Capacity, FRC (Refer to Pulmonary attachment 1). Define Total Lung Capacity, TLC Difference in partial pressure of Oxygen, PO2, between the alveolar PO2 and arterial PO2 PAO2=FiO2(713) - arterial PCO2/0.8 A-a gradient is caused by a mismatch between ventilation and perfusion. Hypoxemia of pulmonary origin causes an increased Aa gradient (>30). Hypoxemia of extrapulmonary origin has a normal A-a gradient. Impaired O2 delivery to the alveoli for gas exchange, e.g. from airway collapse due to respiratory distress syndrome or atelectasis. Decreased or absent blood flow to the alveoli, e.g. pulmonary embolus O2 cannot diffuse across alveolar-capillary interface, e.g. pulmonary fibrosis or pulmonary edema. Causes decreased DLCO A shunt is technically blood going from right to left because of heart issues, e.g. right to left shunting from tetralogy of fallot. Depression of the respiratory center in the medulla (barbiturates, brain injury); upper airway obstruction (epiglottitis, croup); Chest bellows dysfunction (paralyzed diaphragm, ALS with degeneration of anterior horn cells).

Total amount of air in the lungs at the end of normal expiration Total amount of air in a fully expanded lung

Define Residual Volume, RV Define Tidal Volume, TV Define Forced Vital Capacity, FVC Define Forced Expiratory Volume, 1 second, FEV1 What is the normal FEV1/FVC? Define Expiratory Reserve Volume, ERV

Volume of air left over in the lung after maximal expiration: FRCERV Volume of air that enters/exits the lungs during normal respiration Total amount of air expelled after maximal inspiration Amount of air expelled from the lungs in 1 second after maximal inspiration 70-80% Amount of air forcibly expelled at the end of normal expiration TLC decreased, RV decreased, FEV1 decreased, FVC decreased, FEV1/FVC normal to increased, PaO2 decreased, A-a gradient increased (if disease of lungs, not just restriction of chest wall TLC increased, RV increased, FEV1 decreased, FVC decreased, FEV1/FVC decreased, PaO2 decreased, A-a gradient increased Difficulty breathing. Can be due to stimulation of J receptors causing decrease in full inspiration. Also decreased compliance, e.g. interstitial fibrosis; increased airway resistance, e.g. chronic bronchiti; chest bellows disease, e.g. obesity; kyphoscoliosis, interstitial inflammation or fluid accumulation, e.g. left sided heart failure. They're at the bifurcation of airways, larynx and distal esophagus

Describe spirometry in restrictive lung disease Describe spirometry in obstructive lung disease

Define Dyspnea and list some causes. Where are cough receptors located?

What is the most common cause of cough with a normal CXR? What causes nocturnal cough? What causes productive cough?

What drugs cause cough? Define hemoptysis and the mechanisms. What are some causes of hemoptysis?

Postnasal discharge GERD from acid refluxing into the bronchial tree at night. Bronchial asthma due to airway constriction Chronic bronchitis, usually associated with smoking cigarettes. Typical bacterial pneumonia. Bronchiectasis ACE inhibitors-inhibit degradation of bradykinin which causes mucosal swelling and irritation in the tracheobronchial tree. Aspirin causes increases in Leukotriene C, D and E4 which are all bronchoconstrictors Coughing up blood-tinged sputum. Caused by parenchymal necrosis and/or bronchial/pulmonary vessel damage. Chronic bronchitis (most common), pneumonia, bronchogenic carcinoma, tuberculosis, bronchiectasis, aspergilloma (fungus in a cavitary lesion) Rapid, shallow breathing, more than 20 breaths/minute. Causes are restrictive lung disease, pleuritic chest pain, pulmonary embolus with infarction (tachypnea is the key finding) shift of trachea from large changes in pleural fluid volume. Causes are pressure in contralateral lung, large tension pneumothorax, large pleural effusion; decreased volume in ipsalateral lung, large spontaneous pneumothorax, resorption atelectasis. Palpable thrill (vibration) transmitted through the chest when the patient says "99," or "E" Emphysema or asthma with increased AP diameter from increased total lung capacity.

Define tachypnea and list the causes.

Define tracheal shift and list the mechanism. What is vocal tactile fremitus? What causes decreased tactile fremitus?

What causes increased tactile fremitus? What causes absent tactile fremitus? What causes dull and hyperresonant percussion? What is the origin and mechanism of normal breath sounds? Where does laminar air flow start?

Sound travels better through fluid/solid so any type of lung consolidation, pneumonia, etc. Atelectasis/collapse of airways, fluid/effusion, air in pleural space (pneumothorax) Dull percussion comes from pleural effusions, lung consolidations, atelectasis. Hyperresonant percussion comes from pneumothorax, asthma or emphysema Normal breath sounds come from the trachea and are caused by air velocity and turbulence inducing vibrations in airway walls Terminal bronchioles where the increased surface area converts turbulent to laminar flow Sound like air blowing through a tube-this is normal over the trachea but is always abnormal over the bronchi. Causes a loud, high pitched sound with a tubular or hollow quality. Expiration is longer than inspiration. Means that there is consolidation or patent but partially collapsed bronchi Tracheal sounds that are modified in the alveoli. Inspiratory to expiratory ratio is 3:1. Diminished in emphysema and asthma due to increased AP diameter. Absent in pneumothorax, atelectasis or effusion Normal breath sounds over the main bronchi with an equal inspiratory and expiratory ratio.

What are tubular breath sounds?

What are vesicular breath sounds? What are bronchovesicular breath sounds?

What are crackles and how are they caused?

Extra sounds, usually inspiratory, that sound like (you guessed it), crackles! Early and midinspiratory crackles are due to secretions in proximal large to medium sized airways. These clear with coughing. Late inspiratory crackles are due to reopening of distal airways partially occluded by increased interstitial pressure (fluid, transudate, pus). These do not clear with coughing and vary from fine to course High pitched musical sound usually in expiration. Caused by inflammation of segmental bronchi and small airways by asthma or chronic bronchitis; pulmonary edema constricting airway (cardiac asthma); pulmonary infarction (release of TXA from platelets in the embolus causes bronchoconstriction Low pitched snoring sounds during inspiration or expiration. Due to secretions in large airways (bronchus or trachea). Usually clear with coughing, common in chronic bronchitis High pitched inspiratory sound. Indicates upper airway obstruction. Caused by epiglottitis (H. Influenzae), croup (parainfluenza) Two inflamed surfaces (pleural and parietal) rubbing against each other. Usually happens at the end of inspiration and beginning of expirations when things are changing direction. Caused by pleuritis due to cancer, infarction, pneumonia, serositis (SLE). Disappears with alrge effusion bc separates layers and stays with holding breath. Newborns should not grunt after 24 hours. It's a sign of respiratory distress syndrome.

What is wheezing and how is it caused? What are Rhonchi and how are they caused? What is inspiratory stridor and how is it caused?

What is a pleural friction rub and how is it caused? What does grunting in a newborn mean?

What is bronchophony and egophony? What is a flow volume loop? Where is maximal inspiration on the diagram? (see Pulmonary attachment 2 for following)

Caused by alveolar consolidations. Spoken numbers, syllables are heard more distinctly through stethoscope. Egophany is when the patient says E and you hear an A through the stethoscope. Plot of inspiratory and expiratory flow rate(L/sec) versus lung volume(L)

Begins at point A, RV and goes to point B, TLC Begins at point B, TLC, and goes to point C, PEF. Occurs early in expiratory phase of loop due to elastic recoil of the lungs with low resistance and large caliber. Slope decreases to point A as resistance increases and airways get smaller. Vital Capacity TLC is increased and RV is increased. AKA left shifted curve. Decreased PEF. Can have concavity at C from mucus plugs or collapsed airways.

Define Peak Expiratory Flow (PEF) What is the volume between points B and C? Describe the flow-volume loop in obstructive lung disease. Describe the flow-volume loop in restrictive lung disease.

What is Choanal Atresia?

TLC is decreased, RV is decreased. AKA right shifted curve. Unilateral or bilateral bony septum between the nose and pharynx. Newborn urns cyanotic on breast feeding but crying causes them to pink up again

What is a Nasal Polyp? Define Obstructive Sleep Apnea

Non-neoplastic tumefactions which develop as a response to chronic inflammation. Allergic polyps are the most common and are most often seen in asults with IgE mediated allergies. Also associated with aspirin and other NSAIDs b/c Cyclooxegenase block increases Leukotrienes whcih results in bronchoconstriction. Oten associated with CF Excessive snoring with intervals of breath cessation (apnea) Most commonly a result of obesity causing the pharyngeal muscles to collapse under the weight of the tissue. Can also result from tonsilar hypertrophy or nasal septum deviation. Airway obstruction causes CO2 retention resulting in hypoxemia. Decreased PO2 and O2 saturation during apnea with increase in PCO2. See excessive snoring with apneic periods and excessive daytime somnolence. Can cause pulmonary arterial hypertension leading to Right Ventricular Hypertrophy and polycythemia secondary to hypoxemia. Inflammation of the sinuses, most often maxillary or ethmoid sinuses. Caused by URI blocking drainage of sinuses into nasal cavity. Can be caused by a deviated nasal septum, allergic rhinitis, barotrauma, or cigarettes. Pathogens implicated are rhinovirus, strep pneumoniae, anaerobes (chronic sinusitis), systemic fungi (diabetics due to Mucor species).

What causes obstructive sleep apnea?

What is the pathogenesis and clinical findings in sleep apnea?

Define Sinusitis and describe its causes.

What is a Nasopharyngeal Carcinoma?

Most common malignant tumor of the nasopharynx, more common in males and increased incidence in the Chinese and African populations. Closely related to EBV. Often causes squamous cell carcinoma or undifferentiated cancers which can metastasize to cervical lymph nodes. Carcinoma most commonly located on the true vocal cords. Mostly keratinizing squamous cell carcinomas, mostly in med. Related to cigarette smoking, alcohol (synergistic with cigarettes), HPV 6 and 11 and squamous papillomas and papillomatosis. Persistent hoarseness from cervical lymphadenopathy is common. Loss of lung volume due to inadequate expansion of the airspaces (collapse). Collapse happens because of lack of air and distal resorption of air through pores of Kohn in the alveolar walls. May see ipsilateral elevation of the diaphragm and tracheal deviation. Treat with incentive spirometry, CPAP or PEEP. Airway obstruction in bronchiols, segmental bronchi or bronchi, by thick secretions which prevents air from reaching the alveoli. Can be caused by mucus or mucopruluent plug after surgery, aspiration of foreign material or centrally located bronchogenic carcinoma. Air or fluid in the pleural cavity under increased pressure collapses small airways beneath the pleura.

Define Laryngeal Carcinoma.

What is Atelectasis?

What is resorption atelectasis? What is compression atelectasis?

What is atelectasis due to loss of surfactant?

What is Respiratory Distress Syndrome?

What are complications of respiratory distress syndrome?

What is Pulmonary Edema and what are the causes?

Synthesized by Type II pneumocytes starting in the 28th week of gestation. Stored in lamellar bodies. Major component is phosphatidylcholine (lecithin). Synthesis is increased by cortisol and thyroxine but decreased by insulin. Surfactant reduces surface tension so airways don't collapse. Without surfactant, airways can collapse causing atelectasis. Decreased surfactant in lungs results in atelectasis and respiratory distress from massive intrapulmonary shunting. Collapsed alveoli are lined by hyaline membranes (from protein leaking out of damaged alveoli). Causes respiratory difficulty, grunting, tachypnea, intercostal retractions and hypoxemia with respiratory acidosis. Superoxide radicals from O2 therapy can cause blindness (retinopathy of prematurity) and damage to small airways (bronchopulonary dysplasia). Can cause intraventricular hemorrhage, patent ductus arteriosus from hypoxemia, necrotizing enterocolitis from intestinal ischemia (allows entry of gut bacteria into intestinal walls) and hypoglycemia leading to seizures and neuronal damage. Collection of fluid. Can be due to Starling forces from left sided heart failure, volume overload or mitral stenosis. This produces transudate. Can be exudate from microvascular or alveolar injury resulting from infection. Can be from aspiration, drugs, high altitude or ARDS.

What is Acute Respiratory Distress Syndrome, ARDS?

Noncardiogenic pulmonary edema from acute alveolar-capillary damage. Caused by direct injury to the lungs or systemic disease. Risk factors are gram (-) sepsis, gastric aspiration, severe trauma and shock, diffuse pulmonary infections (SARS, hantavirus), Heroin, smoke inhalation, acute pancreatitis, cardiopulmonary bypass, DIC, amniotic fluid or fat embolism. Acute damage to alveolar capillary walls and epithelial cells results in alveolar macrophages releasing cytokines. Capillary damage and chemotactic factors allow neutrophils and exudate to leak producing hyaline membranes. Neutrophils damage Type I and II pneumocytes, reducing surfactant and causing atelectasis. Dyspnea/tachypnea, late inspiratory crackles, severe hypoxemia not responsive to 100% O2, increased pulmonary wedge pressure, increased A-a gradient, bilateral infiltrates and consolidations. Community acquired which can be typical or atypical and hospital acquired, aka nosocomial. Most caused by bacterial pathogens, particularly Strep Pneumoniae. Pathogenesis is via inhalation of aerosol from infected person or aspiratin of nasopharyngeal flora while sleeping. Begins as acute bronchitis and spreads locally into the lungs, usually lower lobes or right middle lobes. Causes patchy consolidations and may have microabscesses.

What is the pathogenesis of ARDS?

What are clinical signs/symptoms of ARDS? What are the subtypes of Pneumonia?

Describe the pathogenesis of typical pneumonia. Describe the pathogenesis of bronchopneumonia.

Describe clinical findings in lobar pneumonia.

Complete or almost complete consolidation of a lobe of the lung. Can be complicated by lung abscesses, empyema or sepsis. See sudden onset of fever with productive cough, chest pain, tachycardia, dullness to percussion, increased tactile fremitus, late inspiratory crackles, bronchial breath sounds, bronchophany and egophany. Usually caused by mycoplasma pneumoniae, also chlamydophilia pneumoniae, RSV, influenzavirus, and adenovirus. Contracted by inhalation of droplets. Causes patchy, mononuclear infiltrate but the alveolar spaces are usually free of exudate. Insidious onset with nonproductive cough, low grade fever, chest pain, flu like symptoms including pharyngitis, laryngitis, myalgia and headache. No consolidation. Happens in patients with severe underlying disease, immunosuppresion, or who are on antibiotic therapy. Respirators are the most common source of infection. Usually gram (-) bacteria, often pseudomonas, E coli, or gram (+) like staph aureus. In immunocompromised, can be opportunistics like CMV, Pneumocystis Jirovecis, Aspergillus-fumigatus. From inhalation of Mycobacterium Tuberculosis. Infects phagosomes of alveolar macrophages and produces a protein that prevents fusion of the lysosome with the phagosome. Strict aerobe, acid fast. Cord factor is major virulence factor. Drug resistance by mutations in mycolic acid or catalase peroxidase (activates Isoniazid).

Describe clinical findings in atypical pneumonia.

Describe clinical findings in nosocomial pneumonia.

Describe pneumonia from Tuberculosis.

Describe Primary TB Infection.

Subpleural location, usually upper part of lower lobes or lower part of upper lobes. Causes Ghon focus (caseous necrosis) in periphery and Ghon complex in hilar lymph nodes. Produces a calcified granuloma or area of scar tissue Due to reactivation of primary TB. Usually involves apices in upper lobes b/c increased V/Q ratio. Causes cavitary lesions from release of cytokines by T Cells. Causes fever, drenching night sweats, weight loss. May cause miliary TB with invasion into bronchus, lymphatics or extrapulmonary sites like the kidney. Spread to vertebra is called Pott's disease. Atypical mycobacterium causing atypical pneumonia in AIDS patients. Happens when CD4+ T Cell count falls below 50 cells/mm3. Often disseminates and co-occurs with systemic fungal infection. Rhinovirus, transmitted by hand to nose/eye contact. Less common are coronavirus, adenovirus, influenza C and coxsackievirus Acute chest syndrome: fever with pleuritis

Describe Secondary TB Infection. Describe pneumonia from Mycobacterium Avium Intracellulare What is the most common cause of the common cold? What does Coxsackievirus cause? What is the most common viral cause of atypical pneumonia and bronchiolitis in children and otitis media in older children?

Respiratory Syncitial Virus. Occurs in late fall and winter. Can give Palivizumab to high risk kids (passive immunity)

What is the most common viral cause of laryngotracheobronchitis (croup) in infants?

Parainfluenza. Causes inspiratory stridor from sunmucosal edema obstructing the upper airway. Anterior CXR shows steeple sign in anterior neck.

What is the most common viral cause of pneumonia in immunocompromised hosts? What can happen with aspirin ingestion when a child has influenza? What are signs and symptoms of Rubeola infection? What are signs and symptoms of SARS What is Hantavirus pulmonary syndrome? What is the second most common (bacterial) cause of atypical pneumonia? What is a common bacterial cause of newborn pneumonia? What is the most common baterial cause of atypical pneumonia?

Cytomegalovirus. Enlarged alveolar macrophages/pneumocytes with basophilic inclusions surrounded by a halo. Reye's Syndrome. Causes fatty liver, severe encephalopathy, palmar rash, comiting, lethargy and stupor. Measles. Fever, cough, conjunctivitis and excessive nasal mucous. Koplik spots in the mouth precede rash. Warthin-Finkeldey multinucleated giant cells are characteristic Infects lower respiratory tract and then spreads systemically thus severe respiratory infection and systemic symptoms. Transmission is via inhalation of urine/feces from deer mice in SW US. Causes ARDS, hemorrhage and renal failure. Chlamydophilia pneumoniae. Has a seroepidemiologic association with coronary artery disease. Treat with doxycycline. Chlamydia trachomatis from passage through infected birth canal. Afrebile with staccato cough, conjunctivitis and wheezing. Treat with erythromycin. Mycoplasma Pneumoniae. Insidious onset with low grade fever. Can cause bullous myringitis(inflamed Tympanic membrane), cold autoimmune hemolytic anemia from anti-IgM antibodies.

Describe the signs and symptoms of Coxiella Burnetti infection What is the most common cause of community acquired lobar pneumonia?

Atypical pneumonia, myocarditis, granulomatous hepatitis. Associated with dairy farmers and vetrinarians.

What are signs/symptoms of pneumonia from Staph Aureus? Describe signs and symptoms of infection with Corynebacterium Diptheriae. What are signs and symptoms of infection with Bacillus Anthracis? What are signs and symptoms of Actinomyces infection? What are signs and symptoms of Nocardia infection?

Strep pneumoniae. Rapid onset, productive cough and signs of lobar consolidation. Can test with urine screen. Commonly superimposed on measles or influenza pneumonia or in CF or IV drug users. Hemorrhagic pulmonary edema, yellow sputum, abscess formation and tension pneumatocysts (intrapleural blebs) which can rupture and produce tension pneumothorax. Causes toxin-induced pseudomembranous inflammation producing a shaggy gray membrane in the oropharynx and trachea. Can cause toxic myocarditis from impaired B oxidation of fatty acids in the heart. Cutaneous anthrax initially looks like a scab but swells to form a black scab (eschar) with an area of central necrosis. Pulmonary anthrax causes necrotizing pneumonia, meningitis, splenomegaly and systemic dissemination. Normal flora in tonsils and adenoids. Can produce draining sinuses in the jaw, chest cavity and abdomen. Pus contains yellow specks (sulfur granules) which contain the bacteria. Granulomatous microabscesses in the lungs. Often disseminates to CNS and kidneys.

What are signs and symptoms of infection with Bordatella Pertussis? What are signs and symptoms of infection with H. Influenzae? What are signs and symptoms of Moraxella Catarrhalis infection? What are signs and symptoms of infection with Pseudomonas Aeruginosa? What are signs and symptoms of Klebsiella Pneumoniae infection?

Produces whooping cough-inspiratory whoop between coughing fits. Catarrhal phase is 1-2 weeks and involves mild coughing, rhinorrhea and conjunctivitis. Paroxysmal phase lasts 2-5 weeks and involves coughing in succession followed by inspiratory whoop and absolute lymphocytosis (20,000-50,000). Convalescent pahse lasts 1-2 weeks or more and involves a slow decline in lymphocytosis and coughing. Can cause hemorrhage into skin, conjunctiva, bronchus, brain or rectal prolapse from coughing. Also otitis media and meningoencephalitis. Common cause of sinusitis, otitis media, conjunctivitis, epiglottitis with inspiratory stridor. Swelling of epiglottis produces a thumbprint sign on lateral xray of the neck. Can cause COPD exacerbation. Causes typical pneumonia, especially in the elderly. Causes acute COPD exacerbation, chronic bronchitis, sinusitis and otitis media. Green sputum (pyocyanin), nosocomial pneumonia and pneumonia in CF patients. Often associated with infarction from vessel invasion. Most common gram negative that causes lobar pneumonia and typical pneumonia in nursing home patients and alcoholics. Associated with blood tinged, thick, mucoid sputum, lobar consolidations and abscesses.

What are signs and symptoms of infection with Legionella Pneumophila?

Pneumonia associated with high fever, dry cough, flu like symptoms. May produce tubulointerstitial disease with destruction of the JG apparatus leading to hyporeninemic hypoaldosteronism (type IV renal tubular acidosis-hyponatremia, hyperkalemia, metabolic acidosis). Urine antigen is an excellent screen. The plague!!! Macrophages cannot kill bacteria due to protection by V and W antigens so you get really sick. Bubonic causes infected lymph node which enlarge and mat together and drain to the surface (buboes). Pneumonic and septicemic are just what they sound like. Treat with gentamicin and doxycycline (pneumonic) or gentamicin and streptomycin (bubonic)

What are signs and symptoms of infection with Yersinia Pestis? What are signs and symptoms of infection with Cryptococcus Neoformans?

Granulomatous inflammation with caseation. Acquired from pigeon feces. Aspergilloma-fungus ball that develops in a prior cavitary lesion and cause massive hemoptysis. Allergic bronchopulmonary aspergillosis-type I and III hypersensitivity. IgE increase, eosinophilia, intense inflammation of airways and mucous plugs in terminal bronchioles resulting in bronchiectasis and interstitial lung disease. Vessel invasion with hemorrhagic infarctions and necrotizing bronchopneumonia. Happens to diabetic and immunosuppressed patients. Vessel invasion producing hemorrhagic infarcts in the lungs. Invades the frontal lobes when there is diabetic ketoacidosis (rhinocerebral mucormycosis).

What are signs and symptoms of infection with Aspergillus Fumigatus? What are signs and symptoms of infection with Mucor species?

What are signs and symptoms of infection with Coccidoides Immitis?

What are signs and symptoms of infection with Histoplasma Capsulatum? What are signs and symptoms of infection with Blastomyces Dermatitidis?

Contracted by inhaling arthrospores in dust in arid areas (increased after earthquakes). Causes flu-like symptoms and erythema nodosum and granulomatous inflammation of the lungs with caseous necrosis. Most common systemic fungal infection, endemic in Ohio and Mississippi river valleys. Causes granulomatous inflammation with caseous necrosis, simulating TB. Produces coin lesions, consolidations, milary spread and cavitation. Causes marked dystrophic calcification of granulomas and multiple calcifications in the spleen. Male dominant disease, common in Great lakes, central and southern US. Causes skin disease that simulates squamous cell carcinoma and lung disease with granulomatous inflammation and caseous necrosis. Cysts and trophozoites attach to Type I pneumocytes. Most common AIDS-defining infection, CD4+ count <200. Fever, dyspnea and severe hypoxemia, diffuse intra-alveolar foamy exudates with cup chaped cysts (under silver or Giemsa stain). Diffuse alveolar and interstitial infiltrates. Aspiration of oropharyngeal material. Risk factors are alcoholism, loss of consciousness and recent dental work. Can also be a complication of pneumonia, a result of septic embolism or from an obstructive lung neoplasia. Aerobic and anaerobic streptococci, staph species, prevotella, fusobacterium

What are signs and symptoms of infection with Pneumocystis Jiroveci?

What are the common causes of lung abscesses? What are the most common pathogens in lung abscesses?

Where are most lung abscesses due to aspiration located? What are clinical findings in a lung abscess?

Right side because the bronchi going to the right lobes are more direct (straight) so it's easier to aspirate crap into there. Usually in the upper portion of the right lower lobe, but it depends on the position of the person when they aspirated. Spiking fever with productive cough and foul smelling sputum. CXR shows cavitation with an air/fluid level. Venous clot, most commonly from the femoral vein. Risk factors are Virchow's triad-stasis of blood flow, hypercoagulable states and trauma to the vessel. Clot breaks off and goes to the lung-size of the embolus determines what it will block. Large embolus blocks major vessels (saddle embolus) while small emboli occlude medium and small vessels. Increase in pulmonary artery pressure, decreased flow to pulmonary parenchyma which can cause hemorrhagic infarct, see a red-blue, raised, wedge shaped area that extends to the pleural surface. Fibrinous exudate on the pleural surface and hemorrhagic pleural effusion. Sudden increase in PA pressure which can cause right ventricular failure, sudden onset of dyspnea and tachypnea, fever, pleuritic chest pain, plueral friction rub, pleural effusion, expiratory wheezing from release of TXA2 from platelets. Respiratory alkalosis (PCO2<33mmHg), PaO2<80 mmHg, increased A-a gradient, increased D-Dimer Wedge shaped area of consolidation/infarction from PE

What is the pathophysiology of a pulmonary thromboembolism?

What are consequences of pulmonary thromboembolism?

What are clinical signs of pulmonary thromboembolism? What are lab findings of pulmonary thromboembolism? What is Hampton's Hump?

Define Pulmonary Hypertension What causes primary pulmonary hypertension?

Mean pulmonary artery pressure >25 mmHg at rest or >30mmHg with exercise. Mutation associated with TGF-B resulting in vascular hyperreactivity with proliferation of smooth muscle Endothelial cell dysfunction, e.g. loss of vasodilation (NO), increase in vasoconstriction (endothelin). Hypoxemia and respiratory acidosis stimulate vasoconstriction of pulmonary arteries resulting in smooth muscle hyperplasia and hypertrophy. Any sort of lung disease that results in chronic hypoxemia or chronic respiratory acidosis can do this, e.g. high altitude, chronic bronchitis, sleep apnea, loss of pulmonary vasculature from emphysema or recurrent PE, left to right shunting/volume overload, mitral stenosis resulting in volume overload. Exertional dyspnea (common), chest pain, tapering of arteries on CXR, accentuated P2, left parasternal heave or other signs of right ventricular hypertrophy. Diuretics, O2, vasodilators-Ca channel blockers, prostanoids, endothelin receptor antagonists, lung transplant Pulmonary hemorrhage with hemoptysis often preceding renal failure. Autoantibodies to Type IV collagen in basement membrane of lung and glomerulus. Chest wall disorders with normal lungs, e.g. kyphoscoliosis, pleural disease like mesothelioma or obesity. Acute or chronic interstitial lung diseases, e.g. ARDS, pneumoconiosis or other fibrosing disorders, granulomatous diseases like amyloidosis or sarcoidosis.

What causes secondary pulmonary hypertension? What are clinical findings of pulmonary hypertension? How do you treat pulmonary hypertension? What is Goodpasture's Syndrome?

What are common causes of restrictive lung disease?

What is the pathogenesis of interstitial fibrosis? What are clinical findings in restrictive lung disease?

Elveolitis-leukocytes release cytokines which stimulate fibrosis. Causes functional loss of type I/II pneumocytes and capillaries (decreased DLCO), and decreased expansion of lung parenchyma during inspiration. Increased elasticity to recoil on expiration is increased. dry cough and exertional dyspnea, late inspiratory crackles in lower lung fields, potential cor pulmonale, equal decreases on PFT's. Inhalation of mineral dust into the lungs leading to interstitial fibrosis. Can be silica, asbestos, beryllium or others. "I think I've got the black lung pop" Coal dust, aka aanthracotic pigment comes from coal mines, large cities, second hand smoke, etc. Deposits in alveolar macrophages creating "dust cells." Fibrotic opacities smaller than 1 cm in upper lobes and coal deposits adjacent to respiratory bronchioles producing centriacinar emphysema- simple CWP. Complicated CWP involves large fibrotic opacities, crippling lung disease (black lung), may have cor pulmonale or large cavitating rheumatoid nodules (Caplan Syndrome). No increase in TB or primary lung cancers. Common occupational disease from quartz/silicon dioxide, foundries, sandblasting and working in mines. Quartz is fibrogenic and deposits in the upper lungs, activates and is cytolytic to alveolar macrophages. Macrophages release cytokines resulting in fibrosis.

What is a pneumoconiosis?

Describe Coal Worker's Pneumoconiosis.

What is silicosis?

Describe clinical findings in silicosis.

Ground glass appearance on CXR or nodular opacities in more advanced disease (concentric layers of collagen w/wo central cavitation). Dystrophic calcification of lymph nodes. Can cause cor pulmonale or Caplan syndrome and increased risk of lung cancer and TB. Serpentine asbestos-interstitial fibrosis and lung cancer; amphilobe asbestos-interstitial fibrosis, lung cancer and mesothelioma. Deposits in respiratory bronchioles, alveolar ducts and alveoli. Comes from insulating pipes, naval shipyards, roofing material, ceiling tiles, old floor tiles and demolition of old buildings. Fibers are coated in iron and protein (ferruginous bodies) which are then pahgocytosed, coated with ferritin and look golden and beaded in sputum or distal small airways. Causes calcified pleural plaques which don't predispose to mesothelioma, diffuse interstitial fibrosis, primary bronchogenic carcinoma (esp if smoker), malignant mesothelioma of the pleura arising from serosal cells of the pleura. Can cause cor pulmonale or Caplan syndrome. Beryllium exposure from nuclear and aerospace industry causes diffuse interstitial fibrosis with noncaseating granulomas. Increased risk for cor pulmonale and primary lung cancer.

How do asbestos related diseases occur?

What is the pathogenesis of asbestos related disease?

What is Berylliosis?

What is Sarcoidosis?

Multisystem granulomatous disease of unknown origin. Common in Black women and nonsmokers and causes 25% of chronic interstitial lung disease. Granulomas in mediastinal/hilar lymph nodes and interstitium. Granulomas contain multinucleated giant cells, laminated calcium concretions (Schaumann bodies) and stellate inclusions (asteroid bodies). Dyspnea is the most common symptom. Nodular lesions containing granulomas, violaceous rash on the nose and cheeks (lupus pernio), erythema nodosum-painful nodules on lower extremities, inflammation of subcutaneous fat. Eye lesions produce uveitis, blurry vision, glaucoma and corneal opacities. Can ahve granulomatous hepatitis, enlarged salivary and lacrimal glands, diabetes insipidus, and granulomas in the bone marrow and spleen. See increased ACE, hypercalcemia (increased 1-alpha hydroxylase in granulomas), polyclonal gammopathy, and cutaneous anergy of skin antigens like Candida (due to consumption of CD4+ T cells in granulomas) Idiopathic means the doctor is an idiot!!! Repeated cycles of alveolitis, release of cytokines producing interstitial fibrosis, alveolar fibrosis leading to proximal dilation of small airways giving the lung a honeycomb appearance. See fever, dyspnea on exertion, chronic, nonproductive cough, and late inspiratory crackles. Systemic Lupus causes interstitial disease in 50% of patients and pleuritis with effusion (serositis). Rheumatoid Arthritis can cause rheumatoid nodules (if with a pneumoconiosis, Caplan's syndrome).

What are other clinical signs in Sarcoidosis?

What is idiopathic pulmonary fibrosis? What collagen vascular diseases cause lung disease?

What is hypersensitivity pneumonitis?

Extrinsic allergic alveolitis associated with exposure to known inhaled antigen. Does not involve IgE or have eosinophilia. Exposure to thermophilic actinomyces (Saccharopolyspora rectivirgula) in moldy hay causes precipitating IgG antibodies which combine with inhaled antigens to form immune complexes. Type III hypersensitivity. Immune complexes deposit in lung and cause inflammation which chronically causes granulomatous inflammation (type IV hypersensitivity). Inhalation of gases (oxides of nitrogen) from plant material causes an immediate hypersensitivity reaction associated with dyspnea. Contact with cotton, linen and hemp in textile factories causes exposure to gram negative endotoxin growing on the cotton. Causes dyspnea on exposure to cotton, linen or hemp. Disease occurs on returning to work-Monday Morning Blues (cyanosis) Amiodarone, Bleomycin and Busulfan, Cyclophosphamide, Methotrexate and methysergide, nitrosurea and nitrofurantoin. Obstruction to airflow out of the lungs. Usually loss of elastic recoil or obstruction of airways. Permanent enlargement of all or part of the respiratory unitrespiratory bronchioles, alveolar ducts and alveoli. Smoking is the most common cause. Also can be from Alpha-1 Antitrypsin deficiency

What is Farmer's Lung?

What is Silo Filler's Disease?

What is Byssinosis? What drugs are associated with interstitial fibrosis? What is obstructive lung disease? What is Emphysema? What causes Emphysema?

What is the pathogenesis of Emphysema?

What is the normal function of elastic fibers in the lung?

Where is the site of obstruction in emphysema? What type of Emphysema is most common in smokers?

Increased compliance and decreased elasticity (C=V/P). There can be an imbalance between elastase and anti-elastases (A1AT), or an imbalance between oxidants and antioxidants. Elastase and oxidants all derive from macrophages so chronic inflammation results in tissue destruction. Smoking produces a functional A1AT deficiency. Fibers attach to the outside of the walls of small airways and provide radial traction to keep the lumen open. Destruction causes loss of radial traction and small airway collapse, especially on expiration. During expiration, the distal terminal bronchioles collapse preventing egress of air. Trapped air distends parts of the respiratory unit that have no elastic tissue. Trapped air increases TLC and RV Centriacinar/Centrilobular. Mostly apical segments of upper lobes, distal terminal bronchioles and respiratory bronchioles lose elastic tissue. Panacinar emphysema. Autosomal dominant disorder. MM phenotype is normal, Homozygous ZZ phenotype causes disease. Primarily affects the lower lobes. Tissue destruction happens in distal terminal bronchioles and all parts of the respiratory units. See absent alpha-1 globulin peak in serum protein electrophoresis. Dyspnea is sever and occurs early, causes pink puffers. Frequently coexists with chronic bronchitis.

What type of Emphysema is most common in Alpha-1 Antitrypsin deficiency?

What are 2 non-obstructive types of Emphysema? What is Chronic Bronchitis?

Paraseptal emphysema-localized to the subpleura and targets alveolar ducts and alveoli. Increased incidence of spontaneous pneumothorax from rupture of subpleural blebs. Irregular Emphysema-localized disease associated with scar tissue. Productive cough for at least 3 months. Most commonly from smoking and Cystic Fibrosis. Hypersecretion of mucous in bronchi, obstruction to airflow in the terminal bronchioles, proximal to the obstruction seen in emphysema. Causes irreversible fibrosis of terminal bronchioles. Hypersecretion of submucosal mucus-secreting glands in the trachea and bronchi are responsible for sputum overproduction. Acute inflammation with neutrophils are superimposed on chronic inflammation. Causes loss of ciliated epithelium resulting in squamous metaplasia. Mucus plugs can block the exodus of CO2. GOblet cell metaplasia is seen with hypertrophy of mucus secreting glands, fibrosis and narrowing of the airway. Productive cough, dyspnea late in the disease, cyanosis of skin and membranes, decreased SaO2 from hypoxemia. These patients are called Blue Bloaters. Tend to be stocky or obese, have expiratory wheezing and siliant rhonchi and often cor pulmonale. Also have chronic respiratory acidosis with increased bicarb to compensate. Episodic and reversible obstructive airway disease. Primarily targets bronchi and terminal bronchioles.

What is the pathogenesis of chronic bronchitis?

What changes are seen in the bronchi with chronic bronchitis?

What are clinical findings of chronic bronchitis? What is Asthma?

What is Extrinsic Asthma? What are other chemical mediators involved in Extrinsic Asthma?

Type I hypersensitivity reaction with exposure to extrinsic allergens, typically in children with atopic family history. Initial sensitization to inhaled allergens stimulates induction of Th2 cells which release IL-4 and IL-5. IL-4 facilitates isotype switching to IgE and IL-5 stimulates production and maturation of eosinophils. Inflammatory mediators like histamine facilitate bronchoconstriction, mucus production and influx of leukocytes. Later Eotaxin is released which recruits eosinophils. Eosinophils release major basic protein which damages epithelial cells and produces airway constriction. Leukotriene C, D, E4 cause prolonged bronchoconstriction. Acetylcholine causes airway muscle contraction. Thickening of the basement membrane, edema and mixed inflammatory infiltrate, hypertrophy of submucosal glands and hypertrophy/hyperplasia of smooth muscle cells. Also see spiral shaped mucus plugs which contain old epithelial cells-Curschmann Spirals. This is a pathologic effect of major basic protein. Crystalline granules in eosinophils coalesce to form Charcot-Leyden crystals. Episodic wheezing, nocturnal cough, increased AP diameter from air trapping. Initially have respiratory alkalosis but may turn into respiratory acidosis if bronchospasm is not relieved. Nonimmune asthma caused by virus-induced respiratory infection, or air pollutants. Permanent dilation of bronchi and bronchioles due to destruction of cartilage and elastic tissue by chronic necrotizing infections.

What are some histologic changes in Extrinsic Asthma?

What are clinical findings in Extrinsic Asthma? What is Intrinsic Asthma?

What is Bronchiectasis?

What are some causes of Bronchiectasis? What are some clinical findings in Bronchiectasis?

Cystic Fibrosis, Infection (TB, adenovirus, staph, HiB), bronchial obstruction (bronchogenic carcinoma), Primary ciliary dyskinesia (absent dynein arm in cilia aka Kartagener's Syndrome), Allergic Bronchopulmonary Aspergillosis. Cough productive of massive amounts of sputum, hemoptysis, digital clubbing, cor pulmonale, crowded bronchial markings that extend to lung periphery. Autosomal Recessive disease. Three nucleotide deletion on chromosome 7(should be phenylalanine) resulting in defective CF transmembrane conductance regulator (CFTR) for chloride ions. Defective protein is degraded in the Golgiso there is decreased reabsorption of Na+ and Cl- from sweat glands, but decreased secretion of Na and Cl into luminal secretions. This results in dehydrated body secretions which are thick and easily infected. Nasal polyps, heat exhaustion, respiratory infections/failure, cor pulmonale, pneumothorax, malabsorption, type I diabetes from pancreatic destruction, infertility in males (atresia of vas deferens), meconium ileus, rectail prolapse from straining, gallstones from thick bile and secondary biliary cirrhosis. Smoking, Radon gas (uranium mining), asbestos, metal exposurechromium, cadmium, beryllium, arsenic- secondhand smoke, ionizing radiation, air pollution, prior TB Most common tumor, weakest smoking association, tends to be peripherally located bc filters in cigarettes remove large carcinogens leaving the small ones that can move peripherally.

What is Cystic Fibrosis?

What are clinical findings in CF?

What are risk factors for lung cancer?

What are some features of adenocarcinoma?

What are some features of squamous cell carcinoma? What are common sites for metastasis? Which cancers are most commonly responsible for lung metastasis? Where in the lung do tumors commonly metastasize? What are common findings in primary lung cancer?

2nd most common tumor, greatest smoking association. Tends to be centrally located (mainstem bronchus) Hilar lymph nodes (most common), adrenal glands, liver, brain, bone

Primary breast cancer, colon cancer and renal cell carcinoma. Parenchyma, pleura and pleural space (pleural effusions), lymphatics (causes severe dyspnea) Cough, weight loss, chest pain, hemoptysis, dyspnea, superior vena cava syndrome Superior sulcus tumor. Usually a primary squamous cancer located at the extreme apex of the lung. Causes desctruction of superior cervical sympathetic ganglion producing Horner's syndrome. Digital clubbing from reactive periosteal changes in underlying bone. Muscle weakness (Eaton Lambert Syndrome). Ectopic hormone secretion (ACTH) Usually metastatic primary lung cancer in older patients, usually a primary disease in younger patients. Neurogenic tumors (posterior mediastinum)- neuroblastoma (malignant in children), ganglioneuroma (benign in adults). Thymomas, pericardial cysts, malignant lymphomas (anterior mediastinum, usually nodular sclerosing Hodgkin's in a woman), teratomas-usually benign, in anterior mediastinum.

What is a Pancoast tumor? What are some paraneoplastic changes associated with lung cancers?

What are the common causes of mediastinal masses?

What are some symptoms of Thymoma?

Thymoma is usually benign (70%) neoplastic epithelial tissue. Most patients have systemic symptoms of Myesthenia Gravis. Most commonly have follicular B cell hyperplasia in the thymus (that's where antiacetylcholine antibodies are synthesized). Also can have hypogammaglobulinemia, RBC aplasia and increased incidence of other autoimmune diseases. Increased hydrostatic pressure in visceral pleura (CHF), decreased oncotic pressure (nephrotic syndrome), obstruction of lymphatic drainage from pleura (lung cancer), increased vessel permeability of pleural capillaries (pulmonary infarction, pneumonia), metastasis to the pleura (metastatic breast cancer). Ultrafiltrate of plasma from disturbances in Starling pressures (CHF, nephrotic syndrome) Protein-rich and cell-rich fluid from increased vessel permeability. Indicates interruption of the thoracic duct. Turbid, milky appearance. Can be from malignancy, trauma (iatrogenic) or too many chylomicrons Turbid, milky appearance from increased inflammation with necrotic debris. Most often from rheumatoid lung disease. Ratio of pleural fluid protein and LDH to serum protein and LDH. PF protein/serum protein <0.5 is transudate, >0.5 is exudate. PF LDH/serum LDH <0.6 is transudate, >0.6 is exudate. PF LDH <200 U/L is transudate, >200 U/L is exudate

What is the etiology of pleural effusions? Describe a transudate Describe an exudate

Describe Chylous fluid Describe Pseudochylous fluid

How do you distinguish between exudate and transudate?

How does a spontaneous pneumothorax happen?

Commonly seen in tall, thin young men, 20-40 yrs old, increased risk with smoking. Can be caused by rupture of apical subpleural blebs (secondary to high negative intrapleural pressure), COPD, Marfan syndrome, scuba diving, insertion of a subclavian catheter. Loss of negative intrapleural pressure causes collapse of lung. Sudden onset of dyspnea with pleuritic chest pain. Penetrating trauma to the lungs, rupture of tension pneumocytes. Flap like tear in pleura allows air into pleural cavity but prevents its release resulting in increasing positive intrapleural pressure. This results in compression atelectasis. Sudden onset of severe dyspnea and plueritic chest pain, can cause trachea and mediastinal structures to deviate to contralateral side. Can cause compromised venous return to the heart.

What is the pathogenesis of a Tension Pneumothorax?

Reproductive
What vein drains the ovaries/testes? What is the lymphatic drainage of the Ovaries/Testes? Where does lymph from the vagina/vulva/scrotum drain to? What does the suspensory ligament of the ovaries connect? What does the Cardinal ligament connect? What does the Round ligament of the uterus connect? What is the round ligament of the uterus derive from? What does the Broad Ligament connects? What does the Ligament of the ovary connect? What does the Genital Tubercle become? What does the Urogenital Fold become? What does the labioscrotal swelling become? What is the pathway of sperm during ejaculation? Left Gonadal vein to the left renal vein to the IVC. Right ovary/testis drains to right gonadal vein straight to the IVC. Ovary/Testis drains to the para-aortic lymph nodes. Distal 1/3 of the vagina/vulva/scrotum drains to the superficial lymph nodes. Proximal 2/3 of vagina/uterus drains to the obturator, external iliac and hypogastric lymph nodes Connects ovaries to the lateral pelvic wall and contains the ovarian vessels. Connects the cervix to the side wall of the pelvis and contains the uterine vessels. Contains the Uterine fundus to the labia majora but carries no structures. Derivative of the Gubernaculum. Travels through the round inguinal canal. Connects the uterus, fallopian tubes, and ovaries to the pelvic side wall. Contains the ovaries, fallopian tubes, and round ligaments of the uterus. Connects the ovary to the uterus and does not contain any structures. Becomes the Glans Penis or Clitoris Becomes the shaft of the penis or the labia minora Scrotum and Labia majora (SEVEN UP) Seminiferous tubules to epididymis to vas deferens to ejaculatory ducts (nothing) to urethra to the penis Erection-Parasympathetic nervous system (pelvic nerve). Nitric oxide increases cGMP which causes smooth muscle relaxation which causes vasodilation and is proerectile. Also Norepinephrine causes an increase in Calcium which causes smooth muscle contraction which causes vasoconstriction and is antierectile.

What is the autonomic innervation causing an erection? What is the autonomic innervation causing Sperm Emission? What is the autonomic innervation causing Ejaculation? What are the different parts of the sperm? Where do the different parts of the sperm come from?

Sympathetic nervous system via the hypogastric nerve Visceral and somatic via the pudendal nerve Acrosome, head, nucleus, neck, middle piece, tail Acrosome-Golgi apparatus, Flagellum/Tail-Centrioles, Middle Piece-contains the mitochondria, Head and nucleus come from the nucleus.

What is the function of spermatogonia?

What is the function of Sertoli Cells? What is the function of Leydig Cells? What is the composition of Semen? Describe the general process of spermatogenesis What is spermiogenesis?

Maintain the germ pool and produce primary spermatocytes Secrete inhibin which inhibits FSH. Secrete Androgen Binding Protein to maintain the level of testosterone. Form tight junctions between adjacent Sertoli Cells to form the blood-testis barrier, isolating gametes from immune attack. Support and nourish spermatozoa. Regulate spermatogenesis. Produce Anti-Mullerian hormone. Secrete testosterone Seminal Vesicle Products(fructose, ascorbic acid, prostaglandins, phosphorylcholine, flavins), Prostate Products (Zinc, citrate acid, phospholipids, acid phosphatase, fibrinolysin), Sperm Spermatogenesis begins at puberty with spermatogonia. Full development takes 2 months. Occurs in seminiferous tubules. Produces spermatids that undergo spermiogenesis to form mature spermatozoa Maturation of sperm as they lose their cytoplasmic contents, gain an acrosomal cap and become mature spermatozoa Spermatogonium (diploid 2N) copies genome to make Primary spermatid (Diploid 4N). Primary spermatocyte divides into 2 secondary spermatocytes (Haploid 2N). The Secondary spermatids divide again to produce 4 spermatids (Haploid, 1N). These undergo spermiogenesis to form mature spermatozoa Hypothalamus releases GnRH which causes FSH and LH release from the anterior pituitary. LH stimulates testosterone release from Leydig cells which release testosterone into the seminiferous tubules and the blood. FSH stimulates Sertoli cells to produce Androgen Binding Protein and Inhibin. Testosterone from the Leydig cells stimulates spermatogenesis and stimulates the Sertoli Cells to nurse the Spermatozoa. Inhibin from the Sertoli cells feeds back and downregulates FSH release. Testosterone from Leydig cells feeds back and downregulates LH production and GnRH release. Testosterone (Testes), Dihydrotestosterone (Converted peripherally) and Androstendione (Adrenal) Differentiation of the Epididymis, Vas deferens and seminal vesicles. Growth spurt of the penis, the seminal vesicles, sperm, muscle, and red blood cell growth. Deepening of voice, closing of epiphyseal plates (via estrogen converted from testosterone) and Libido. In early differentiation it causes development of the penis, scrotum and prostate. In later/pubertal development it causes prostate growth and sebaceous gland activity. 5 Alpha reductase converts Testosterone to DHT. Ovary makes 17 Beta estradiol, Placenta makes estriol and blood/peripheral tissues can aromatize androgens to estrogen. Development of genitalia (external) and breast, and female fat distribution.

Describe the process of spermatogenesis.

Describe the hormonal regulation of Spermatogenesis. What are the common Androgens? What are the functions of Testosterone in development? What is the function of Dihydrotestosterone in development? How is testosterone converted to DHT? What are the sources of Estrogen in a woman? What is the function of Estrogen in development?

What are the typical functions of estrogen beyond development? How much do estrogens increase in pregnancy?

Growth of the follicle, endometrial proliferation, increased myometrial excitability. Upregulates LH, FSH and estrogen receptors and thus upregulates itself. Feedback inhibition of LH and FSH and then the LH surge. Stimulates prolactin secretion but blocks its action at the breast. Increases transport of proteins, Steroid hormone binding globulin synthesis, increases HDL and decreases LDL. 50 fold increase in estradiol and estrone. 1000 fold increase in estriol indicates fetal well being. Pulsatile GnRH from the Hypothalamus causes release of FSH and LH from the anterior pituitary. FSH stimulates the granulosa cells of the ovaries to increase Aromatase which can then convert androstendione to estrogen. LH acts on the Theca cells to upregulate Desmolase which convert cholesterol to androstendione. The androstendione goes to the granulosa cells to be converted to estrogen. Corpus Luteum, placenta, adrenal cortex and testes (in men obviously) Ovulation!!! Stimulation of endometrial glandular secretions and spiral artery development. Maintains pregnancy. Decreases myometrial excitability. Increases production of thick cervical mucous, which inhibits sperm entry into the uterus. Increases body temperature (hence why you take your temp), inhibits gonadotropins (LH and FSH), relaxes uterine smooth muscle (prevents contraction) and decreases estrogen receptor expressivity. Granulosa cells respond to FSH and stimulate growth of 10-20 follicles. LH responsive Theca cells stimulate growth of the corpus luteum and produce androgens which are converted to estrogen by granulosa cells (to stimulate the developing follicle). Estrogen encourages growth of the endometrium and provides positive feedback to the anterior pituitary to stimulate release of more FSH/LH leading to the midcycle gonadotropin surge. About 1 week before ovulation, one follicle becomes dominant meaning that it becomes more responsive to FSH. The follicle secretes lots of inhibin which downregulates FSH and causes atresia of the other follicles. 2nd week of the proliferative phase. Estrogen Progesterone Cycle greater than 35 days Cycle less than 21 days Frequent but irregular menstruation Heavy, irregular menstruation

Describe the hormonal regulation of estrogen. What is the source of Progesterone? What does elevation of progesterone indicate?

What is the function of Progesterone?

What happens during the proliferative/follicular phase of a woman's cycle? When is follicular growth fastest? What stimulates endometrial proliferation? What What What What What maintains the endometrium? defines Oligomenorrhea? defines Polymenorrhea? defines Metorrhagia? defines Menometrorrhagia?

Describe the hormonal changes during a woman's cycle (see Reproductive Attachment 1).

During the follicular phase, both estrogen and progesterone are low. FSH is fairly low as is LH initially. LH spikes about halfway through the follicular phase which increases estrogen above its threshold. Estrogen feeds back onto LH which causes it to spike along with an estrogen spike. FSH is also increased and has a small spike along with the LH spike. This causes ovulation and begins the secretory/luteal phase. LH and FSH then drop. Estrogen increases again but Progesterone increases a lot throughout the whole phase thus maintaining the lining of the endometrium. Everything drops when entering the menstrual phase which allows the endometrial llining to shed. A primordial follicle consists of an oocyte surrounded by a single layer of squamuos granulosa cells. The granulosa cells enlarge and become cuboidal turning the follicle into a primary follicle. The primary follicle then enlarges and the granulosa cells form more than one layer. The Zona Pellucida then forms around the oocyte. The structure becomes a secondary follicle when fluid filled vesicles develop among the granulosa cells and a well developed capsule, Theca layer, becomes apparent around the granulosa cells. The Theca has both internal and external layers. It becomes a mature follicle when the vesicles form a single antrum. At full maturity, the oocyte is located in the cumulus mass. During ovulation, the oocyte is released with some granulosa cells called the corona radiata. The remaining granulosa cells divide rapidly and enlarge to form the corpus luteum which makes progesterone for the remainder of the cycle or the beginning of pregnancy. The corpus luteum then degenerates to form the corpus albicans and eventually becomes fibrotic. Increased estrogen, increased GnRH and increased GnRH receptors on anterior pituitary, estrogen surge precedes LH surge. Increased temperature from increased progesterone. Blood from ruptured follicles which can cause peritoneal irritation that mimics appendicitis. Primary oocytes begin Meiosis I during fetal life but don't complete Meiosis I until just before ovulation. Thus Meiosis I is arrested in Prophase for years until ovulation. Meiosis II arrests in metaphase until fertilization. If there is no fertilization, the secondary oocyte degenerates. Begins with a diploid Oogonium (2N) which replicates (interphase) to become a diploid primary oocyte (4N). The Primary oocyte then arrests in Prophase I until ovulation. During ovulation it divides to become a secondary haploid oocyte (2N) and a polar body which degenerates. It arrests in Metaphase II here until fertilization. The secondary Oocyte divides again to become a Haploid Ovum (1N) and another polar body that degenerates. Most commonly happens in the upper end of the Fallopian tube (the ampulla). Typically within a day after ovulation. 6 days after fertilization. The trophoblast secretes Beta-HCG which is detectable in the blood 1 week after conception and in urine (home test) 2 weeks after conception. The decrease in maternal steroids induces lactation. Suckling increases nerve stimulation which increases oxytocin and prolactin production thus maintaining milk production. PRL induces and maintains lactation and decreases reproductive function.

Describe the maturation of the Follicle (see Reproductive Attachment 2).

What happens to the follicle during ovulation? What hormonal changes are seen during ovulation? What is Mittelschmerz? When does oogenesis begin and when is it completed?

What is the process of oogenesis? Where does Fertilization most commonly happen? When does implantation into the wall of the uterus typically occur? How is lactation induces after labor? How is milk production maintained after birth? What is the role of Prolactin in the female?

What is the role of Oxytocin in the female? Where is hCG made?

Helps with milk letdown and may be involved with uterine contractions. Syncytiotrophoblast of the placenta. Maintains corpus luteum (thus progesterone) for the first trimester by acting LH. The Placenta synthesizes its own estriol and progesterone during the 2nd and 3rd trimester and the corpus luteum degenerates. hCG is used to detect pregnancy because it appears early in the urine. hCG is elevated in Hydatidiform moles, Choriocarcinoma, Gestational trophoblastic tumors (and other tumors I think) Decreased Estrogen production due to age linked decline in follicles. Significantly increased FSH, increased LH, increased GnRH. Average age of onset is 51, earlier in smokers. Usually preceded by a few years of irregular periods. Estrone from peripheral conversion of androgens. Increased androgens can cause hirsutism (that's why your grandma has a mustache) HHAVOC-Hirsutism, Hot flashes, Atrophy of the Vagina, Osteoporosis, Coronary artery disease 47 (XXY). Causes testicular atrophy, eunuchoid body shape, tall, long extremities, gynecomastia, female hair distribution. May cause developmental delay. Usually a Barr body is present (inactive X chromosome) Dysgenesis of seminiferous tubules causes decreased inhibin which leads to increased FSH. Abnormal Leydig cell function causes decreased testosterone and increased LH and estrogen. 45 (XO). Causes short stature, ovarian dysgenesis (streak ovaries), shield chest, bicuspid aortic valve, webbing of the neck from cystic hygroma, preductal coarctation of the aorta, no Barr body and primary amenorrhea. 47 (XYY). Phenotypically normal, very tall, severe acne, antisocial behavior in 1-2%, normal fertility.

What is the function of hCG? How is pregnancy detected? What changes in hCG are there in pathologic states? What hormonal changes are seen in menopause? What is the main source of Estrogen after menopause? What are some symptoms of menopause?

What is Klinefelter's Syndrome? How does Klinefelter's Syndrome cause infertility?

What is Turner's Syndrome? Describe a double Y male What hormonal changes would you see with a defective androgen receptor? What hormonal changes would you see with a Testosterone-secreting tumor, or exogenous steroids What hormonal changes would you see with primary hypogonadism? What hormonal changes would you see with Hypogonadotropic hypogonadism? What is pseudohermaphroditism?

Increased testosterone and increased LH (female phenotype I think)

Increased testosterone but decreased LH from negative feedback

Decreased testosterone and increased LH from gonadal failure and lack of feedback.

Decreased testosterone and decreased LH from pituitary failure not stimulating the gonads. Disagreement between the phenotypic (external genitalia) and gonadal (testes vs ovaries) sex.

What is a female pseudohermaphrodite? What is a male pseudohermaphrodite? What is a true hermaphrodite?

What is Androgen Insensitivity Syndrome?

46 (XX). Ovaries are present but the external genitalia are virilized or ambiguous. It's due to excessive or inappropriate androgen exposure during early gestation. Usually congenital adrenal hyperpasia or exogenous androgen administration. 46 (XY). Testes are present but external genitalia are female or ambiguous. The most common reason is androgen insensitivity syndrome aka testicular feminization. (46, XX or 47, XXY). Both ovaries and testicular tissue present. Ambiguous genitalia. Very rare. Defect in androgen receptors resulting in normal-appearing female. Female external genitalia with a rudimentary vagina. Uterus, uterine tubes are generally absent. No sexual hair. Testes are often found in the labia majora and must be surgically removed to prevent malignancy. Increased testosterone (although no response), increased estrogen and LH Inability to convert testosterone to DHT. Ambiguous genitalia until puberty when the massive testosterone increase causes masculinization and increased growth of the external genitalia. Testosterone/estrogen levels are normal; LH is normal or increased. Internal genitalia are normal. Cystic Swelling of chorionic villi and proliferation of chorionic epithelium (trophoblast) that presents with abnormal vaginal bleeding. Most common cause of Choriocarcinoma. See increased Beta-hCG, a honeycombed uterus, looks like a cluster of grapes (if a cluster of grapes is totally disgusting looking). See an abnormally enlarged uterus. 2 sperm with a completely empty egg. Classically have a snowstorm appearance with no fetus during first sonogram. Moles can lead to uterine rupture. Treat with dilitation and curettage and methotrexate. Monitor Beta-hCG. Karyotype is 46,XX or 46, XY. Massively increased hCG, increased uterine size, 2% convert to adenocarcinoma, no fetal parts, 2 sperm +empty egg, 15-20% form malignant trophoblastic disease. Karyotype is 69,XXY, slightly increased hCG, no change in uterine size, rare for it to convert to choriocarcinoma, 2 sperm+1 egg, risk of malignancy is less than 5% during the 1st weeks- low progesterone levels (no response to Beta-hCG, 1st trimester-chromosomal abnormalities, 2nd trimester-bicornate uterus Combination of hypertension, proteinuria and edema. Pre-eclampsia + Seizures Pre-existing hypertension, diabetes, chronic renal disease and autoimmune disorders. Caused by placental ischemia due to impaired vasodilation or spiral arteries, resulting in increased vascular tone. May be an issue with implantation. Hemolysis, Elevated LFT's, Low Platelets from Pre-eclampsia Headache, blurred vision, abdominal pain, edema of the face and extremities, altered mentation, hyperreflexia. Lab findings include thrombocytopenia and hyperuricemia. Delivery of the fetus as soon as it's viable. Otherwise bed rest, salt restriction, and monitoring/treatment of hypertension. Treatment is IV magnesium sulfate and diazepam to prevent seizures of eclampsia.

What is 5 alpha reductase deficiency?

What is a Hyaditiform Mole?

What is a complete Hyaditiform Mole? What characteristics are seen in a complete mole? What characteristics are seen in a partial mole? What are some common causes of recurrent miscarriages? What is pre-eclampsia? What is eclampsia? What are some risk factors for preeclampsia? What is the pathogenesis of Preeclampsia? What is HELLP Syndrome? What are some clinical features of Preeclampsia? How do you treat Pre-Eclampsia or Eclampsia?

What is Abruptio Placentae?

What is Placenta Acreta? What is Placenta Increta?

Premature detachment of the the placenta from the implantation site. Fetal death and DIC may occur. Increase in risk with smoking, hypertension and cocaine use. Defective decidual layer allows the placenta to attach to the myometrium. No separation of the placenta after birth. May cause massive bleeding after delivery. Associated with prior C-Section. Acreta does not penetrate the entirety of the myometrium. Just like Placenta Acreta but extends further into the myometrium. The worst form of Placenta Acreta which involves the placenta extending all the way through the myometrium to the serosa. The placenta may then attach to other organs like the bladder or rectum. Attachment of the placenta to the lower uterine segment. May then occlude the internal os (so baby can't get out). Associated with multiparity and prior C-Section. Pregnancy that isn't in the uterus. Most often in the Fallopian tubes. Suspect with increased hCG and sudden lower abdominal pain. Confirm with ultrasound. May be clinically mistaken for appendicitis. May cause postpartum hemorrhage. History of infertility, Salpingitis/PID, ruptured appendix (at any point), prior tubal surgery or any lower abdominal surgery, endometriosis. Greater than 1.5-2 Liters of amniotic fluid. Associated with esophageal and duodenal atresia, causing inability to swallow amniotic fluid. Also associated with anencephaly. Less than 0.5 Liters of amniotic fluid. Associated with placental insufficiency, bilateral renal agenesis or posterior urethral valves (in men) and thus an inability to excrete urine. Can cause Potter's syndrome. Atypical appearance of the fetus in the womb as a result of oligohydramnios. Causes clubbed feet, pulmonary hypoplasia and cranial anomalies. Disordered epithelial growth. Begins at the basal layer of the squamo-columnar junction and extends outward. Classified as CIN I, CIN II or CIN III (Carcinoma in Situ), depending on the extent of the dysplasia. HPV 16 and 18 Multiple sexual partners, smoking, early sexual intercourse, HIV infection Pretty much the cervical cancer gone really nasty. Often squamous cell carcinoma. Papsmear can catch cervical dysplasia (koilocytes) before it becomes invasive carcinoma. Lateral invasion can block ureters causinf renal failure. Cervical cell infected with HPV that is undergoing dysplasia. See large nuclei and large ring of cytoplasm. See Attachment 3 for some pics.

What is Placenta Percreta? What is Placenta Previa?

What is an Ectopic Pregnancy? What is the problem with retained placental tissue? What are some risk factors associated with ectopic pregnancy? What is Polyhydramnios?

What is Oligohydramnios? What is Potter's Syndrome? Describe Dysplasia and Carcinoma in Situ of the cervix. What virus is associated with Cervical dysplasia? What risk factors are associated with cervical dysplasia? Describe invasice carcinoma of the cervix What is a Koilocyte?

What is Endometriosis? How does Endometriosis manifest clinically? What are possible complications of Endometriosis? What is Adenomyosis? What is Endometrial Hyperplasia? How does Endometrial Hyperplasia manifest clinically and what are some risk factors?

Non-neoplastic endometrial glands/stroma in an abnormal location outside the uterus. Characterized by cyclic bleeding from the ectopic endometrial tissue resulting in blood filled "chocolate cysts." Does anyone else want to puke right now? Often in the ovary or on the peritoneum. Severe menstrual-related pain. Often causes infertility, possibly due to retrograde mentrual flow or ascending infection. Endometrium within the myometrium Abnormal endometrial gland proliferaton usually caused by excess estrogen stimulation. Associated with increased risk for endometrial carcinoma. Postmenopausal vaginal bleeding. Risk factors are anovulatory cycles, hormone replacement therapy, polycystic ovarian syndrome and granulosa cell tumors. Most common gynecologic malignancy, usually between 55 and 65 years of age. Usually a progression of endometrial hyperplasia so presents with vaginal bleeding after menopause. Risk factors are prolonged estrogen exposure without progesterone, obesity, diabetes, hypertension, nulliparity and late menopause. The more it's invaded the myometrium, the worse the prognosis. Most common cause of all tumors in females. Essentially a Fibroid. Often causes multiple tumors with well demarcated borders. This is a benign smooth muscle tumor and malignant transformation is very rare. Mostly occurs between 20-40 years old and is often asymptomatic. may cause abnormal uterine bleeding or result in miscarriage. If bleeding is severe it may cause Iron deficiency anemia. See a whorled pattern of smooth muscle bundles (doesn't become Leiomyosarcoma). See attachment 4 for a picture. Bulky, irregularly shaped tumor with areas of necrosis and hemorrhage. Nasty tumor. Typically arises de novo, not from a Leiomyoma. Highly aggressive tumor with a tendency to recur. May protrude out of the cervix and bleed (yuck!). More common in middle aged women and African American women. Incidence- Endometrial>Ovarian>Cervical. Worst Prognosis- Ovarian>Cervical>Endometrial Premature atresia of ovarian follicles in women of reproductive age. Presents with signs of menopause after puberty but before age 40. See decreased estrogen but increased LH and FSH b/c no feedback. Polycystic ovarian syndrome, obesity, Asherman's Syndrome (adhesions), HPO axis abnormalities, premature ovarian failure, hyperprolactinemia, thyroid disorders, eating disorders, Cushing Syndrome and adrenal insufficiency Increased LH production leading to anovulation, hyperandrogenism due to deranged steroid synthesis by theca cells. Enlarged bilateral cystic ovaries manifest clinically with amenorrhea, infertility, obesity and hirsutism. Associated with insulin resistance, increased risk of endometrial cancer. Treatment is weight loss, OCP, gonadotropin analogs, clomiphene or surgery.

What is Endometrial Carcinoma?

Describe a Leiomyoma?

What is a Leiomyosarcoma? What is the epidemiology of gynecologic tumors?

What is premature Ovarian failure? what are the most common causes of anovulation?

What is Polycystic Ovarian Syndrome?

What hormonal changes do you see in PCOS? What is a Follicular Cyst? What is a Corpus Luteum cyst? What is a Theca Lutein Cyst? What is a Chocolate Cyst? What age group most commonly gets Ovarian Cell Tumors? What is a Dysgerminoma?

Increased LH and FSH and increased Testosterone. Distention of a ruptured Grafian Follicle. May be associated with hyperestrinism and endometrial hyperplasia. Hemorrhage into persistent corpus luteum. Commonly regresses spontaneously. Commonly bilateral or multiple cysts. Due to gonadotropin stimulation. Associated with choriocarcinoma and moles. Blood-containing cyst from ovarian endometriosis. Varies with the menstrual cycle. Most common in adolescents Malignant, equivalent to a male seminoma, but rarer (1% vs 30%). Sheets of uniform cells with hCG and LDH. Rare but malignant. Can develop during pregnancy in mother or the baby. Large, hyperchromatic syncitiotrophoblastic cells. Increased frequency of theca-lutein cysts. Along with moles, comprise spectrum of gestational trophoblastic neoplasia. hCG is the tumor marker. Aggressive malignancy in the ovaries (testes in boys) and sacrococcygeal area of young children. These are yellow, friable, solid masses. 50% have Schiller Duval bodies that resemble glomeruli. Alpha fetoprotein is the tumor marker. 90% of ovarian germ cell tumors. Contain cells from 2-3 germ layers. Mature teratomas/Dermoid cysts are the most frequent benign ovarian tumors/teratomas. Immature teratomas are aggressively malignant. Struma Ovarii contain functional thyroid tissue. Can present as hyperthyroidism. Makes up about 20% of ovarian tumors. Frequently bilateral, lined with Fallopian tube-like epithelium. Benign. Makes up about 50% of ovarian tumors, malignant and frequently bilateral. Multilobular cyst lined by mucus-secreting epithelium. Benign. Intestine-like tissue. Malignant! Pseudomyxoma peritonei- intraperitoneal accumulation of mucinous material from ovarian or appendiceal tumor. Benign tumor that looks like the bladder. Bundles of spindle shaped fibroblasts. Associated with Fibromas. Triad of ovarian fibroma, ascites and hydrothorax. Causes pulling sensation in the groin. Secretes estrogen-causes precocious puberty. Can cause endometrial hyperplasia or carcinoma in adults. See Call-Exner bodies-small follicles filled with eosinophilic secretions. Abnormal uterine bleeding. GI Malignancy that metastasizes to the ovaries, causing a mucin-secreting signet cell adenocarcinoma. Secondary to squamous cell carcinoma of the cervix.

What is a Choriocarcinoma? What is a yolk sac (endodermal sinus) tumor?

What is a teratoma? What is a serous cystadenoma? What is a serous cystadenocarcinoma? What is a Mucinous Cystadenoma? What is a Mucinous Cystadenocarcinoma? What is a Brenner tumor? What is a Fibroma? What is Meigs' Syndrome?

What is a Granulosa Cell Tumor? What is a Krukenberg tumor? What causes squamous cell carcinoma of the vagina?

What predisposes to Clear Cell Adenocarcinoma? Who is affected by Sarcoma Botryoides (variant of Rhabdomyosarcoma) How do Bartholin's gland cyst present? What is a Fibroadenoma of the breast? What is an Intraductal Papilloma? What is a Phyllodes Tumor? How do malignant breast tumors arise and when/where are they most common? What are some risk factors for malignant breast tumors? What is a Ductal Carcinom in Situ (DCIS)? What is invasive ductal carcinoma? What is What is breast? What is breast? What is breast? an invasive Lobular tumor? a medullary tumor of the a comedocarcinoma of the an inflammatory tumor of the

Affects women who had exposure to DES in utero.

Affects girls < 4 years of age. Spindle shaped tumor cells that are desmin positive. Rare. Present with pain in the labia majora. Can result from previous infection. Small, mobile, firm mass with sharp edges. Most common tumor in those <25 years. See increasing siza and tenderness with increasing estrogen such as during menstruation. Not a precursor to breast cancer. Small tumor that grows in lactiferous ducts. Typically beneath areola. See serous or bloody nipple discharge. Slight (1.5-2X) increased risk for breast carcinoma. Large bulky mass of connective tissue and cysts with "Leaf like projections." Most common in the 6th decade. Some may become malignant. Common postmenopause. Arise from mammary duct epithelium or lobular glands. Overexpression of estrogen/progesterone receptors on erb-B2 (HER-2 and EGF Receptor) is common. Affects therapy and prognosis. Axillary lymph node involvement is the single most important prognostic factor. Risk factors are increased estrogen exposure. Increased total number of menstrual cycles, older age at 1st live birth, obesity (adipose tissue serves as a major source of estrogen in post-menopausal women by converting androstenedione to estrone). Malignant tumor of the breast that fills the ductal lumen. Arises from ductal hyperplasia. Early malignancy without basement membrane penetration. Worst and most invasive ductal carcinoma but also most common. Forms firm, fibrous, rock hard masses with sharp margins and small, glandular duct like cells. Malignant breast tumor, often multiple and often bilateral. See an orderly row of cells. Malignant tumor with a good prognosis. See fleshy, cellular, lymphatic infiltrate. Subtype of DCIS. See ductal caseous necrosis. Nasty, malignant tumor with a 50% 5 year survival. See dermal lymphatic invasion by breast carcinoma. See Peau d'orange-breast skin looks like orange peel. Eczematous patches on nipples. Paget cells are large cells in the epidermis with clear halo around them. May also be seen on the vulva. Suggests an underlying carcinoma. Most common cause of breast lumps after age 25. Presents with premenstrual breast pain and multiple lesions, often bilaterally. See a fluctuation in size of the mass. Usually does not indicate increased risk of carcinomas.

What is Paget's disease?

What is Fibrocystic disease?

What are the histologic subtypes of Fibrocystic disease? What is acute mastitis? What is Fat Necrosis?

What is Gynecomastia? What is the order of structures in the breast starting at the nipple?

Fibrosis-hyperplasia of breast stroma. Cystic-fluid filled, blue dome. Ductal dilation. Sclerosing adenosisincreases acini and intralobular fibrosis. Associated with calcifications. Epithelial hyperplasia-increase in number of epithelial cell layers in terminal duct lobule. Increases risk of carcinoma with atypical cells. Occurs in women >30 years of age. Breast abscess. During breast feeding. Increases risk of bacterial infection through cracks in the nipple. Staph Aureus is the most common pathogen. A benign, painless lump. Forms as a result of injury to breast tissue. Up to 50% of patients may not report trauma. Results from hyperestrogenism (cirrhosis, testicular tumor, puberty, old age), Klinefelter's syndrome or drugs (estrogen, marijuana, heroin, psychoactive drugs, Spironolactone, Digitalis, Cimetidine, Alcohol, Ketoconazole). Nipple, Lactiferous sinus, major duct, terminal duct, lobules. All surrounded by stroma Nipple-Paget's disease, breast abscesses. Lactiferous sinus-Intraductal papilloma, breast abscess, mastitis. Major duct-Fibrocystic change, ductal cancer. Terminal ducts-Tubular carcinoma. Lobules-lobular carcinoma, sclerosing adenitis. Stroma-Fibroadenoma, phyllodes tumor. Dysuria, frequency, urgency, low back pain. Usually bacterial, especially E. Coli May be bacterial or abacterial. Hyperplasia (not hypertrophy) of the prostate gland. May be due to an age related increase in estradiol with possible sensitization of the prostate to the growth-promoting effects of DHT. Characterized by a nodular enlargement of the periurethral (lateral and middle) lobes, which compress the urethra into a vertical slit. Often present with increased frequency of urination, nocturia, difficulaty starting and stopping the stream of urine and dysuria. May lead to distention and hypertrophy of the bladder, hydronephrosis and UTI's. Not considered premalignant. Do see increased free PSA but not rapidly increasing like in cancer. Use alpha antagonists like Terazosin, tamulosin, which cause relaxation of smooth muscle. Common in men >50. Arises most frequently from the posterior lobe of the prostate(peripheral zone) and is most commonly diagnosed by digital rectal exam and prostate biopsy. Prostatic acid phosphatase and PSA are the most useful tmor markers. See increased total PSA with decreased fraction of free PSA. Osteoblastic metastases in bone may develop in later stages and appears as lower back pain and an increase in serum alkaline phosphatase and PSA. Undescended testis. Lack of spermatogenesis due to increased body temperature. Also associated with increased risk of germ cell tumors. Prematurity increases the risk of cryptorchidism. 95% of all testicular tumors. May present as a mixed germ cell tumor.

What tumors occur at each of these structures? How does prostatitis present? What are causes of acute prostatitis? What are causes of chronic prostatitis?

What is Benign Prostatic Hyperplasia (BPH)? How do you treat BPH?

What is Prostatic adenocarcinoma?

What is cryptorchidism? How common are testicular germ cell tumors?

What is a Seminoma?

Malignant, painless, homogenous testicular enlargement. Most common testicular tumor, mostly affecting males age 15-35. See large cells in lobules with watery cytoplasm and a fried egg appearance. These are radiosensitive, only metastasize late and have a great prognosis. Malignant, painful tumor with a worse prognosis than a seminoma. Often glandular or papillary morphology. Can differentiate and become other tumors and is associated with increased AFP and hCG. Yellow, mucinous tumor analagous to an ovarian yolk sac tumor. See Schiller Duval bodies which resemble primitive glomeruli. Malignant, hCG secreting tumor. Has distinct syncytiotrophoblastic and cytotrophoblastic elements. Causes hematogenous metastases. Similar to females except that mature teratomas in men are usually malignant. 5% of all testicular tumors, most of which are benign. Androgen producing tumor which causes gynecomastia in men, precocious puberty in boys. Contains Reinke crystals and is golden brown in color. Androblastoma from the sex cord stroma. Most common testicular cancer in older men. It's pretty much lymphoma in the testicles. A lesion in the serous covering of the testis. Presents as testicular masses that can be transilluminated. Dilated vein in pampinoform plexus which can result in infertility. Looks like a bag of worms. Increased fluid secondary to incomplete fusion of the processus vaginalis Dilated epididymal duct Gray, solitary, crusty plaque, usually on the shaft of the penis or on the scrotum. Peak incidence is in the 5th decade of life. Progresses to invasive squamous cell carcinoma in <10% of cases. Red, velvety plaques, usually involving the glans penis. Otherwise similar to Bowen's disease. Multiple papular lesions. Affects younger men but isn't usually invasive Essentially like any other SCC, just on the penis. Commonly associated with HPV and lack of circumcision. More common in Asia, Africa and South America. Bent penis due to acquired fibrous tissue formation. Glycogen and lipid accumulation, extra-cellular matrix changes, prolactin and IGF binding proteins increased, COX-2 increase which increases PGE2, and influx od dedidual NK cells. When the blastocyst enters the endometrial cavity, about 5 days after fertilization. Non-cellular, porous layer of glycoproteins around the oocyte. Early pregnancy factor, Platelet activating factor, human Chorionic Gonadotropin, Matrix Metalloproteinases and Inhibitors of Matrix Metalloproteinases, Heparin binding-EGF like growth factor receptors Apposition, Adhesion and Invasion Decidua that forms underneath the embryo Capsule of decidua over the embryo

What is an embryonal carcinoma? What is a yolk sac (endodermal sinus) tumor in a man? What is a Choriocarcinoma in a man? What is a teratoma in a man? How common are testicular non-germ cell tumors? What is a Leydig Cell Tumor? What is a Sertoli Cell Tumor? What is testicular lymphoma? What What What What is is is is a a a a tunica vaginalis lesion? Variocele? Hydrocele? spermatocele?

What is Bowen's Disease? Qhat is Erythroplasia of Queyrat? What is Bowenoid papulosis? What is Squamous Cell Carcinoma of the penis? What is Peyronie's Disease? What changes are seen in Decidualization? When does Blastocyst hatching occur? What is the Zona Pellucida? What proteins characterize preimplantation of the embryo? What are the three stages of implantation? What is the Decidua Basalis? What is the Decidua Capsularis?

What is the Decidua Paritalis? What happens to RBC and Plasma volume and mass in pregnancy? What happens to GFR and Creatinine Clearance during pregnancy? Why does respiratory alkalosis happen during pregnancy? Why do women get dyspnea during pregnancy?

Other decidua lining the uterine cavity Both are increased but plasma is increased more than RBC. This results in a dilutional effect in hematocrit. Creatinine clearance is increased. GFR increases fairly significantly. Increased clearance of creatinine and urea results in serum creatinine and urea that are really low. Thus normal creatinine and urea are problematic. Estrogen and progesterone both stimulate the respiratory center. Greater tidal volume and increased respiration rate also cause increased minute ventilation, thus more CO2 is blown off. Thus respiratory alkalosis from decreased PaCO2 May be due to decreased CO2 stimulating the respiratory center and causing subjective shortness of breath. hCG simulates TSH since they share the same alpha subunit. Thus it stimulates T4 secretion during the first 10 weeks. Estrogen promotes growth of the pituitary and the thyroid and synthesis of thyroid binding globulin. Thus T4 and cortisol are increased but free T4 and cortisol are the same. No menses for one year after age 40. Waxing and waning of estrogen levels from decreased ovarian function. Depletion of granulosa and thecal cells. Lack of response to gonadotropins. Increased LH stimulates androgen production in stromal cells (thus hirsutism) Surgical removal or radiation of ovaries. Turner syndrome. Family history of early menopause and left handedness (seriously???) Average age is 51. The age at which it's determined is genetically determined, but smokers reach menopause early and peri-menopause is mid-to late 40's. Secondary amenorrhea, hot flushes, night sweats, atrophic vaginitis with pruritis, burning, bleeding and dyspareunia. Also see mood swings, anxiety, depression, insomnia, decreased libido, urinary incontinence, headaches, tiredness, lethargy, and osteoporosis with increased risk of Colle's and vertebral fractures. Increase in LH and FSH from a drop in estrogen (LH) and progesterone (FSH) Estrogen replacement, progestins added if the uterus is still present to prevent endometrial adenocarcinoma. Thromboembolism, Coronary heart disease, stroke, slightly increased risk for breast cancer, increased risk for dementia in women over 65. Excess hair in normal hair-bearing areas. Hirsutism plus male secondary sex characteristics Increased muscle mass, acne, enlarged clitoris Both caused by increased androgens of either ovarian or adrenal origin. In the ovaries, the androgen is testosterone, in the adrenals it's DHEA-S

Why are Thyroxin and Cortisol increased in pregnancy? What defines menopause? What are the physiologic causes of menopause? What are non-physiologic causes of menopause? What is the average age of menopause and how is age at menopause determined?

What are some clinical findings in menopause? What are some labroratory findings in menopause? What are some treatment options for symptomatic menopause? What are risks of long term hormone replacement? What is Hirsutism? What is virilization? What are male secondary sex characteristics? What causes virilization or hirsutism?

What are some causes of virilization and hirsutism?

Polycystic ovary syndrome, idiopathic causes, adrenogenital syndrome, insuline resistance, drugs like androgenic progestins, phenytoin, cyclosporin, minoxidil. Can also be from ovarian tumors like a leydig or sertoli-leydig cell tumor, adrenal tumors producing Cushing syndrome, decreased steroid hormone binding globulin from obesity and hypothyroidism. Syndrome that occurs around menarche. See increased synthesis of LH and decreased synthesis of FSH. Increased LH increases androgen synthesis resulting most often in hirsutism. Androgens are then aromatized to estrogen in adipose cells increasing the risk of endometrial carcinoma. The increased estrogen feeds back positively on LH and negatively on FSH. Suppression of FSH causes follicle degeneration resulting in fluid accumulating and producing subcortical cysts that then enlarge the ovaries. Menstrual irregularities, mostly oligomenorrhea and often hirsutism, infertility or obesity. LH:FSH ratio >2. Increased serum testosterone and androstendione. Increased serum estrogen. Weight reduction in obese women. Low dose OCP's or medroxyprogesterone to suppress steroidogenesis and LH. Can use Spironolactone if OCP's are unacceptable to block androgen receptors on the hair follicle. LHreleasing hormone analogs inhibit ovarian androgen production. Loss of blood >80 mL per period. It's likely if sheets are stained despite heavy protection. Excessive passage of clots indicates that plasmin does not have enough time to dissolve clot. Painful menses, occuring in approximately 50% of women. Primary type occurs in ovulatory cycles due to increased prostaglandin PGF-2alpha. See increased uterine contractions from increased prostaglandins. The secondary type is from endometriosis, adenomyosis, leiomyomas, or cervical stenosis. NSAID's, OCP, nifedipine, magnesium sulfate Essentially deal with the underlying disease. Abnormal uterine bleeding that is unrelated to an anatomic cause. Note that this is a diagnosis of exclusion. Menorrhagia, Hypomenorrhea, Metrorrhagia, Menometrorrhagia, Oligomenorrhea, Polymenorrhea Anovulatory cycle in 90% of cases but less than 10% due to anovulation during reproductive years. Excessive estrogen stimulation relative to progesterone resulting in an absent secretory phase. It produces excessive endometrial hyperplasia and excessive bleeding. Inadequate luteal phase resulting in inadequate maturation of the corpus luteum. This causes inadequate synthesis of progesterone and delay in the development of the secretory phase. May see decreased 17-OH progesterone . If the follicle size is normal, supplement progesterone. If the follicle size is inadequate, give clomiphene sulfate.

What is Polycystic Ovarian Syndrome? What are clinical findings in polycystic ovarian syndrome? What are some lab findings in PCOS?

What is the treatment in PCOS? What is Menorrhagia?

What is Dysmenorrhea? What is the treatment for Primary Dysmenorrhea? What is the treatment for secondart Dysmenorrhea? What is dysfunctional uterine bleeding? What are some types of dysfunctional uterine bleeding? What is most common cause of irregular bleeding? What causes anovulatory dysfunctional uterine bleeding? What causes ovulatory dysfunctional uterine bleeding? How do you treat ovulatory dysfunctional uterine bleeding?

What is Primary Amenorrhea? What is Secondary Amenorrhea? What are some causes of amenorrhea? What are causes of abnormal vaginal bleeding in a pre-pubertal girl? What are some causes of abnormal vaginal bleeding between menarche and 20 years? What are some causes of abnormal vaginal bleeding between ages 2040? What are some causes of abnormal vaginal bleeding after age 40? What part of the placenta covers the fetal surface? What covers the chorion? What covers the maternal surface of the placenta? Where do the chorionic villi project? What does the intervillous space contain? What lines the chorionic villi? What forms the outside layer of the trophoblast? What does the Syncytiotrophoblast do? What forms the inside layer of the trophoblast? How many vessels are contained in the umbillical cord? What risks are related to a single umbillical artery? What causes most placental infections?

Absence of menses by age 16. Most cases are due to constitutional delay with a family history of delayed menses. Absence of menses for 3 months, most commonly due t pregnancy. Hypothalamic or pituitary dysfunction resulting in decreased LH and FSH which results in decreased estrogen and progesterone. Ovarian disorders cause problems in synthesis of estrogen or progesterone. Vulvovaginitis, poor hygeine, infection, gonrrhea, sexual abuse, foreign bodies, embryonal rhabdomyosarcoma

Anovulatory dysfunctional uterine bleeding, Von Willebrand's disease Pregnancy and related complications, ovulatory dysfunctional uterine bleeding, PID, hypothyroidism, submucosal leiomyomas, adenomyosis, endometrial polyp, endometriosis

Anovulatory dysfunctional uterine bleeding, endometrial hyperplasia, cancer. Entirely covered by the chorionic plate. The chorionic villi vessels converge with the umbillical cord. Chorion is covered with amnion Contains cotyledons covered by decidua basalis. Into the intervillous space Maternal blood that delivers oxygen and nutrients and spiral arteries from the uterus that empty into the space Trophoblastic tissue Syncytiotrophoblast. Synthesizes hCG, and HPL which directly correlates with placental mass and has anti-insulin activity. Cytotrophoblastic tissue One umbillical vein and two umbillical arteries. The vein carries the oxygenated blood in this case Increased incidence of congenital anomalies, defects including cardiovascular defects, trisomy 18 and esophageal atresia. Ascending infections, often from premature rupture of membranes

How should you treat a placental infection even if culture is negative? What is Funisitis? What is Placentitis? What is chorioamnionitis? What complications might arise from chorioamnionitis? What is Placenta Previa? How does Placenta Previa present? How do you diagnose Placenta Previa? What is Abruptio Placentae? What are risks for abruptio placentae? What are the clinical signs of abruptio placentae? What is Placenta Acreta?

Treat prophylactically with IV Ampicillin+Erythromycin followed by PO amoxicillin and erythromycin. If culture positive you can give IV penicillin or ampicillin Infection of the umbillical cord Infection of the placenta Infection of the fetal membranes Neonatal sepsis and meningitis. Treat with Cefoxitin or Ticaricillin-Clavulanate Implantation over cervical os. Previous C Section is major risk factor Painless vaginal bleeding, usually second or third trimester. The uterus is soft and non-tender and fetal distress is usually not present. Do not do a pelvic exam. Transabdominal ultrasound localizes the placenta and transvaginal ultrasound confirms placenta previa. Premature separation of the placenta due to formation of a retroplacental clot. This separates the placenta from the implantation site. This is most common cause of late pregnancy bleeding Hypertension, smoking, cocaine, advanced maternal age, trauma, chorioamnionitis, premature membrane rupture, previous abruptio placentae. Painful uterine bleeding, forceful uterine contractions or signs of preterm labor, usually see evidence of fetal distress Direct implantation into muscle without intervening decidua. Causes great risk for hemorrhage during delivery, commonly requiring surgery to control bleeding. Often requires hysterectomy. Umbilical cord inserts away from the placental edge-the vessels pass to the placenta through the membranes between the amnion and chorion. Causes increased risk for hemorrhage if the vessels are torn. Deliver by C Section to avoid vessel tear. Increased risk of hemorrhage if they are detached. Diabetes mellitus, Rh hemolytic disease of the newborn, congenital syphilis Monochorionic and monoamniotic although they can have dichorionic placentas

What is Velamentous insertion? What risks do accessory lobes of the placenta pose? What can cause an enlarged placenta? What type of placentas do Monozygotic twins have? What risks are associated with monochorionic, diamnionic placentas? What is Preeclampsia? What are risk factors for Preeclampsia? What is the pathogenesis of Preeclampsia?

Twin Twin Transfusion syndrome. Toxemia of pregnancy First pregnancy, more common in women <20 years and >35 years, history of previous preeclampsia, positive family history, multiple gestations, african american, thrombocytosis, obesity Abnormal placentation causing mechanical or functional obstruction of the spiral arteries. The abnormal trophoblastic tissue invades the spiral arteries. Imbalance favors vasoconstriction over vasodilation (decreased PGE2 and NO, increased TXA2, Ang II and increased sensitivity to Ang II)

What are pathologic findings in PreEclampsia? What are clinical findings in PreEclampsia? What are some other symptoms in Pre-Eclampsia? What is a Hyaditiform Mole?

What is a complete Hyaditiform Mole? Which type of Mole has an increased risk of Choriocarcinoma?

What is a partial Hyaditiform Mole? What is a Choriocarcinoma? Where does Choriocarcinoma metastasize? What is the composition of amniotic fluid? What is the quantity of amniotic flud maintained? What is Polyhydramnios? What is Oligohydramnios? What can Alpha Fetoprotein indicate in pregnancy? What does the Lecithin to Sphingomyelin ratio indicate? What can increase surfactant production in the fetus? Where is estriol made in pregnancy? What part of estriol synthesis does the fetal adrenal cortex control?

Premature aging of the placenta, multiple placental infarctions, spiral arteries show atherosclerosis Hypertension, proteinuria from leaky capillaries (increased inflammation), dependent pitting edema from loss of albumin, weight gain, seizures in eclampsia, swollen endothelial cells in glomerular capillaries producing oliguria. Right upper quadrant pain and hepatomegaly, periportal necrosis with increased transaminases, HELLP syndrome Benign tumor of the chorionic villus from an empty egg and 2 sperm or an egg and 2 sperm. The entire placenta is neoplastic. Dilated swollen villi without fetal blood vessels. No embryo is present. Ovum 46, XX, lacking maternal chromosomes. The chromosomesare derived from the father, either 2 sperm or duplicated 23X sperm in the ovum Complete mole. Presents with painless vaginal bleeding in fourth, fifth month of pregnancy. Causes severe vomiting, pre-eclampsia, uterus that is too large for gestational age, increased hCG for gestational age, and snowstorm appearance on ultrasound. Not all villi are neoplastic or dilated? Embryo is present but this is triploid. Egg with 23X is fertilized by 23X and 23Y sperm. (Not that if the embryo is doubled, it's not considered a mole). This has a low risk of choriocarcinoma. malignant tumor composed of syncytiotrophoblast and cytotrophoblast without chorionic villi. Risks are complete mole, spontaneous abortion and normal pregnancy Lungs and vagina-hemorrhagic lesions Predominantly fetal urine, initially plasma ultra-filtrate from mom. High salt content causes ferning when dried on a slide-good sign of premature rupture of amniotic sac. Swallowed and recycled by the fetus. Excessive amniotic fluid. Causes are tracheoesophageal fistula, duodenal atresia, maternal diabetesmaternal hyperglycemia causes fetal hyperglycemia resulting in fetal polyuria. Decreased amount of amniotic fluid. Caused by juvenile polycystic kidney disease, fetal genitourinary obstruction, uteroplacental insufficiency and premature rupture of membranes. Increased maternal AFP indicates open neural tube defects (often related to Folate deficiency). Decreased maternal AFP can indicate Down syndrome. Lecithin is synthesized by type II Pneumocytes which decreases alveolar tension to prevent atelectasis. L:S ratio >2 indicates adequate surfactant. Cortisol and thryroxine increase surfactant synthesis. Maternal administration of glucocorticoids can increase surfactant if the baby must be delivered before term. Insulin inhibits surfactant synthesis. Derived from fetal adrenal gland (DHEA-S) which is aromatized by the placenta.

Fetal adrenal cortex converts pregnenolone from the placenta to DHEA-S.

What does the fetal liver do in estriol synthesis? What does the maternal placenta do in estriol synthesis? What does the maternal liver do to estriol? What does decreased estriol indicate? What is the triad of markers in Down syndrome? What is the most high density location of breast tissue? What effects do sex hormones have on the breast during the menstrual cycle? What hormones affect lactation? Where do outer quadrant breast cancers drain? Where do inner quadrant breast cancers drain? What are normal causes of Galactorrhea? What are pathologic causes of Galactorrhea? What causes Bloody nipple discharge? What causes prululent nipple discharge? What causes Green-Brown nipple discharge? What is the most common cause of Breast Pain? What is Mondor's disease?

Hydroxylates DHEA-S to 16-OH-DHEA-S Initially converts LDL to pregnenolone for fetal processing. Placental sulfatase then cleaves off the sulfate from 16-OH-DHEA-S and converts it to free unbound estriol via aromatase. Conjugates it to estriol sulfate and estriol glucosiduronate which is then excreted in the maternal urine and bile. Sign of fetal-maternal-placental dysfunction Decreased urine estriol, decreased AFP, increased serum Beta-hCG Upper outer quadrant-thus cancer is most commonly located in this location. Also underneath the nipple.

Estrogen stimulates ductal and alveolar growth. Progesterone stimulates alveolar differentiation. Prolactin-stimulates and maintains lactogenesis. Oxytocin-released by the suckling reflex which causes expulsion of milk into the ducts. Axillary lymph nodes Internal mammary lymph nodes. Mechanical stimulation of the nipple from prolonged suckling or sexual intercourse. Prolactinoma, primary hypothyroidism (decreased T4 causes increased TRH which stimulates PRL), drugs like OCP's, phenothiazines, methyldopa, H2-Receptor blockers and angiolytics. Intraductal papilloma, ductal cancer Acute mastitis due to Staph A., usually related to breast feeding Mammary duct ectasia (plasma cell mastitis) Fibrocystic change Superficial thromboplebitis of veins overlying the breast, presenting as a palpable, painful cord. Most common painful breast mass in women <50 years old. Causes distortion of normal cyclic breast changes. Some cysts have hemorrhage into the cyst fluid-called blue-domed cysts. Vary in size with the menstrual cycle but have no malignant potential Proliferation of small ductules/acini in the lobule-pattern is often confused with infiltrating ductal cancer. Often contains microcalcifications.

What is Fibrocystic change? What is sclerosing adenosis?

What is Ductal Hyperplasia? What is Mammary duct ectasia/plasma cell mastitis?

Ducts are estrogen sensitive. See papillary proliferation called papillomatosis, apocrine metaplasia (change to sweat producing glands), and atypical ductal hyperplasia (increased risk for carcinoma) Main ducts fill up with debris causing dilation, rupture and inflammation. Results in greenish-brown nipple discharge. May result in skin and nipple retraction stiulating cancer but no increased risk for breast cancer. Trauma to breast tissue. Microscopic findings are lipid-laden macrophages with foreign body giant cells, fibrosis and dystrophic calcification. See a painless indurated mass which is painful in the acute stage and may produce skin retraction stimulating cancer. Most common breast tumor in women <35 years. Discrete movable, painless or painful mass. It's a benign tumor derived from the stroma which proliferates and compresses the ducts. The duct epithelium is not neoplastic. Estrogen sensitive so increases in size during pregnancy. May spontaneously involute during menopause. Bulky tumor derived from stromal cells. Most commonly benign but can be malignant in some cases-see hypercellular stroma with signs of mitoses in malignancy. Lobulated tumor with cystic spaces containing leaflike extensions. Most common cause of bloody nipple discharge in women <50. Develops in the lactiferous ducts or sinuses. No increased risk for cancer. Prolonged estrogen stimulation, genetic susceptibility, especially if first generation relatives. Prolonged estrogen stimulation from either early menarche or late menopause or nulliparity. BRCA 1 and BRCA 2, Li-Fraumeni, RAS oncogene, ERBB2, RB suppressor gene Breast feeding, moderate or vigorous physical training, healthy body weight. Painless mass in the breast, usually the upper outer quadrant. Skin or nipple retraction, painless axillary lymphadenopathy, hepatomegaly and bone pain if there are metastases. Mammography-detects 80-90% of non-palpable breast masses. Does not distinguish benign from malignant lesions. Can identify microcalcifications and spiculated masses with or without microcalcification. Ductal carcinoma in situ, and sclerosing adenosis. Five or more microcalcifications that are punctate, microlinear or branching all suggest malignancy

What is traumatic fat necrosis?

What is a Fibroadenoma of the breast?

What is a Phyllodes tumor? What is an Intraductal Papilloma? What are risk factors for breast cancer? What are some genetic markers for breast cancer? What decreases risk for breast cancer? What are clinical findings in breast cancer? What is the primary screening test for breast cancer? Where do microcalcifications most commonly occur? How is estrogen and progesterone receptor expression related to prognosis? What is a Ductal Carcinom in Situ (DCIS)? What is a Lobular Carcinoma in Situ (LCIS)?

ER/PR expression generally confers a good prognosis whereas ERB2/NEU has a poor prognosis if amplified. Nonpalpable mass. Forms a cribiform pattern (seive like) or comodo like pattern (necrotic center). Commonly contains microcalcifications which allow it to be detected on mammogram. Nonpalpable mass. Virtually always an incidental finding on breast biopsy for something else. Not identifiable on mammography. Lobules are distended with bland neoplastic cells. Usually ER/PR positive. Increased incidence of cancer in the opposite breast, that isn't LCIS.

What is Infiltrating Ductal Carcinoma? What is Paget's disease? What is Medullary Carcinoma of the breast? What is inflammatory carcinoma of the breast? What is Invasive Lobular Carcinoma? What is Tubular Carcinoma? What is a Colloid (Mucinous) Carcinoma?

Malignant, invasive breast tumor. Has a stellate morphology. Indurated, gray-white tumor. 1/3 have ERB2 amplification conferring poor prognosis. These look gritty on cut section and have reactive desmoplasia causing induration. Extension of DCIS into the lactiferrous ducts and skin of the nipple producing a rash with or without nipple retraction. Palpable mass often present, see Paget's cells as well. Invasive tumor associated with BRCA1 mutations. Bluky, soft tumor with large cells and a lymphoid infiltrate. Most are ER/PR negative. Invasive tumor that presents with erythematous breast with dimpling of the skin like an orange peel from fixed opening of the sweat glands. Plugs of tumor block the lumen of dermal lymphatics causing localized lymphedema. Has a very poor prognosis. Invasive mass of neoplastic cells arranged in a linear fashion or in concentric circles. Invasive mass that develops in terminal ductules. Increased incidence of cancer in the opposite breast. Invasive mass that usually occurs in older women. Neoplastic cells surrounded by extracellular mucin. Benign glandular proliferation in the male breast due to estrogen from increased enstrogens, decreased androgens or a defect in androgen receptors. Most often unilateral. Normal in newborns, puberty or the elderly. Cirrhosis causes an inability to metabolize estrogen or to metabolize 17-ketosteroids which are then aromatized to estrone. Genetic diseases like Klinefelter's and testicular feminization cuase gynecomastia. Drugs that displace estrogen from SHBG, such as spironolactone or ketoconazole or drugs with estrogen activity like DES or digoxin, or androgen blocking drugs like spironolactone or flutamide or that decrease androgen production like leuprolide. These all increase estrogen. Infection with Neisseria Gonorrhea Thinning of the epidermis with parchment appearing skin. Most commonly in post-menopausal women. White plaque like skin lesion (leukoplakia) due to squamous cell hyperplasia. Small risk for developing Squamous Cell Carcinoma. Benign tumor of the apocrine sweat gland. Causes painful nodule on the labia majora. Dysplasia of the vulva, ranging from mild to carcinoma in situ. Strong association with HPV 16 and high risk of developing squamous cell carcinoma

What is Gynecomastia?

What causes pathologic gynecomastia? What is the most common cause of Bartholin gland abscesses? What is Lichen Sclerosis? What is Lichen Simplex Chronicus? What is a Papillary Hidradenoma? What is Vulvar Intraepithelial Neoplasia? What are risk factors for squamous cell carcinoma of the vulva? What is extramammary Paget's disease? What is Malignant melanoma of the vulva?

HPV 16, smoking, immunodeficiency. Red, crusted vulvar lesion. Intraepithelial adenocarcinoma derived from primitive epithelial progenitor cells. Malignant Paget cells contain mucin which is Periodic Acid Schiff positive. Spreads along the epithelium but rarely invades the dermis. Melanoma cells, histologically similar to Paget cells except these are PAS negative.

What type of lesion results from infection with Calymmatobacterium Granulomatis? What types of lesions result from infection with Candida Albicans?

Gram negative coccobacilli that causes granuloma inguinale. It's phagocytosed by macrophages forming Donovan bodies and results in creeping, raised sores that heal by scarring. Treat with bactrim or doxy. Yeast and pseudohyphae which should be part of the normal vaginal flora. Causes vaginitis, pruritic vaginitis with a white discharge and fiery red mucosa. Risk factors are diabetes, antibiotics, pregnancy and OCP's STD-commonly coinfecting with Neisseria Gonorrhea. See red inclusions (reticulate bodies) in squamous cells which then divide and form elementary bodies which can reinfect other cells. Causes sterile pyuria, epididdmitis, proctitis (in males obviously) and urethritis, cervicitis, PID, perihepatitis (Fitz-Hugh Curtis), proctitis and bartholin gland abscesses (in females obviously). Can also cause conjunctivitis and pneumonia in a newborn. Lymphogranuloma venerum, papules with no ulceration, inguinal lymphadenitis with granulomatous microabscesses and draining sinuses. Lymphedema of the scrotum or vulva and possibly rectal strictures in women Gram negative rod that causes bacterial vaginosis. Most common vaginitis which presents with malodorous discharge. Organisms adhere to the squamous epithelium forming clue cells. Gram negative rod that causes Chancroid. Male dominant disease, often correlated with HIV. Causes painful genital warts and perianal ulcers with suppurative inguinal nodes which main have draining sinuses. STD with the virus remaining latent in the sensory ganglia. Causes recurrent vesicles that ulcerate on the vulva, penis, cervix and perianal area. See multinucleated squamous cells on Tzanck prep Types 6 and 11 associated with Condyloma Acuminata (warts)-fernlike or flat lesions in the genital area. Types 16 and 18 associated with dysplasia and squamous cell carcinoma. See koilocytes in squamous epithelium. Cells have wrinkled, pyknotic nuclei surrounded by a clear halo. Vaccine! Topical podophyllin, alpha-IFN injections and imiquimod cream Gram negative diplococcus that infects glandular transitional epithelium in sites similar to Chalmydia. Causes prululent lesions and urethritis. Can cause ectopic pregnancy, male sterility, disseminated gonococcemia, septic arthritis, and Fitz Hugh Curtis. Septic arthritis in the knee, tenosynovitis of the hands and feet, pustules on the hands and feet Gram negative spirochete that causes syphillis. Primary syphillis presents with a solitary, painless, indurated chancre on the penis, labia or mouth. Secondary presents with a maculopapular rash on the trunk, palms and soles along with generalized lymphadenopathy, condylomata lata (flat lesions) and alopecia. Tertiary syphillis presents with neurosyphillis, aortitis and gummas. RPR or VDRL. Titers should decrease after treatment.

What type of lesion results form infection with Chlamydia Trachomatis? What types of lesions result from infection with Chlamydia Trachomatis subspecies? What types of lesions are seen with infection by Gardnerella Vaginalis? What types of lesions result from infection with Hemophilus Ducreyi? What types of lesions result from infection with HSV-2?

What types of lesions result from infection with HPV? How do you treat HPV? What types of lesions result from infection with Neisseria Gonorrhoeae? What are signs of disseminated Gonococcemia?

What types of lesions result from infection with Treponema Pallidum? What are the non-specific screening tests for Syphillis?

What are the confirmatory tests for Syphillis? What is the Jarisch-Herxheimer reaction? what types of lesion results from infection with Trichamonas Vaginalis? What is Rokitansky-Kuster Hauser Syndrome? What is a Gartner's Duct cyst? What is a Rhabdomyoma? What is an Embryonal Rhabdomyosarcoma? What is clear cell adenocarcinoma of the vagina? What is Vaginal Adenosis? What are some other DES related abnormalities? What is vaginal squamous cell carcinoma? What does the cervix actually consist of? What lines the exocervix? What lines endocervical glands? How does the endocervical epithelium transform into the exocervical epithelium? What is the pathogenesis of a Nabothian cyst? What is acute cervicitis? What are clinical findings in acute cervicitis? What causes chronic cervicitis? What is follicular cervicitis? What is the purpose of a Cervical Pap test?

FTA-ABS which is positive with or without treatment Intensification of rash in primary or secondary syphillis after proteins are released from the dead organisms following penicillin treatment Flagellated protozoan with jerky motility which produces vaginitis, cervicitis and urethritis. Causes a strawberry colored cervix and fiery red vaginal mucosa with greenish, frothy discahrge. Absence of the upper vagina and uterus resulting in primary amenorrhea Remnant of the Wolffian/mesonephric duct which presents as a cyst on the lateral wall of the vagina. Benign tumor of skeletal muscle in the vagina (can also be on the tongue or heart) Necrotic, grape like mass protruding from the vagina, most often in girls <5 years Adenocarcinoma of the vaginal wall (pretty self explanatory). Occurs in women with DES exposure since DES inhibits mullerian differentiation-tubes, uterus, cervix and upper third of the vagina Precursor lesion for squamous cell carcinoma. Produces red, superficial ulcerations in the upper portion of the vagina Abnormally shaped uterus that thwarts implantation (T shape). Cervical incompetence which can cause recurrent miscarriage. It's what it sounds like. That said, primary SCC is associated with HPV 16. Most of these are actually extensions of cervical SCC into the vagina. Endocervix and exocervix. The exocervix begins at the cervical os squamous epithelium Mucus secreting columnar cells Endocervical epithelium migrates down to the exocervix where exposure to the acid pH of the vagina causes squamous metaplasia. This area is called the transformation zone and is the most likely location for squamous dysplasia and cancer. Metaplastic squamous cells block endocervical gland orifices resulting in obstruction to outflow of mucus. This is a normal finding however. Acute inflammation is often present in the transformation zone, however pathologic acute inflammation may be due to infection-Chlamydia, Neisseria, Trichomonas, Candida, HSV, HPV. Vaginal discharge, pelvic pain, dyspareunia, pain on palpation (chandelier sign), easy bleeding and erythematous or exudative cervical os. Essentially persistence of acute cervicitis Pronounced lymphoid infiltrate with germinal centers caused by Chlamydia Trachomatis. Screening test for squamous dysplasia and cancer. Evaluate the hormone status of the patient.

What do superficial squamous cells indicate on Pap? What do intermediate squamous cells on Pap indicate? What do parabasal cells on Pap indicate? What types of cells are seen on Pap from a non-pregnant and pregnant woman? What is a Cervical Polyp? Describe Cervical Intraepithelial Neoplasia, CIN What is CIN I? What is CIN II? What is CIN III? What is the epidemiology of cervical cancer? What are clinical findings in cervical cancer? What are some characteristics of cervical cancer? What is the sequence to menarche? When does ovulation occur? What mediates the secretory phase of the cycle?

Adequate estrogen Adequate progesterone Lack of estrogen and progesterone. Non-pregnant: 70% superficial, 30% intermediate squamous cells. Pregnant: 100% intermediate squamous cells from progesterone effect. Non-neoplastic polyp that protrudes from the cervical os. Arises from the endocervix, most commonly in perimenopausal or multigravida women. Most cases associated with HPV which produces koilocytes in squamous cells. Associated with early age of sexual intercourse, multipe high-risk partners, high risk HPV types, smoking, OCP's and immunodeficiency. Mild dysplasia involving the lower third of the epithelium Moderate dysplasia involving the lower 2/3 of the epithelium Severe dysplasia to carcinoma in situ involving the full thickness of the epithelium Least common GYN cancer with higher incidence in developing countries. Most are squamous cell carcinomas with the same risk factors as CIN Abnormal vaginal bleeding, often post coital, malodorous discharge Cancer often extends down into the vagna and out into the lateral wall of the cervix and vagina. May infiltrate the bladder wall and obstruct the uterus causing postrenal azotemia and possibly death. May metastasize distantly, e.g. to the lungs. Breast budding (Thelarche), growth spurt, pubic hair, axillary hair, menarche (mean age is 12.8 years). Between days 14 and 16 Progesterone Fertilization usually occurs in the ampullary portion of the Fallopian tube. The fertilized egg spends 3 days there, 2 days in the uterine cavity and then implants in the endometrial mucosa on day 21. There is an exaggerated secretory phase in pregnancy called the Arias-Stella phenomenon. Drop-off in serum estrogen and progesterone signalling endometrial cells to undergo apoptosis. Prepares the follicle of the month, increases aromatase synthesis in the granulosa cells, increased synthesis of LH receptors. Increases synthesis of 17-ketosteroids in the theca interna (DHEA and androstenedione). Convert DHEA to androstenedione and androstenedione to testosterone. Increase aromatization of testosterone. (Obviously LH isn't doing these things directly but it uprgulates necessary enzymes)

What changes occur after fertilization? What initiates menses? What are the functions of FSH?

What are the functions of LH?

What hormonal changes are seen in pregnancy? What is in Oral Contraceptive Pills and how do they work? Where does Estradiol come from? Where does Estrone come from? Where does Estriol come from? Where does androstendione come from in a woman? Where does DHEA come from in a woman? Where does testosterone come from in a woman? What is Sex Hormone Binding Globulin? What does SHBG have a greater affinity for?

Human chorionic gonadotropin-synthesized in the syncytiotrophoblast lining the chorionic villus. hCG acts as an LH analog and maintains the corpus luteum to produce progesterone. Mixture of estrogens and progestins which then prevent the midcycle LH surge and ovulation. Progestin arrests the proliferative phase and cause gland atrophy and also inhibit LH directly. OCP's also render the cervical mucus hostile to sperm and alter Fallopian tube motility. Aromatized testosterone in granulosa cells. Primary estrogen in non-pregnant women. Weak estrogen produced during menopause from adipose cell aromatization of androstendione End product of estradiol metabolism. Primary estrogen of pregnancy derived from fetal adrenal, placenta and maternal liver. Equal derivation from ovaries and adrenal cortex Almost exclusively from the adrenal cortex derived from conversion of androstenedione to testosterone in the ovaries and adrenal glands. Can be converted to DHT peripherally. Binding protein for both estrogen and testosterone, mostly synthesized in the liver. Androgens, obesity and hypothyroidism all decrease SHBG SHBG preferentially binds testosterone over estrogen thus lack of SHBG can cause hirsutism in women. Acute inflammation of the endometrium, most commonly as a result of bacterial infection following delivery or miscarriage. Group B strep, staph a, bacteroides, C. trachomatis, N. Gonorrhoeae, E Coli. Fever, uterine tenderness, prululent or foul vaginal discharge and abdominal pain. Retained placenta, gonorrhea, IUD (with infection) Like all chronic inflammatory conditions, you see plasma cells Invagination of the stratum basalis into the myometrium. See glands and stroma thickening in the myometrium and general enlargement of the uterus. Menorrhagia, dysmenorrhea or pelvic pain Functioning endometrial glands and stroma located outside the uterus causing cyclic bleeding of gland and stromal implants. Essentially reverse menses through the Fallopian tube allows inplantation of viable endometrial cells. Can also be from vascular spread. Most common sites are ovaries, rectal pouch, Fallopian tubes and intestines. Dysmenorrhea, abnormal bleeding, painful stooling during menses, intestinal obstruction and bleeding during menses, increased risk for ectopic pregnancy and enlargement of the ovaries with blood filled cysts Benign polyp on the endometrium that enlarges with estrogen stimulation. Does not progress to endometrial carcinoma but it can protrude through the cervix into the vagina.

What is acute endometritis? What are clinical findings in acute endometritis? What causes chronic endometritis? What is the key histologic finding in chronic endometritis? What is Adenomyosis? What are clinical findings in adenomyosis?

What is Endometriosis? What are clinical findings in Endometriosis? What is an endometrial polyp?

What are clinical findings of an endometrial polyp? What is a Hyatid Cyst of Morgagni?

Common cause of menorrhagia, spotting in between periods or after menopause Cystic mullerian remnant most often in the fibriated end of the tube. May undergo torsion causing pain. Inflammation in the pelvis, often due to N. Gonorrhoeae or C. Trachomatis. See Fallopian tubes that are filled with pus or see hydrosalpinx (clear fluid in Fallopian tube). Causes fever, lower abdominal pain, cervical motion tenderness, abnormal uterine bleeding, vaginal discharge, mucopurulent discharge in the cervical os, and right upper quadrant pain (FHC Syndrome) Multiple sex partners, vaginal douching, prior PID, unprotected sex Invagination of the mucosa of the tube into muscle (tubal diverticulosis). Produces nodules in the tube that narrow the lumen. Most likely a result of infection and can result in infertility and ectopic pregnancy. Pregnancy that isn't in the uterus. Most often in the Fallopian tubes. Suspect with increased hCG and sudden lower abdominal pain. Confirm with ultrasound. May be clinically mistaken for appendicitis. Scarring from previous PID, Endometriosis, Altered tubal motility (SIN), progestin only pill, previous tubal ligation, prior abdominal surgery.

What is pelvic inflammatory disease? What are some risk factors for PID? What is Salpingitis Isthmica Nodosa (SIN)?

What is ectopic pregnancy? What are risk factors for ectopic pregnancy? Where in the tubes do ectopic pregnancies most commonly implant? What are some clinical findings in ectopic pregnancy? How do you diagnose ectopic pregnancy? What is Oophoritis?

Most occur in the broad ampullary region below the fimbriae. Sudden onset of lower abdominal pain and tenderness, usually about 6 weeks after LMP, adnexal tenderness, peritoneal signs, abnormal uterine bleeding, hypovolemic shock as a result of intraperitoneal hemorrhage. Beta hCG is a good screening test but a positive hCG doesn't mean that there is an ectopic pregnancy. Vaginal ultrasound showing an amniotic sac is confirmatory. Inflammation of the ovary, possible as a result of mumps or PID. Bilateral ovarian enlargement from hypercellular ovarian stroma. Stroma have vacuolated (leutenized) stromal hilar cells which synthesize excess androgens. May cause hirsutism or virilization. Associated with obesity, acanthosis nigracans, insulin resistance, and hypertension. Nulliparity-increased number of ovulatory cycles increases risk, also causes increased risk for surface-derived ovarian tumors. Genetic factors are BRCA1 and BRCA2 suppressor gene mutations, Lynch syndrome, Turner syndrome (dysgerminoma), Peutz-Jeghers syndrome (sex cord tumors with annular tubules), history of breast cancer, postmenopausal estrogen replacement, obesity cancers are similar to those seen in the testicle, not many are malignant. Sex cord stromal tumors-derive from stromal cells, may be hormone producing, most are benign. Metastases-most commonly from breast, and stomach (Krukenberg tumors)

What is stromal hyperthecosis?

What are risk factors for Ovarian cancer? How can ovarian tumors be classified?

What are some clinical findings in Ovarian tumors? What is a common tumor marker of malignant ovarian tumors?

Abdominal enlargement from fluid. Malignant ascites may cause induration in the rectal pouch on digital rectal exam and intestinal obstruction with colicky pain. Palpable ovarian mass in postmenopausal woman, malignant pleural effusion, torsion and infarction (cystic teratomas), signs of hyperestrinism in estrogen secreting tumors or virilization in androgen secreting tumors. Increased CA-125- only in surface derived tumors Most common group of primary benign and malignant tumors, many are bilateral. Cysts are lined by ciliated cells (like Fallopian tubes). A Serous Cystadenoma is benign. A Serous Cystadenocarcinoma is malignant and has psammoma bodies and dystrophic calcification. Cysts lined by mucus-secreting cells (like endocervical cells). Cause large multi-nucleated tumors. Seeding of tumor produces pseudomyxoma peritonei. A mucinous cystadenoma is benign and may be associated with Brenner tumors. A mucinous cystadenocarcinoma is malignant. Malignant tumor associated with endometrial carcinoma. Commonly bilateral Usually a benign tumor that contains Walthard's rests (traditional-like epithelium) Most common benign germ cell tumor. See ectodermal differentiation (hair, sebaceous glands, teeth) mostly found in a nipple like structure called Rokitansky Tubercle. A Struma Ovarii subtype has functioning thyroid tissue Benign tumor associated with Meigs' syndrome (ascited, right sided pleural effusions). Commonly calcify. Low grade malignant tumor which produces estrogen and contains Call-Exner bodies Benign tumor that produces androgens. Pure leydig cell tumors contain cells with crystals of Reinke. Malignant tumor with a mixture of germ cells (dysgerminoma) and sex-cord stromal cells. Associated with abnormal sexual development. May calcify Metastasis to the ovary. Contains signet ring cells from hematogenous spread of gastric cancer.

What is a Serous Ovarian tumor?

What is a Mucinous tumor of the ovary? What is an endometroid tumor? What is a Brenner tumor?

What is a cystic teratoma? What is a Thecoma-Fibroma? What is a Granulosa-Theca cell tumor? What is a Sertoli-Leydig cell tumor? What is a Gonadoblastoma? What is a Krukenberg tumor?

Renal
What does the urinary system derive from? How many sets of kidneys are there? What is the pronephros? Intermediate mesoderm of the posterior wall of the abdominal cavity. Three sets of kidneys-pronephros, mesonephros and metanephros First kidney. Nonfunctional and disappears by week 4 Forms after the pronephros and forms the mesonephric/Wolffian duct. That eventually connects the mesonephros to the cloaca and forms adult genital structures. Forms the definitive kidney Primary ureteric bud. Becomes the glomerulus, Bowman's capsule, Loop of Henle, Distal Collecting tubule and collecting system Outgrowth of the Mesonephric duct which joins the metanephros to form the ureteric bud. Forms the major and minor calyces, renal pelvis and ureters. Allantois goes to Urachus and becomes the Median umbilical ligament. Don't confuse this with the medial umbilical ligament which is a remnant of the umbilical artery. Malformation of the Ureteric Bud which results in bilateral renal agenesis. Results in oligohydramnios/Potter's syndrome Clubfoot, flipper hands, hyperextensible joints, and compressed thorax Sloping forehead, flattened nose, recessed chin, low floppy ears. Results from compression of the fetus against the wall of the the amniotic sac. Fetal lungs mature through swallowing of amnion which allows the lungs to expand. Thus decreased amnion causes decreased expansion of the lungs.

What is the mesonephros? What is the metanephros? What is the excretory system of the kidneys derived from? What are the collecting ducts of the kidney derived from?

What adult structure does the Allantois become?

What is Potter's Sequence? What are the limb deformities in Potter's Syndrome? What are the facial deformities in Potter's Syndrome? Why does Pulmonary Hypoplasia result from Potter's Syndrome? What can occur if the allantois fails to obliterate? What does the urogenital sinus become?

Patent Urachus results in Urachal fistula at birth Urinary bladder and urethra

Wat causes a pelvic kidney? How do pelvic kidneys present?

During development, the embryologic kidneys must ascend and pass under the umbilical arteries. If a kidney can't pass, it remains in the pelvis Obstructive hydronephrosis and vesicoureteric reflux. May have pain or infection. Kidneys are pushed close together while ascending under the umbilical arteries. Causes the lower poles to fuse which causes it to look like a horseshoe and get trapped underneath the inferior mesenteric artery. Associated with Turner's Most are asymptomatic but can present with UTI followed by obstructive hematuria or abdominal pain. Predisposes to nephrolithiasis IV pyelogram shows rotated calyces but doesn't show the isthmus. Need a Dimercaptosuccinic Acid Scan (DMSA) Origin-vertebral column (T12-L5), insertion-lesser trochanter of the femur. Innervation-Ventral rami of L1-3. Blood supplymucular branches of the medial femoral and circumflex artery. Actions-flex thigh and trunk and laterally rotate the hip. Origin-Vertebral column (T12-L1), insertion-pectinate line. Innervation-Anterior rami of lumbar nerves L1-2. Actions-with the Psoas major, flexes the trunk at the hip and stabilizes the thigh Origin-Iliac fossa, insertion-lesser trochanter of the femur. Innervation-femoral nerve L3-4. Blood supply-Muscular branches of the medial femoral circumflex artery. Actionspowerful hip flexor and lateral rotator

What is a Horseshoe kidney? What is the most common presentation of horseshoe kidney? What is required for definitive diagnosis of Horseshoe kidney? What is the origin and insertion, innervation, blood supply and action of the Psoas major muscle? What is the origin and insertion, innervation, blood supply and action of the Psoas minor muscle? What is the origin and insertion, innervation, blood supply and action of the Iliacus muscle? What is the origin and insertion, innervation, blood supply and action of the Quadratus Lumborum muscle?

Which structures are retroperitoneal?

Origin-Transverse process of L3-5, insertion-lower border of the 12th rib. Innervation-Ventral branches of T12 and L1-4. Action-extends and laterally flexes vertebral column. Pancreas (except tail), Duodenum (second, third and fourth parts), ascending and descending colon, aorta, IVC, rectum, adrenal glands, and since this is the renal section-the kidneys!!!

Where are the kidneys located? Where do the ureters pass in relation to the uterine artery or vas deferens? What is the arterial supply to the kidneys? What is the venous return from the kidneys? What is unique about the Left Renal Vein? What are the structures of the Renal filtration system in the order in which filtrate would pass through? What is the direction of urinary drainage out of the kidneys? What types of epithelium line the Urethra?

Located at T12-L3 on the left and slightly lower on the right, embedded in Gerota's Fascia. Water goes under the bridge. Pass across the bifurcation of the common iliac and pass under the uterine arteries or vas deferens and then join the bladder on the posteroinferior side. Renal arteries which branch off the abdominal aorta Renal veins drain into the IVC It also drains blood from the left gonad and is longer than the right renal vein since it must cross the IVC Glomerulus surrounded by Bowman's capsule then proximal convoluted tubule the the straight portion of the proximal tubule, then thick descending, the Loop of Henle, then thick ascending limb, then the distal collecting tubule followed by the collecting duct. Renal pyramids to the renal papillae to the minor calyces to the major calyces Transitional epithelium as it exits the bladder, then stratified columnar epithelium followed by stratified squamous epithelium. Prostatic, Membranous (surrounded by striated muscle forming the voluntary external urethral sphincter), Bulbous then Pendulous (surrounded by Littre's glands. Does that mean it swings like a pendulum? Just wondering Much shorter so not really divided. Lined by stratified squamous and pseudostratified columnar epithelium. At the mid-portion it's surrounded by the striated muscle of the voluntary external urethral sphincter. Also surrounded by Littre's glands Primary filtering component, comprised of the glomerulus and Bowman's capsule Collection of dilated capillaries with a fenestrated endothelium, which emerge from the afferent arteriole and drain into the efferent arteriole

What are the anatomic divisions of the male urethra?

What are the anatomic divisions of the female urethra? What comprises a Renal Corpuscle?

What is the glomerulus?

What is Bowman's capsule? What is special about the visceral layer of Bowman's capsule?

Double-walled epithelial capsule enclosing the glomerulus. Consists of visceral and parietal layers with urinary space in between. Visceral layer filters the blood while the parietal layer covers the outside and is continuous with the proximal convoluted tubules. Specialized filtration lining that is made of Podocytes resting on a basement membrane, primary processes and foot processes. Yes! It's a fused basement membrane full of heparan sulfate which gives it a negative charge and makes it more impenetrable to things like albumin that are also negatively charged. Lined by simple cuboidal epithelium with a microvilli brush border. Interdigitations between the cells prevent loss of fluid and solutes Specialized system for absorption and secretion of electrolytes. Consists of the thick descending, thin descending, thin ascending and thick ascending loops (see more about transport later)

Is the basement membrane of the Glomerulus charged? Describe the histology of the Proximal Convoluted Tubule

Describe the histology of the Loop of Henle Describe the histology of the Distal Convoluted Tubule Describe the histology of the collecting tubule Describe the histology of the Collecting Ducts What doe Juxtamedullary nephrons do?

Lined by simple cuboidal epithelium without a brush border Lined by simple cuboidal epithelium. Transports urine from the functional nephron to the hilum Lined by columnar epithelium Exceptionally long Loops of Henle allow them to set up a hypertonic gradient in the kidney, regulating the production of concentrated urine Consists of macula densa cells in the proximal portion of the distal tubule and juxtaglomerular cells in the afferent and efferent arterioles. Controls GFR in response to BP in the afferent arterioles. JG cells secrete Renin leading to increased angiotensin II and aldosterone in response to decreased renal blood pressure, decreases sodium delivery to the distal tubule and increases sympathetic tone (Beta 1).

What is the Juxtaglomerular Apparatus?

What is the Macula Densa? What are Juxtaglomerular cells? What are extraglomerular mesangial cells?

Group of epithelial cells in the distal tubules that contact the afferent and efferent arterioles (JGA). Cells are sensitive to sodium concentration and rates of flow through the Distal Convoluted Tubule. Regulates GFR through locally active hormones. Specialized myoepithelial cells located on the afferent arterioles which act as baroreceptors. Monitor BP and maintain GFR through Renin release Contractile cells with receptors for angiotensin II and natriuretic factor allowing them to regulate glomerular flow. Transitional epithelium-can stretch and thin as it's distended. Smooth muscle in 3 layers arranged in multiple dimensions which evevntually become three distinct layers at the bladder's neck. Innermost is the involuntary sphincter. Diagram shows volume of ICF and ECF in the body. Osmolarity should be equal between ICF and ECF. Normovolemia is 42 liters total with 28L in the ICF. See Attachment 1 and walk through the diagram. ICF decreased, ECF increased, osm increased. Technically volume contraction and hypotonic but water more contracted that solute. No change in ICF, ECF decreased, no change in osm. Essenitally volume and solute contraction but equal contraction. ICF increased, ECF decreased, Osm decreased. Volume and solute contracted because not holding onto water and salt ICF unchanged, ECF increased, osm unchanged. Giving increasing amounts of fluid and solute so volume expansion. ICF decreased, ECF increased, osm increased. Volume expansion but solute pulls water into ECF ICF increased, ECF increased, osm decreased. Holding onto water and salt but water in excess of salt.

What types of cells line the bladder? Walk through a DarrowYannet Diagram (see following questions as well) What are clinical implications of Water deprivation? What are the clinical implications of Diarrhea? What are the clinical implications of Adrenal Insufficiency? What are the clinical implications of Infusion of isotonic NaCl? What are the clinical implications of high NaCl intake? What are the clinical implications of SIADH?

What is Renal Clearance? What does is mean if Cx<GFR? What does it mean if Cx>GFR? What does it mean if Cx=GFR? How is Inulin used to calculate GFR? How are Creatinine Clearance and GFR related?

Cx=UxV/Px Volume of plasma from which the substance is completely cleared per unit of time. C-clearance of X, U-urine concentration of X, V-urine flow rate, P-plasma concentration of X. (mL/minute) Net tubular reabsorption of X Net tubular secretion of X. Neither secretion or reabsorption of X Inulin can be used because it is freely filtered and neither reabsorbed nor secreted. GFR=Uinulin *V/Pinulin = Cinulin Creatinine Clearance is an approximate measure of GFR. Slightly overestimates GFR because there is moderate secretion of creatinine by the renal tubules. Clearance Ratio=Cx/Cinulin. 1 if equal to inulin. <1 means that clearance is less than inulin so either not filtered or filtered and reabsorbed. >1 means that clearance is more than inulin so filtered and excreted/activelly pumped. Fenestrated capillary endothelium. Glomerular basement membrane-composed of type IV and V collagen, laminin, heparan sulfate. Three layers-Lamina rara interna, lamina densa and lamina rara externa. Epithelial layer consists of podocytes which help form a barrier. Estimate using PAH clearance because it's filtered and actively secreted in the proximal tubule-thus all PAH is excreted. ERPF=UPAH *V/PPAH = CPAH RBF=RPF/(1-Hct). Note that ERPF underestimates RPF by about 10% so RBF is overestimated. Dopamine dilates the vessels and suppresses sodium reabsorption in the proximal tubule by inhibiting the action of the basolateral Na/K ATPase. Released directly by the proximal tubule in response to an increase in BP resulting in decreased RBF and GFR.

What is the Clearance ratio (with Inulin)?

What forms the Glomerular Filtration Barrier? How can you estimate Effective Renal Plasma Flow (ERPF)? How do you estimate Renal Blood Flow?

What is Dopamine's effect on the nephron?

How does Afferent arteiole constriction affect RPF, GFR and Filtration Fraction? How does Efferent arteiole constriction affect RPF, GFR and Filtration Fraction? How does increased Plasma protein affect RPF, GFR and Filtration Fraction? How does decreased plasma protein affect RPF, GFR and Filtration Fraction? How does constriction of the ureter affect RPF, GFR and Filtration Fraction?

Decreased RPF, Decreased GFR, No change in filtration fraction

Decreased RPF, Increased GFR, increased filtration fraction

No change in RPF, decreased GFR and filtration fraction

No change in RPF, increased GFR and increased filtration fraction

No change in RPF, decreased GFR, decreased filtration fraction Two autoregulatory mechanisms-stretch/myogenic and tubuloglomerular feedback. Stretch-when BP increases, arterioles are stretched leading to vasoconstriction in the afferent arteriole thus maintaining constant RBF. Tubuloglomerular feedback- increased arterial pressure leads to increased RBF and increased flow to the distal tubule which is sensed by the macula densa. This results in constriction of the afferent arteriole, attenuating RBF. Fraction of plasma filtered across the membrane of the glomerular capillaries. FF=GFR/RPF. Normal FF is about 20% GFR * Plasma concentration. Ability to dilute urine. Free water (Ch2o)= V-Cosm (Cosm=Uosm*V/Posm) Thick ascending limb and early distal tubule. NaCl is reabsorbed without reabsorption/permeability to H2O. ADH causes retention of free water so Ch2o<0. Concentrated urine

Describe autoregulation of blood flow in the kidneys

What is Filtration Fraction? What is Filtered Load? What is Free Water Clearance? Where does free water clearance occur? How does ADH affect Ch2o?

How can you calculate Excretion rate? How can you calculate Reabsorption? How can you calculate Secretion?

Excretion rate= V*Ux Reabsorption=Filtered-Excreted Secretion=Excreted-Filtered Should be completely reabsorbed in the proximal tubule by Na/Glucose cotransport. At a plasma glucose >160-200 mg/dL you start to see glucosuria because the transport is being overwhelmed. At 350 mg/dL, all transporters are fully saturated so clinical glucosuria develops Shouldn't be cleared. Na dependent transporters in the proximal tubules reabsorb amino acids with multiple carrier systems. Deficiency of neutral amino acid (tryptophan) transporter. Causes Pellagra. Unit composed of the glomerulus, through which fluid is filtered, and the tubular system where filtered fluid is modified through the reabsorption and secretion of various solutes to produce urine.

How is glucose reabsorbed and how does it go wrong?

How are amino acids cleared? What is Hartnup's Disease?

Define the Nephron. How do tubules of the nephron maintain low intracellular Na and the Na gradient across the tube?

Na/K ATPase on the basolateral membrane maintains the Na gradient from the lumen to the cell. The proximal tubule is the major site of reabsorption, based on the transmembrane Na gradient. Reabsorbs all filtered glucose and amino acids via cotransport with Na. Reabsorbs most bicarb, sodium, chloride and water. Isotonic absorption. Generates and secretes ammonia which buffers secreted H. Na and H are exchanged, Cl is absorbed in exchange for bicarb. CO2 and H2O cross the membrane and are made into bicarb by carbonic anhydrase. That is excreted and then made into CO2 and H2O again.

Describe transport across the luminal and basolateral side of the Proximal Tubule (see attachment 2). How is bicarb regulated/excreted in the Proximal tubule? How do Angiotensin II and Atrial Natriuretic Peptide act on the Proximal tubule?

Ang II stimulates Na reabsorption which ANP blocks Na reabsorption.

How does Parathyroid hormone affect excretion/absorption?

PTH inhibits Na/Phosphate cotransport resulting in phosphate excretion. Thin descending loop absorbs about 20% of filtered water but no solute via medullary hypertonicity. Thin ascending limb is impermeable to water and has no significant reabsorption. Thick ascending limb is the diluting segment of the tubular system. Actively absorbs Na, K and Cl (NK2Cl). This induces the paracellular absorption of Mg and Ca because K leaks back into the lumen creating a positive charge in the lumen. It's impermeable to H2O so it dilutes urine. Impermeable to water and urea. Early distal tubule actively reabsorbs Na and Cl making urine hypotonic. PTH increases Ca/Na exchange thus increasing Ca absorption. Principle cells reabsorb Na and H2O and secrete K via the Na/K ATPase. Intercalated cells secrete H and reabsorb K and HCO3. Inserts more Na channels on the luminal side increasing Na reabsorption. Acts at V2 receptors and inserts aquaporins H2O channels into the luminal side. U shaped capillaries which are freely permeable to H2O and solutes except protein. Situated close to the Loop of Henle. Enables the cortico-medullary osmolar concentration gradient. Preserves hyperosmolarity of renal medulla to maintain absorption. Solute is being reabsorbed more slowly than water or there is net secretion of solute. Solute and water are reabsorbed at equal rates Solute is reabsorbed more quickly than water.

Describe transport across the Loop of Henle.

Describe transport across the distal convoluted tubule. Describe transport across the late distal tubule and collecting ducts. How does Aldosterone affect the collecting ducts? How does ADH affect the collecting tubules?

What is the Vasa Recta? What does it mean if Tubular Fluid (TF)/Plasma (P) >1? What does it mean if TF/P=1 What does it mean if TF/P<1

What is the function of Angiotensin II?

What is the function of ANP?

Affects baroreceptors, limits reflex bradycardia which would normally accompany pressors. Constricts efferent arteriolesincreased FF to maintain GFR in low volume states. Increases proximal tubule Na/H activity and can stimulate thirst in the hypothalamus. Released from the atria in response to low volume. Relaxes vascular smooth muscle via cGMP resulting in increased GFR and decreased renin. Regulates osmolarity and responds to low blood volume which takes precedence over osmolarity. Increases H2O channel insertion in principle cells resulting in H2O reabsorption. Increases Na channel, increases Na/K pump insertion in principle cells, enhances K and H excretion creating a favorable Na gradient for Na and H2O reabsorption. Primarily regulates blood volume. Glycoprotein hormone that stimulates RBC production in response to hypoxia. Released from endothelial cells of peritubular capillaries. Epo receptors are on proerythroblasts which mature in response. Active Vitamin D. Proximal tubule cells convert 25-OH-Vitamin D to the dihydroxy form. This increases intestinal reabsorption of both calcium and phosphate. PTH directly acts on the kidney to increase renal calcium reabsorption and decrease renal phosphate excretion. Also stimulates proximal tubule cells to make 1, 25 dihydroxycholicalciferol. Secreted by JG cells in response to increased renal arterial pressure and increased renal sympathetic discharge (Beta 1 effect). Stimulates Angiotensin Paracrine secretion of PGE2 vasodilates the afferent arterioles to increase GFR. NSAIDs can cause acute renal failure by inhibiting PGE thus preventing the arterioles to vasodilate to maintain GFR.

What is the function of ADH?

What is the function of Aldosterone?

What is Erythropoietin? What is 1, 25-(OH)2 Vitamin D? How does Parathyroid Hormone affect the kidney's endocrine function?

What is Renin?

What do prostaglandins do in the kidney?

Where do each of the above hormones act on the kidney? (this rehashes all the functions as well)

ANP is secreted in response to increased atrial pressure. Causes increased GFR and increased Na filtration. Acts right at the beginning of proximal convoluted tubule. PTH is secreted in response to decreased plasma Ca, increased plasma PO4 or decreased plasma vitamin D. Causes increased Ca reabsorption in the distal convoluted tubule, decreased PO4 reabsorption at the proximal convoluted tubule, increased Vitamin D production and increased Ca and PO4 absorption from gut. Renin is released from the JGA and acts on the distal convoluted tubule. Ang II is synthesized in response to decreased BP and causes the efferent arteriole constriction thus increasing GFR and FF but with compensatory Na reabsorption. ADH is secreted in response to increased plasma osmolarity and decreased blood volume. Binds receptors on principal cells causing increased aquaporins. Acts on collecting ducts. Aldosterone is secreted in response to decreased blood volume and increased plasma K, resulting in increased Na reabsorption and increased Kand H secretion. Acts on collecting duct. Insulin deficiency (decreased Na/K ATPase), Beta Adrenergic antagonists (decreased Na/K ATPase), Acidosis or severe exercise (K/H exchange), Hyperosmolarity, Digitalis (blocks Na/K ATPase), Cell lysis Insulin (increased Na/K ATPase), Beta Adrenergic agonists (increased Na/K ATPase), Alkalosis (K/H exchanger), Hypoosmolarity. About 7.4 Decreased Bicarb. Compensation by hyperventilation Increased bicarb. Compensation by hypoventilation. Respiratory compensation in response to metabolic acidosis. PCO2=1.5 (HCO3) +8 (+/-2)

What causes K shift out of cells?

What causes K shift into cells? What is normal pH of blood? What is metabolic acidosis? What is metabolic alkalosis? What is Winter's Formula?

How much should PCO2 increase when bicarb increases? What is respiratory acidosis? What is respiratory alkalosis? What are some causes of Respiratory Acidosis? What are some causes of Anion Gap Metabolic Acidosis? What are some causes of nonAnion Gap Metabolic Acidosis? What are some causes of Respiratory Alkalosis? What are some causes of Metabolic Alkalosis? What is Type 1 (Distal) Renal Tubular Acidosis? What is Type 2 (proximal) Renal Tubular Acidosis? What is Type 4 (hyperkalemic) Renal Tubular Acidosis?

PCO2 increases 0.7 mmHg for every 1 mEq/L HCO3 Increased PCO2. Compensation with increased bicarb absorption Decreased PCO2. Compensate with less bicarb reabsorption. Hypoventilation-Airway obstruction, acute lung disease, chronic lung disease, opiods/narcotics, weak respiratory muscles. MUDPILES-Methanol, Uremia, Diabetic Ketoacidosis, Paraldehyde or Phenformin, Iron tablets or INH, Lactic Acidosis, Ethylene glycol, Salicylates

Diarrhea, Glue sniffing, Renal Tubular Acidosis, Hyperchloremia Hyperventilation-(early) high altitude exposure, Aspirin ingestion (early) Diuretic use, vomiting, antacid use, hyperaldosteronism. Defect in the collecting tubule's ability to excrete H. Associated with hypokalemia and risk for Ca containing kidney stones. Defect in proximal tubule HCO3 reabsorption. Associated with hypokalemia and hypophosphatemic rickets. Hyperaldosteronism or lack of collecting tubule response to aldosterone causes hyperkalemia- inhibition of ammonia excretion in proximal tubule. Leads to decreased urine pH due to decreased buffering capacity. Stimulated Mineralocorticoid receptors on Principal Cells. This increases their permeability to sodium and potassium by adding Na channels and increases enzymes of the citric acid cycle thus increasing ATP to pump Na/K out the basolateral side. Also stimulated alpha-intercalated cells to secrete more H, thus regulating plasma HCO3 and acid-base balance. Na- (HCO3 + Cl) normal =10-12

How does Aldosterone act on the Late Distal Tubule? How do you calculate the anion gap?

Why does an anion gap occur?

What is a delta delta? How do you calculate a delta delta? How do you interpret a delta delta? How much should CO2 rise in response to increased bicarb?

Secondary to a loss of bicarb or an excess of acid. Essentially there's a lot of something in the blood that's neither Na, HCO3 or Cl that isn't being accounted for so there's a gap in the math. Comparison of change in anion gap to change in bicarbonate. Can tell you what there is in excess if there is a mixed acid base disorder. Change in anion gap = AG-12. Change in Bicarb = 24measured HCO3. Delta delta is ratio of the two AG>HCO3 - Metabolic alkalosis + metabolic acidosis. AG<HCO3 -Wide AG + non AG metabolic acidosis. Equal-wide anion gap metabolic acidosis. For every 10 mmol/L rise in HCO3, PCO2 should increase 6mmHg Excretes harmful waste (urea, creatinine, uric acid, etc.), Maintains acid-base homeostasis, Reabsorbs essential substances, Regulates water and sodium metabolism, Maintains vascular tone, Produces erythropoeitin, Maintains calcium homeostasis. Blood in the urine. Causes fro, the upper urinary tract- renal stone, glomerulonephritis (dysmorphic RBC's), Renal cell carcinoma. Causes from the lower urinary tract- Infection, transitional cell carcinoma, benign prostatic hyperplasia. Drug related causes-anticoagulants, cyclophosphamide (hemorrhagic cystitis and risk for transitional cell carcinoma) Protein >150 mg/24 hours or >30 mg/dL via dipstick. Dipstick-detects albumin only. Sulfosalicylic acid-detects albumin and globulins. Protein <2g/24 hour, not associated with renal disease. Causes are fever, exercise, CHF. Postural-only occurs when standing. First void in the morning has no protein but subsequent during the day does have protein. No association with renal disease.

What are the general functions of the Kidneys?

What is hematuria and what are some common causes? What is Proteinuria? What are diagnostic tests for proteinuria? What is Functional Proteinuria? What is Orthostatic Proteinuria?

What is Overflow proteinuria?

Variable protein loss with LMW proteins. Essentially the amount filtered is greater than the tubular reabsorption. Causes are multiple myeloma with Bence Jones proteinuria, Hemoglobinuria from intravascular hemolysis, myoglobinuria from crush injuries, McArdle's glycogenosis and increases in serum creatine kinase. BUN is a normal end product of amino acid and pyrimidine metabolism that is produced by the liver in the urea cycle. It is filtered in the kidneys and partially reabsorbed in the proximal tubule (amount reabsorbed is flow dependent). GFR, protein content of the diet, proximal tubule reabsorption and the functional status of the urea cycle. Decreased cardiac output (decreased GFR), increased protein intake/breakdown, increased tissue catabolism (burns, surgery, etc), acute glomerulonephritis, acute or chronic renal failure, postrenal disease. Increased plasma volume (pregnancy, SIADH, etc), decreased urea synthesis (cirrhosis, Reye syndrome, fulminant liver failure), decreased protein intake (Kwashiorkor, starvation gluconeogenesis in kideys) Metabolic end product of creatine in muscle. Filtered in the kidneys and not reabsorbed or secreted. Serum concentration varies with age and muscle mass. Increased serum BUN and creatinine 15. Urea is filtered and partly reabsorbed whereas Creatinine is filtered entirely. BUN:Cr ratio depends on changes-can be prerenal, renal or postrenal Increased BUN and creatinine caused by something before the kidneys. Most common cause is decreased cardiac output/hypoperfusion of the kidneys decreasing GFR. BUN:Cr >15 because proportionately more Urea is reabsorbed from the low flow rate. Increased BUN and Cr from parenchymal damage to the kidneys. Some causes are Acute Tubular Necrosis and Chronic Renal Failure. BUN:Cr <15. Both are filtered, there is extrarenal loss of urea and urea may not be reabsorbed as well.

What is Serum BUN? What does serum BUN depend on?

What are some causes of increased BUN?

What are some causes of decreased BUN?

What is Serum Creatinine? What is Azotemia? What is a normal Serum BUN: Creatinine ratio?

What is Prerenal Azotemia and what are some causes?

What is Renal Azotemia and what are some causes?

What is Postrenal Azotemia and what are some causes? What is a normal Cr Clearance?

Increased BUN and Cr from urinary obstruction below the kidneys. Prostate hyperplasia, blockage or ureters by stones or cancer. Serum BUN:Cr ratio >15. Obstruction to flow decreases GFR resulting in back diffusion of urea (not Cr) into blood and a disproportionate increase in BUN. 97-137 mL/minute. Less than 100 mL/minute is abnormal. Normal pregnancy (Increased plasma volume means increased GFR), early diabetic glomerulopathy (constricted efferent arteriole from hyaline sclerosis causing increased GFR) Elderly people (decreasing GFR with age), Acute and Chronic Renal disease (ARF from tubular sclerosis, CRF from diabetic glomerulopathy)

What are some causes of increased Cr Clearance? What are some causes of decreased CR Clearance? What does dark yellow color indicate in Urinalysis? What does Red or Pink color indicate in Urinalysis? What does smoky-colored urine indicate? What does black urine after exposure to light indicate?

Concentrated urine, Bilirubinemia, Increased UBG, Vitamins Hematuria, hemoglobinuria, myoglobinurua, drugs (phenazopyridine), porphyria Acid pH converts Hb to hematin. Common in nephritic glomerulonephritis Alkaptonuria. Deficiency of homogentisate oxidase resulting in buildup of homogentisic acid Cloudy urine with alkaline pH is normal, probably from phosphates. Cloudy urine with acid pH is normal probably from uric acid. Otherwise, bacteria, WBC's, Hb, myoglobin Urine concentration and dilution. SG>1.023 indicates urine concentration and excludes intrinsic renal disease. Hypotonic <1.015. Fixed SG (1.008-1.010) may indicate a lack of concentration and dilution possibly renal failure. Determined by diet and acid base status of person. Vegan often have alkaline pH, meat eaters have acidic pH. An alkaline pH plus strong ammonia smell indicates a urease producing pathogen.

What does clarity of the urine indicate?

What does the specific gravity of the urine indicate?

What does the pH of the urine indicate?

What does glucose indicate in the urine? What does microalbuminuria indicate? What do ketones in the urine indicate? What does bilirubin in the urine indicate?

Increased serum glucose means glucosuria and DM. Normal serum glucose and glucosuria can happen in normal pregnancy, benign glucosuria First sign of diabetic nephropathy Acetone and acetoacetic acid. Ketonuria from DKA, starvation, ketogenic diets, pregnancy and isopropyl alcohol poisoning Bilirubinuria may indicate hepatitis or obstructive jaundice Trace amounts are normal. No UBG with increased urine bilirubin may be obstructive jaundice. Increased UBG with absent urine bilirubin means extravascular hemolytic anemia. Increased UBG with increased urine bilirubin means hepatitis Hematuria from renal stone, hemoglobinuria from intravascular hemolytic anemia, myoglobinuria from increased serum creatine kinase and crush injuries. Nitrites produced by nitrate reducing uropathogens. Esterase in neutrophiles (pyuria). Infections from urethritis, cystitis, pyelonephritis. Sterile pyuria-Chalmydia trachomatis urethritis, TB, drug induced interstitial nephritis Bacteria-UTI, RBC's-hematuria from renal stones, cancer, glomerulonephritis. Dysmorphic RBC's-hematuria of glomerular origin. Neutrophils-pyuria from UTI or sterile pyuria. Oval fat bodies-renal tubular cells with lipids (nephrotic syndrome) Casts are formed in tubular lumens in the kidney and are composed of a protein matrix with entrapped cells, debris or protein leaking through the glomeruli. Proves renal origin of the disease. Acellular, ghost like cast containing protein. Only significant if there is accompanying proteinuria Nepritic type of glomerulonephritis resulting in a cast made of RBC's Cast of WBC's indicating acute pyelonephritis, acute tubulointerstitial nephritis

What does Urobilinogen indicate? What does blood in the urine indicate? What do nitrites in the urine indicate?

What does Leukocyte Esterase in the urine indicate?

What do cells in the urine indicate?

What do casts indicate in the urine? What is a hyaline cast? What is a RBC Cast? What is a WBC cast?

What is a renal tubular cast? What is a fatty cast? What is a Waxy/Broad cast?

Cast of a sloughed off renal tubule. Indicates acute tubular necrosis Cast of cells with lots of lipid. Indicates nephrotic syndrome Refractile, acellular cast seen in chronic renal failure. Calcium oxalate crystals-pure vegan diet, ethylene glycol poisoning, calcium oxalate stone. Uric acid crystalshyperuricemia from gout or massive cell destruction after chemotherapy. Triple phosphate crystals-sign of UTI from urease producing pathogens like Proteus. Cystine crystalshexagonal crystals seen in Cystinuria Renal cortex receives 90% of the blood supply. Medulla is relatively ischemic from reduced blood supply. Renal vessels are all end arteries with no collateral circulation so occlusion of any branch produces infarction. Afferent blood flow is controlled by renal-derived PGE2 and renin. Efferent blood flow is controlled by ATH (vasoconstrictor) Loss of charge of the glomerular basement membrane which produces selective proteinuria.

What types of crystals can be seen in the urine and what do they indicate?

Describe the blood supply to the kidney. What is minimal change disease? What protein produces the charge on the glomerular basement membrane? What are some causes of GBM thickening?

What do Visceral Epithelial Cells do in the glomerulus?

Heparan Sulfate Deposition of immunocomplexes such as in membranous glomerulopathy. Increased synthesis of Type IV Collagen such as in DM. Production of the GBM. Contain podocytes and slit pores between podocytes which serve as a distal barrier to prevent protein loss in the urine. Podocytes fuse in nephrotic syndrome, no matter what the cause. Support the glomerular capillary. Can release inflammatory mediators and proliferate-IgA glomerulopathy has mesangial immune complex deposits. Lining cells of Bowman's capsule. Proliferation causes crescents that encroach upon and destroy the glomerulus.

What do Mesangial Cells do in the glomerulus? What do parietal epithelial cells do in the glomerulus?

What is Renal Dysplasia? What is Juvenile Polycystic Kidney Disease? What other types of conditions are seen in Juvenile Polycystic Kidney Disease?

Most common cystic disease in children. See abnormal development of one or both kidneys with abnormal structures persisting in the kidneys (cartilage, immature collecting ductules). Present as enlarged, cystic, unilateral or bilateral flank mass. May lead to chronic renal failure. AR disease. Bilateral cystic disease with cysts involving all parts of the nephron in the cortex and medulla. Bilaterally palpable kidneys. Cysts present in liver. Associated with congenital hepatic fibrosis which leads to portal hypertension. Also associated with oligohydramnios and Potter's Syndrome. AD disease with defect on chr 16. Bilateral cystic disease with the cysts involving all parts of the cortex and medulla. Develop chronic renal failure a lot of the time. Cysts may be present in the liver, pancreas and spleen. Also have intracerebral Berry aneurysms. May cause hemorrhage if hypertension results in rupture, intracerebral hemorrhage and lacunar infarcts. Other associations are sigmoid diverticulosis, hematuria, mitral valve prolapse, and risk for developing renal cell carcinoma. Multiple cysts in the collecting ducts present in the medulla. See striations in the papillary ducts of the medulla (swiss cheese appearance). Recurrent UTI's, hematuria and renal stones. Most commonly caused by renal dialysis. Tubules become obstructed by interstitial fibrosis or oxalate crystals. Small risk for renal cell carcinoma. Most common adult renal cyst. Derived from tubular obstruction. May cause hematuria and may resemble renal cell carcinoma. Needle aspiration will distinguish it from RCC Only a few glomeruli are abnormal All glomeruli are abnormal

What is Adult Polycystic Kidney Disease?

What other conditions are associated with Adult PKD?

What is Medullary Sponge Disease? What is Acquired Polycystic Kidney Disease?

What are simple retention cysts? What is Focal Glomerulonephritis? What is Diffuse Glomerulonephritis?

What is Proliferative Glomerulonephritis? What is Membranous Glomerulonephropathy? What is Membranoproliferative Glomerulonephritis? What is Focal Segmental Glomerulosclerosis? What is Crescentic Glomerulonephritis? What is Primary Glomerular Disease? What is Secondary Glomerular Disease? Look at Golijan page 400 and go through all the histology What does a Linear pattern indicate on Immunofluorescence? What does a Granular or Lumpy Bumpy appearance indicate on Immunofluorescence?

>100 nuclei in affected glomeruli Thick GBM, no proliferative change

Thick GBM, hypercellular glomeruli Fibrosis involving only a segment of the involved glomerulus Proliferation of the parietal cells around the glomerulus (in Bowman's Space, thus forming a crescent) Involves only glomeruli and no other target organs. Essentially something like minimal change disease. Involves glomeruli and other organs, e.g. SLE

Ya, definitely do that :-) Antibodies line upagainst evenly distributed antigens in the GBM. Think Goodpasture's Syndrome

What do immune complexes look like on Electron Microscopy? How does Type III Immune complex disease cause glomerular disease? How does something like Goodpasture's Disease cause glomerular damage?

Think immunocomplex deposits in the glomerulus forming lumps of Ig. Not attached to the GBM. Electron dense giving them a dark color. Subendothelial are trapped between the endothelial cell and GBM. Subepithelial has passed through the GBM but is stuck in the podocytes. Intramembranous is within the GBM and Mesangial is within the mesangium. Circulate and deposit in glomeruli or develop in situ. Immune complexes then activate complement, procude C5a which is chemotactic to neutrophils which attack the GBM. Anti GBM antibodies attack the glomerular basement membrane

How does T Cell production of cytokines damage the GBM? What are clinical manifestations of glomerular disease?

Cytokines cause the GBM to lose its negative charge. Cytokines also damage podocytes causing them to fuse. Nephritic syndrome, nephrotic syndrome and chronic glomerulonephritis Glomerular injury primarily occurs due to neutrophils which damage See hypertension from salt retention, periorbital puffiness from salt retention, oliguria (decreased GFR from inflamed glomeruli) and Hematuria. The hematuria features dysmorphic RBC with irregular membranes from inflamed glomeruli with IC deposition. Often see neutrophils in the sediment, especially if immune complex. RBC casts are a key finding, and occasionally there are WBC casts. Proteinuria>150mg/day but less than 3.5 g/day. Azotemia with BUN:Cr ratio >15 because tubular function is intact in acute glomerulonephritis Most common nephropathy, mostly nephritic. Increased mucosal synthesis and decreased clearance of IgA with increased serum IgA. Produces Focal Proliferative Glomerulopathy. Also see Mesangial IgA immune complex deposits with granular immunofluorescence. IC's activate the alternative complement pathway. Henoch Schonlein Purpura Episodic hematuria and hypertension following URI because of increased IgA deposits. Most common type of post-infectious glomerulonephritis, usually after group A strep infection of skin (scarlet fever) or pharunx. Subepithelial immune complex deposits with granular immunofluorescence. IC's activate the alternative complement pathway. See a diffuse proliferative pattern with neutrophilic infiltrate. Hematuria, 1-3 weeks following group A strep infection by a nephritogenic strain (never produces rheumatic fever). Causes periorbital edema from sodium retention not hypoalbuminemia, transient, sometimes severe hypertension.

Describe the pathophysiology of Nephritic Syndrome? What are some lab findings in Nephritic syndrome?

What is IgA Nephropathy (Berger's Disease)? What does Berger's disease often immitate? What happens after a URI in Berger's disease?

What is Post-Streptococcal Glomerulonephritis?

How does Post-Streptococcal Glomerulonephritis present?

What lab tests are indicative of Post-Strep Glomerulonephritis?

Increased DNAase B titers. ASO is degraded by oil in the skin and is thus not increased. Streptozyme test is positive (antiDNAase B, ASO, anti-AH and anti-NAD antibodies). Most common type of glomerular disease in SLE. Subendothelial IC deposits with granular immunofluorescence. DNA-anti-DNA IC's activate the classical complement pathway. See "wire looping of capillaries" as well as neutrophil infiltration with hyaline thrombi in capillary lumens.

What is Diffuse Proliferative Glomerulonephritis? What does the serum ANA test look like in Diffuse Proliferative Glomerulonephritis? How do you treat Diffuse Proliferative Glomerulonephritis? What is Rapidly progressive Crescentic Glomerulonephritis? Which diseases are associated with Rapidly Progressive Crescentic Glomerulonephritis? What HLA type is common in Goodpasture's syndrome? How do you treat Goodpasture's syndrome?

Serum ANA has a rim pattern, corresponding to the presence of anti-ds DNA antibodies

Corticosteroids and Cyclophosphamide Clinical syndrome that may be either primary or secondary disease. See a rapid loss of renal function that progresses to acute renal failure within weeks. May or may not be associated with crescent formation.

Goodpasture's syndrome, microscopic polyarteritis (p-ANCA), Wegener's granulomatosis (c-ANCA)

80% are HLA-BR2 positive Plasma exchange to remove antibodies, immunosuppressive therapy with steroids and cyclophosphamide or renal transplant Glomerular injury due to cytokines not neutrophils. Cytokines released from T Cells destroy the negative charge of the membrane thus allowing protein leak. They also cause the podocytes to fuse together.

What is Nephrotic Syndrome?

What are the key findings in nephrotic syndrome? What type f kidney disease does Diabetic Glomerulopathy cause?

Proteinuria >3.5 g/24 hr, pitting edema and ascited due to hypoalbuminemia. Increased risk for spontaneous peritonitis from strep pneumoniae. Sometiems there is hypertension from salt retention. Hypercoagulability due to loss of Antithrombin III causing potential for renal vein thrombosis. Hypercholesterolemia from increased synthesis (after albumin loss). Hypogammaglobulinemia from protein loss. Fatty casts with maltese crosses and oval fat bodies. Nephrotic syndrome with Nodular Glomerulosclerosis (Kimmelstiel-Wilson disease). Risk factors are poor glycemic control, hypertension and high correlation with coexisting diabetic retinopathy. Nonenzymatic glycosylation of the GBM, also affecting the tubule basement membranes. Results in increased vessel and tubular permeability to proteins. NEG of the afferent and efferent arterioles also results in hyaline arteriolosclerosis (efferent first). There is also osmotic damage to the glomerular capillary endothelium because glucose is converted to sorbitol by aldolase reductase resulting in an osmotic gradient. Selective hyaline arteriolosclerosis of the efferent arterioles results in increased GFR and causes hyperfiltration damage to the mesangium. Increased Type IV collagen deposition in the GBM, tubular basement membrane and mesangium results in a microangiopathic state. Fusion of podocytes, afferent and efferent hyaline arteriolosclerosis, nodular masses of type IV collagen and trapped proteins in the mesangium

What is the pathogenesis of Diabetic Glomerulopathy? What is Diabetic Microangiopathy? What microscopic changes are seen in Diabetic Glomerulopathy? What lab values are significant in Diabetic Glomerulopathy? Are there any other diseases of the kidney associated with Diabetic Glomerulopathy? What is renal amyloidosis?

Microalbuminuria

Renal papillary necrosis and acute or chronic pyelonephritis Amyloid deposits in the kidney secondary to primary or secondary amyloidosis

What is Alport's Syndrome?

X-Linked recessive (sometimes AR or AD) mutations in A chains of type IV collagen in the GBM. Lipid accumulates in VEC's producing foam cells. Also see sensorineural hearing loss and ocular abnormalities Benign familial hematuria. AD disorder with extremely thin basement membranes in the setting of normal renal functin. See mild proteinuria and persistent microscopic hematuria Rapidly progressive glomerulonephritis, focal segmental glomerulosclerosis, type I membranoproliferative glomerulonephritis, membranous glomerulopathy, type IV diffuse proliferative glomerulonephritis in SLE, IgA nephropathy.

What is Thin Basement Membrane Disease?

What are the common causes of Chronic Glomerulonephritis? What are gross and microscopic findings in chronic glomerulonephritis?

Shrunken kidenys with glomerular sclerosis and tubular atrophy Most often caused by prerenal azotemia due to hypovolemia. Ischemia damages endothelial cells decreasing vasodilators and increasing vasoconstrictors, thus worsening the situation and further decreasing GFR. Ischemia also damages tubular cells which then detach into the lumen, cause obstruction and produce pigmented renal tubular cell casts. The casts further obstruct the lumen increasing tubular pressure, decreasing GFR and pushing fluid into the interstitium resulting in oliguria. Straight segment of the Proximal tubule (part of the degree most susceptible to hypoxia), Medullary segment of the thick ascending limb (location of the NK2C transporter), and the Tubular basement membrane (interferes with renal tubular cell regeneration)

What is ischemic Acute Tubular Necrosis?

What segments of the nephron are damaged in ischemic ATN?

What is Nephrotoxic Acute Tubular Necrosis? What is the epidemiology of Acute Tubular Necrosis?

What is Acute Renal Failure? What are some causes of Acute Renal Failure? What is RPGN?

ATN from nephrotoxic substances. Aminoglycosides are most common, radiocontrast agents and heavy metal poisoning are also causes. Most commonly see oliguria, occasionally polyuria. This primarily damages proximal tubule while the tubular basement membrane is intact. Also see pigmented renal tubular cell casts, hyperkalemia and anion gap metabolic acidosis, increased BUN and Cr with ratio of BUN:Cr <15. Often have issues with hypokalemia in the diuresis phase. 10% of ICU patients, 40% iatrogenic, 20% of patients with sepsis and >50% of patients with septic shock Acute suppression of renal function developing in 24 hours, accompanied by oliguria or anuria. Most commonly caused by ATN. Postrenal obstruction, vascular disease (malignant htn), RPGN, drugs, DIC, urate nephropathy. Rapidly progressive glomerular nephritis Treat prerenal azotemia-volume expansion if hypovolemic to increase renal blood flow. Low dose dopamine. Fenoldopam (dopamine Alpha-1-receptor agonist), Dialysis Acute or chronic inflammation of tubules and interstitium. May be caused by acute pyelonephritis, drugs, infections (legionaire's, leptospirosis), SLE, lead poisoning, Urate nephropathy and multiple myeloma. E Coli is most common followed by Enterococcus. Risk factors are indwelling catheter, obstruction, medullary sponge kidney, DM, pregnancy and sickle cell Intravesical portion of the ureter is not compressed during micturition so urine refluxes up. Causes ascending infection into the renal pelvis and parenchyma. Urine output <400 mL/day or less than 20 mL/hr. Prerenal azotemia, acute glomerulonephritis, acute tubular necrosis/renal azotemia, and postural azotemia. Urine osm <350 mOsm/kg indicates poor concentrating ability and thus tubular dysfunction FENa = (Una * PCr)/(PNa * Ucr) *100

How do you treat Acute Renal Failure?

What is Tubulointerstitial Nephritis? What are common causes of acute pyelonephritis?

How does vesicoureteral reflux cause pyelonephritis? What is Oliguria? What are common causes of Oliguria? What does decreased Urine Osm indicate? How do you calculate a FENa?

What does a FENa less than 1% indicate? What does a FENa greater than 2% indicate?

Sodium filtration closely mimics creatinine filtration. FENa less than 1% means good tubular function Tubular dysfunction. Good predictor of ATN UNa<20 mEq/L indicates good tubular function aka you're not dumping salt like crazy. UNa >40 mEq/L indicates poor tubular function aka you're not reabsorbing salt. ATN usually presents with pigmented tubular casts. In postrenal azotemia, the sediment is usually normal.

What can UNa tell you about tubular function? How do you distinguish postrenal azotemia from ATN? What should you suspect if there is staph a. cultured in the urine? What are gross and microscopic findings in pyelonephritis? What are the clinical and lab findings in pyelonephritis? What are complications of Acute Pyelonephritis? What are pathological findings in Chroninc Pyelonephritis? What pathological findings are seen in obstructive Chronic Pyelonephritis? What are microscopic findings of Chronic Pyelonephritis? What can reflux nephropathy cause in children? What drugs are associated with acute drug induced ATN?

Hematogenous spread of the infection to the kidneys. Grayish white areas of abscess formation in the cortex and medulla. Microabscesses form in the tubular lumens and interstitium. Clinical-spiking fever, flank pain, frequency and dysuria. LabWBC casts, pyuria, bacteruria, hematuria Chronic Pyelonephritis, Perinephric Abscess, Renal Papillary necrosis, septicemia with endotoxic shock U shaped cortical scars overlying a blunt calyx, visible on IV pyelogram. Uniform dilation of the calyces and diffuse thinning of cortical tissue. Chromic inflammation with scarring of the glomeruli. Tubular atrophy-tubules contain eosinophilic material resembling thyroid tissue (thyroidization)

Hypertension Penicillin esp. methicillin. Rifampin, sulfonamides, NSAIDs, diuretics

What is the pathogenesis of Drug induced ATN?

Combination of Type I and IV hypersensitivity. Abrupt onset of fever, oliguria and rash that resolves with withdrawal of the drug. Causes tubular disease with a BUN:Cr <15, eosinophilia and eosinophiluria Chronic drug induced Tubulointerstitial nephritis. Chronic use of Acetominophen with Aspirin because Acetominophen causes free radical damage while aspirin inhibits renal synthesis of PGE2 leaving AT II unopposed. Renal papillary necrosis-sloughing of renal papillae producing gross hematuria, proteinuria and colicky flank pain. Ring defect where papillae used to reside. Hypertension, CRF and Renal pelvic and bladder transitional cell carcinomas. Deposition of Urate crystals in the tubules and interstitium. May be caused by massive release of purines (often after chemo), lead poisoning or gout. Decreased excretion of uric acid from the lead. Also direct toxic effects cause TIN

What is Analgesic Nephritis?

What are complications of Analgesic Nephritis?

What is Urate Nephropathy? How does lead poisoning cause Urate Nephropathy? What is seen microscopically in Urate Nephropathy resulting from lead poisoning?

Nuclear acid-fast inclusions in the proximal tubule Bence Jones light proteins are toxic to the tubular epithelium and result in tubular casts. Casts obstruct the lumen and incite a foreign body giant cel reaction of the tubules and interstitium, leading to renal failure. Nephrocalcinosis from bone breakdown/hypercalcemia also causes metastatic calcification of the basement membrane collecting tubules. Finally, BJ proteins may be converted to amyloid and cause primary amyloidosis resulting in nephrotic syndrome. Normocytic anemia with low corrected reticulocyte count. Due to decreased Erythropoietin production. Also see qualitative platelet defects.

How does Multiple Myeloma cause renal disease? What are hematologic findings in Chronic Renal Failure?

What is Renal Osteodystrophy?

What are some complications of Renal Osteodystrophy? What are some cardiovascular findings in Chronic Renal Failure? What are some other clinical consequences of Chronic Renal Failure?

Chronic kidney disease-mineral bone disorder. Osteitis fibrosia cystica due to hypovitaminosis D. Causes hypocalcemia which then stimulates the production of PTH-secondary hyperparathyroidism. Hyperparathyroidism causes bone resorption causing cystic lesions in the bone. Hemorrhage into cysts caused brown discoloration. Osteomalacia from decreased mineralization of the osteoid. Osteoporosis from loss of organic bone mass and minerals (often due to chronic metabolic acidosis because excess H is buffered by bone minerals). Hypertension from salt retention, hemorrhagic fibrinous pericarditis, CHF and accelerated atherosclerosis. Hemorrhagic gastritis and uremic frost (urea crystals deposit on the skin). Also hyperkalemia and anion-gap metabolic acidosis. Hypovitaminosis D from decreased 1-Alpha Hydroxylase and thus decreased reabsorption of calcium from the small intestines. Also hyperphosphatemia from decreased renal excretion drives calcium into bone and soft tissue. Cystatin in a Cysteine protease inhibitor produces by the nucleus of all cells. It should be filtered by the glomerulus but not secreted so it's a good marker of renal function. Fixed specific gravity because no concentrating ability, free water clearance is 0, waxy/broad casts are present.

Why does renal failure cause hypocalcemia?

Why is there increased Serum Cystatin C? What is seen on urinalysis in Chronic Kidney Failure? Why do you give ACE inhibitors in kidney disease?

What is benign nephrosclerosis?

Reduce proteinuria and treat hypertension. Common renal disease in essential hypertension caused by hyaline arteriolosclerosis of arterioles in the renal cortex. Results in tubular atrophy, interstitial fibrosis and glomerular sclerosis. See small kidneys with a finely granular cortical surface.

What is Malignany Hypertension?

What microscopic changes are seen in Malignant Hypertension? What are clinical findings in Malignant Hypertension?

Sudden onset of accelerated hypertension with end organ damage. Risk factors are pre-existing BNS, Hemolytic Uremic syndrome, thrombotic thrombocytopenic purpura and systemic sclerosis Fibrinoid necrosis and necrotizing arteriolotis and glomerulitis with pinpoint hemorrhages on the cortical surface. Also hyperplastic arteriolosclerosis (onion skin lesions) with smooth muscle hyperplasia and reduplication of the basement membrane. Hypertensive encephalopathy-cerebral edema, papilledema, retinopathy with flame hemorhages and potential for an intracerebral bleed. Embolization from thrombi in the left heart, atheroembolic renal disease, vasculitis especially polyarteritis nodosa. Irregular wedge-shaped pale infarct in the renal cortex. Old infarct have a V shape from scar tissue. Complication of obstetric emergencies. Due to DIC in the renal cortex which results in fibrin clots in arterioles and glomerular capillaries and bilateral, diffuse, pale infarcts of the renal cortex. See anuria in a pregnant woman followed by ARF. Renal stones, retroperitoneal fibrosis, cervical cancer and BPH Compression atrophy of the renal medulla and cortex and dilated ureters and renal pelvis Hypercalcuria in the absence of hypercalcemia (absorptive hypercalcuria), decreased urine volume, reduced urine citrate (citrate chelates calcium), primary hyperparathyroidism, diet high in dairy (contains phosphates or oxalate), and urinary infections due to urease producers (proteus) Calcium oxalate stone-from vegans or people with Crohn's. Calcium Phosphate stone-dairy products and distal renal tubular acidosis.

What causes Renal infarction? What is the gross and microscopic appearance of a renal infarction?

What is Diffuse cortical necrosis? What are some causes of Hydronephrosis? What are some clinical findings of hydronephrosis?

What causes Urolithiasis?

What is a calcium stone?

What is a Magnesium Ammonium Phosphate stone? How do you treat a calcium stone? How do you treat a Uric Acid stone? How do you treat a struvite stone?

Struvite stone causing a Staghorn calculus. Associated with urease producing bugs. Urine is alkaline and smells like ammonia. Most pass. Can give hydrochlorothiazide which increases renal tubule reabsorption of calcium. Cellulose phosphate binds calcium in the intestine. Allopurinol, increase urinary pH to make the stone soluble. Cotreat chemo patients with allopurinol to prevent urate nephropathy. Surgical removal because of size. Antibiotic to eliminate urease producer. Hamartoma composed of blood vessels, smooth muscle and adipose cells. Associated with tuberous sclerosis causing mental retardation and multisystem hamartomas. Smoking, Von Hippel-Lindau, Adult PKD, obesity, asbestos and lead exposure, and gasoline or petroleum product exposure. AD disease with defect on chr 3. Increased VEGF causes hemangiobalstomas of the cerebellum and retina and bilateral renal cell carcinomas. Upper pole mass with cysts and hemorrhage composed of clear cells that contain lipids and glycogen. Tendency for renal vein invasion and invasion into the IVC and right heart. Hematuria, abdominal mass, flank pain, hypertension, triad of hematuria, abdominal mass and flank pain. Constitutional symptoms. Left sided variocele from blocking of left renal vein. EPO is elevated causing secondary polycythemia. PTH-related protein produces hypercalcemia. Transitional cell carcinoma. Risk factors are smoking, Phenacetin abuse, aromatic amines (aniline dyes), cyclophosphamide.

What is an Angiomyolipoma? What are risks for Renal Cell Carcinoma? What is Von Hippel Lindau disease? What are some gross and microscopic findings in Clear Cell renal carcinoma?

What are clinical signs of clear cell renal carcinoma? What hormonal changes are seen in renal clear cell carcinoma?

What is Renal Pelvic Cancer?

What is a Wilm's Tumor? Where do Wilm's tumors come from? How does a Wilm's tumor present?

AD tumor with the defect on chromosome 11. WAGR Syndrome-wilms tumor, aniridia (absent iris), genital abnormalities, retardation. Beckwith-Wiedmann syndromewilms tumor with enlarged body organs, hemihypertrophy of extremities. Large necrotic gray tumors derived from mesonephric mesoderm, containing abortive glomeruli and tubules with primitive blastemal cells and rhabdomyoblasts. Unilateral palpable mass in a child with hypertension (renin secretion). Metastasis to the lungs.