Case A 1. Gross Findings The gross morphologic appearance of a myocardial infarction can vary.

Patterns include: Transmural infarct - involving the entire thickness of the left ventricular wall from endocardium to epicardium, usually the anterior free wall and posterior free wall and septum with extension into the RV wall in 15-30%. Isolated infarcts of RV and right atrium are extremely rare. Subendocardial infarct - multifocal areas of necrosis confined to the inner 1/31/2 of the left ventricular wall. These do not show the same evolution of changes seen in a transmural MI. Gross morphologic changes evolve over time as follows: 0-12 hours--no macroscopic change 18-24 hours--pale or red (due to stagnated blood) 24-72 hours--pallor with hyperemic border 3-7 days--yellow color, soft, peripheral hyperemia weeks-months--pale gray scar

2 and 3. Slides and the Histologic Findings in slides Sequence of events macroscopic and microscopic appearances of the heart following an acute myocardial infarct Time post MI 0-12 hours Macroscopic appearance No changes. Histological appearance Normal. Separation of fibers and blurring of striations with some oedema. Loss of striations and nuclei (coagulative necrosis), infiltration by neutrophils and macrophages. Macrophages, lymphocytes and plasma cells present in a loose oedematous mesh. Fibroblast activity. Fibroblast activity well underway and granulation tissue formation. Tissue becomes more fibrous and forms a collagenous acellular scar.

12-24 hours Infarcted area appears pale. 24 hours-3 days 3 days-10 days 10 daysweeks Weeks months Necrotic muscle appears soft andyellowish. Ring of redness around necrotic muscle where healing is occuring. Area of healing larger and appears pink or gray. White fibrous scar.

This picture shows cardiac muscle 24 hrs after the onset of a myocardial infarct. There is coagulative necrosis of the muscle fibres; the cytoplasm appears homogenous and there is loss of nuclei. At high power (not shown), striations are lost.

This picture shows cardiac muscle 48 hrs after the onset of a myocardial infarct. The cardiac muscle fibres are necrotic. In addition, there is an acute inflammatory infiltrate of neutrophils between the muscle fibres.

Acute myocardial infarct, histology. This 3-4 day old infarct shows necrosis of myocardial cells and is infiltrated with PMN leukocytes. 4. Pathophysiology

5. Laboratory Exams

a. ECG (EKG) During the initial stage of the acute phase of MI, total occlusion of the infarct artery produces ST-segment elevation. Most patients initially presenting with ST-segment elevation evolve Q waves on theECG and are ultimately diagnosed as having sustained a Q-wave MI. A small proportion may sustain only a non-Q-wave MI. When the obstructing thrombus is not totally occlusive, obstruction is transient, or if a rich collateral network is present, no ST-segment elevation is seen. Such patients are initially considered to be experiencing either unstable anigna or a non-ST-segment elevation MI (NSTEMI). Among patients presenting without ST-segment elevation, if a serum cardiac marker is detected and no Q wave develops, the diagnosis of non-Qwave MI is ultimately made. A minority of patients who present initially without STsegment elevation may develop a Q-wave MI. Previously it was believed that transmural MI is present if the ECG demonstrates Q waves or loss of R waves, and nontransmural MI may be present if the ECG shows only transient ST-segment and Twave changes. However, electrocardiographic-pathologic correlations are far from perfect; and therefore a more rational nomenclature for designating electrocardiographic infarction is now commonly in use, with the terms Q-wave and non-Q-wave MI replacing the terms transmural and nontransmural MI, respectively.

b. Cardiac enzymes Certain proteins, called serum cardiac markers, are released into the blood in large quantities from necrotic heart muscle after AMI. The rate of liberation of specific proteins differs depending on their intracellular location and molecular weight, and the local blood and lymphatic flow. The temporal pattern of protein release is of diagnostic importance, but contemporary urgent reperfusion strategies necessitate making a decision (based largely on a combination of clinical and ECG findings) before the results of blood tests have returned from the central laboratory. Rapid whole-blood bedside assays for serum cardiac markers are now available and may facilitate management decisions, particularly in patients with nondiagnostic ECGs.

CKMB: The MB isoenzyme of creatine phosphokinase is more specific to AMI than CK. However, it may still be elevated in skeletal muscle injury. Rather than attempting to make the diagnosis ofAMI on the basis of a single measurement of CK and CKMB, clinicians should evaluate a series of measurements obtained over the first 24 h. Skeletal muscle release of CKMB typically produces a "plateau" pattern, whereas AMI produces aCKMB elevation that peaks approximately 20 h after the onset of coronary occlusion. When released into the circulation, the myocardial form of CKMB (CKMB2) is acted on by the enzyme carboxypeptidase, which cleaves a lysine residue from the carboxyl terminus to produce an isoform (CKMB1) with a different electrophoretic mobility. A CKMB2:CKMB1 ratio

of>1.5 is highly sensitive for the diagnosis of AMI, particularly 4 to 6 h after the onset of coronary occlusion. The MB-CK fraction appears in 4 hours after onset of infarction and peaks at about 24hrs with a duration of 72 hours. CK MB: 4h - 24h - 72h

Cardiac-specific troponin T (cTnT) and cardiac-specific troponin I (cTnI) have amino acid sequences different from those of the skeletal muscle forms of these proteins. These differences have permitted the development of quantitative assays for cTnT and cTnI with highly specific monoclonal antibodies. Since cTnT and cTnI are not normally detectable in the blood of healthy individuals but may increase afterAMI to levels over 20 times higher than the cutoff value (usually set only slightly above the noise level of the assay), the measurement of cTnT or cTnI is of considerable diagnostic usefulness, and they are now the preferred biochemical markers for MI. The cardiac troponins are particularly valuable when there is clinical suspicion of either skeletal muscle injury or a small MI that may be below the detection limit for CK and CKMBmeasurements. Levels of cTnI may remain elevated for 7 to 10 days after AMI, and cTnTlevels may remain elevated for up to 10 to 14 days. Thus, measurement of cTnT or cTnIhas replaced measurement of lactate dehydrogenase (LDH) and its isoenzymes in patients with suspected MI who come to medical attention more than 24 to 48 h after the onset of symptoms.

LDH on the other hand appears 12 hours after the infarct and peaks 2 days later to last 14 days. LDH has been largely replaced with the more specific cardiac troponin for patients with suspected AMI presenting after the initial 48 hours have passed.

c. Imaging Two-dimensional echocardiography (Chap. 227) is the most frequently employed imaging modality in patients with AMI. Abnormalities of wall motion are almost universally present. Several radionuclide imaging techniques are available for evaluating patients with suspected AMI. However, these imaging modalities are used less often than echocardiography because they are more cumbersome and they lack sensitivity and specificity in many clinical circumstances. Myocardial perfusion imaging with201Tl or99mTc-sestamibi, which are distributed in proportion to myocardial blood flow and concentrated by viable myocardium (Chap. 244) reveal a defect ("cold spot") in most patients during the first few hours after development of a transmural infarct. However, although perfusion scanning is extremely sensitive, it cannot distinguish acute infarcts from chronic scars and thus is not specific for the diagnosis of acute MI.

Case B 1. Gross Features Uterine prolapse is characterized under a more general classification called pelvic organ prolapse which encompasses descent of the anterior, middle and posterior structures into the vagina. Those organs that bulge anterior into the vagina are the urinary bladder which is called a cystocele, the urethra, which is called a urethrocele or a combination, which is a cystourethrocele. The uterus and the vaginal vault, which is the apex of the vagina, make up the organs that constitute the middle portion descent into the vagina. The vaginal vault often prolapses as a result of a hysterectomy. The rectal bulge is called a rectocele and a bulge of part of the intestine and peritoneum is called an enterocele, these make up the posterior portion of pelvic organ prolapse. The information from this point forward will focus on uterine prolapse.

Uterine prolapse is classified using a four part grading system: Grade 1: Descent of the uterus to above the hymen Grade 2: Descent of the uterus to the hymen Grade 3: Descent of the uterus beyond the hymen Grade 4: Total prolapse.

2. Histologic Features The most common pathology identified was leiomyoma followed by adenomyosis. Hysterectomies done for uterovaginal prolapse showed atrophic endometrium on histopathological examination. Other less frequent pathologies identified included endometrial hyperplasia, chronic endometritis and endometrial polyp. The pathologic examination confirmed the clinical diagnosis in all cases of leiomyoma, adenomyosis and endometrial polyps. This study confirms that benign pathologies are more common in hysterectomy specimens than their malignant counterparts. 3. Pathophysiology Normally, the uterus is held in place by the muscles and ligaments that make up the pelvic floor. Uterine prolapse occurs when the pelvic floor muscles and ligaments stretch, become damaged and weakened, so they can no longer support the pelvic organs, allowing the uterus to fall into the vagina. Prolapse can be incomplete or, in more severe cases, complete when the uterus slips and drops outside of the vagina. In 1996, a standardized terminology for the evaluation of pelvic organ prolapse (POP) was established by the International Continence Society, the American Urogynecologic Society, and the Society of Gynecologic Surgeons. That terminology

replaced terms as cystocele, rectocele, enterocele, and urethrovesical junctions with precise descriptions relating to specific anatomic landmarks. The first points are on the anterior vaginal wall and categorize anterior vaginal wall prolapse accordingly. Point (Aa) is a point located in the midline of the anterior wall 3 cm proximal to the urethral meatus and is roughly the location of the urethrovesical crease. Point (Ba) represents the most distal position of any part of the anterior vaginal wall. Point (C) represents either the most distal edge of the cervix or the leading edge of the vagina if a hysterectomy has been performed. Point (D) represents the location of the posterior fornix (pouch of Douglas) in a woman with a cervix. Point (Bp) is a point most distal of any part of the upper posterior vaginal wall, and point (Ap) is a point located in the midline of the posterior vaginal wall 3 cm proximal to the hymen. To record measurements, these points should be expressed in centimeters above or below the hymen. It is important for the examining individual to express the position and other circumstances of the examination (eg, straining or not, patient flat on table or in examining chair). Staging of Pelvic Floor Prolapse Using International Continence Society Terminology (POP Quantification)

Stage 0: No prolapse is demonstrated. Points Aa, Ap, Ba, and Bp are all at -3 cm and either point C or D is between total vaginal length -2 cm. Stage I: Criteria for stage 0 are not met, but the most distal portion of the prolapse is >1 cm above the level of the hymen. Stage II: The most distal portion of the prolapse is less or equal to 1 cm proximal or distal to the plane of the hymen. Stage III: The most distal portion of the prolapse is >1 cm below the plane of the hymen but protrudes no further than 2 cm less than the total vaginal length in centimeters. Stage IV: Essentially complete eversion of the total length of the lower genital tract.

Case C 1. Gross feature

Gross specimen of lung tissue showing lesions (grey) caused by tuberculosis (TB). This is a lung infection caused by Mycobacterium tuberculosis bacteria. The lesion (tubercle) has led to the breakdown of lung air sacs (alveoli), meaning the lungs are less capable of gaseous exchange. Symptoms include shortness of breath, coughing and fever. TB is an infectious disease which was once a major killer worldwide. Treatment involves a long course of antibiotic drugs.

Gross clinical specimen of a section through a lung in a tuberculosis (TB) infection. A TB infection results from inhaling Mycobacterium tuberculosis bacteria. Nodular lumps of damaged lung tissue and cavities result. TB causes coughing (often with bloody sputum), chest pain, shortness of breath and fever. It may be fatal. It can be treated with antibiotic drugs, although they may have to be taken for several months.

Classical apical cavitations with numerous caseating necrosis and massive tissue consolidation of lung parenchyme

The Ghon complex consists of the primary focus of infections, typically in the upper part of the lower lobe or the lower part of the upper lobe, combined with involvement of hilar lymph nodes.

2. Histologic Features Microscopically, the characteristic lesion in tuberculosis is the tuberculous granuloma.

Pulmonary tuberculosis. Tuberculous granuloma is localized in the pulmonary interstitium, compressing the surrounding alveoli and destroing the parenchyma. 3. Outcome if untreated The most serious outcome of untreated active tuberculosis isdeath. For those who survive, tuberculosis can cause extreme pain and very serious health problems. Here are some of the possible complications of untreated active tuberculosis:

Development of drug-resistant tuberculosis. Tuberculosis that goes untreated, or particularly tuberculosis that isn't properly treated with a thorough regimen of antibiotics, may mutate into a drug-resistant form of tuberculosis. Drug-resistant tuberculosis is much more difficult to treat, and treatment must go on for much longer often more than a year. Long-term damage to the lungs. Without treatment, tuberculosis bacteria can rapidly multiply and spread throughout the body. The bacteria can quickly infect the lungs and cause serious damage, such as a collapsed lung. Many people may also begin coughing up large amounts of blood if tuberculosis continues to damage the lungs. Organ damage. Untreated tuberculosis can spread beyond the lungs and into other organs, causing damage that can affect functioning. The liver is commonly affected by tuberculosis, resulting in serious damage and liver function problems. Joint damage. Tuberculosis bacteria, unless treated, can spread outside the lungs and even into the bones and joints. Bacteria in the joints can cause extreme pain, swelling, and even abscesses in, and damage to, the joints sometimes leading to arthritis.

Eye problems. When TB bacteria spread into the eyes, the result can be redness, irritation, and swelling of the retina and other parts of the eye.

4. LaboratoryExams a. Tuberculin skin test: The TB skin test (also called the Mantoux tuberculin skin test) is performed by injecting a small amount of fluid (called tuberculin) into the skin in the lower part of the arm. A person given the tuberculin skin test must return within 48 to 72 hours to have a trained health care worker look for a reaction on the arm. The health care worker will look for a raised, hard area or swelling, and if present, measure its size using a ruler. Redness by itself is not considered part of the reaction. The skin test result depends on the size of the raised, hard area or swelling. It also depends on the persons risk of being infected with TB bacteria and the progression to TB disease if infected.

Positive skin test: This means the persons body was infected with TB bacteria. Additional tests are needed to determine if the person has latent TB infection or TB disease. A health care worker will then provide treatment as needed. Negative skin test: This means the persons body did not react to the test, and that latent TB infection or TB disease is not likely.

b. TB blood tests: TB blood tests (also called interferon-gamma release assays or IGRAs) measure how the immune system reacts to the bacteria that cause TB. An IGRA measures how strong a persons immune system reacts to TB bacteria by testing the persons blood in a laboratory. Two IGRAs are approved by the U.S. Food and Drug Administration (FDA) and are available in the United States: 1. QuantiFERONTB Gold In-Tube test (QFT-GIT) 2. T-SPOT.TB test (T-Spot) Positive IGRA: This means that the person has been infected with TB bacteria. Additional tests are needed to determine if the person has latent TB infection or TB disease. A health care worker will then provide treatment as needed. Negative IGRA: This means that the persons blood did not react to the test and that latent TB infection or TB disease is not likely. IGRAs are the preferred method of TB infection testing for the following:

People who have received bacille CalmetteGurin (BCG). BCG is a vaccine for TB disease. People who have a difficult time returning for a second appointment to look for a reaction to the TST.

There is no problem with repeated IGRAs. c. Chest X-ray If you've had a positive skin test, your doctor is likely to order a chest X-ray. This may show white spots in your lungs where your immune system has walled off TB bacteria, or it may reveal changes in your lungs caused by active tuberculosis.

d. Sputum tests If your chest X-ray shows signs of tuberculosis, your doctor may take a sample of your sputum the mucus that comes up when you cough. The samples are tested for TB bacteria. These bacteria can also be tested to see if they are resistant to the effects of medications commonly used to treat tuberculosis. This helps your doctor choose the medications that are most likely to work.