Monthly Archives: June 2010

Toxemia of Pregnancy

Posted on June 30, 2010 by admin

Toxemia of Pregnancy

Clinical features

Toxemia of Pregnancy occurs in about 6% of pregnant women, usually in last trimester; more often in primiparas (woman who are for the first time pregnant) than multiparas. Some of these women become seriously ill, developing convulsions (eclampsia). These patients develop DIC with lesions in the brain, liver, kidney, placenta, and heart.

Symptoms of toxemia of pregnancy include:

- Hypertension
- Proteinuria
- Edema

Causes and pathology

Causes of toxemia of pregnancy include abnormal placentation leading to placental ischemia. May involve defects in placental trophoblastic invasion and development of physiological alterations in the placental vessels required to adequately perfuse the placental bed; thought to be due to immunologic and genetic factors. Leads to shallow implantation with incomplete conversion of decidual vessels to those needed for adequate placental perfusion.

May be due to intrinsic defect in invading trophoblast (inability of invading trophoblast to assume phenotype of normal endothelial cells). This leads to uterine vascular remodelling leading to placental ischemia. Induces production of vasoconstrictors (thromboxane, angiotensin, endothelin) and inhibition of vasodilators (NO, prostaglandins) within ischemic placenta leading to DIC, organ damage and hypertension. Hypertension may be due to fact that pregnant women with toxemia lose resistance to vasoconstrictive and hypertensive effects of angiotensin, due to decreased production of prostaglandin E by toxemic placenta. Renin production by toxemic placenta may also contribute to hypertension. Endothelial damage, primary platelet alteration and disruption in level and activities of coagulation factors may occur in toxaemia leading to DIC; toxemic placenta produces increased thromboplastic factors and reduced antithrombin III levels leading to procoagulant state.

Placenta Changes

- Placental infarcts
- Increased frequency of retroplacental hematomas
- Increased villous ischemia with formation of prominent syncytial knots, thickening of trophoblastic basement membrane, and villous hypovascularity
- Fibrinoid necrosis and acute atherosis of uterine vessels

Other organs affects:

- Liver
- Kidney
- Brain
- Heart
- Anterior pituitary

References:

Robbins Basic Pathology 7th ed, edited by Vinay Kumar, Ramzi S. Cotran, and Stanley J. Robbins, 873 pp, Philadelphia, Pa, Sounders, 2003.

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Apoptosis

Posted on June 29, 2010 by admin

Apoptosis

Apoptosis Definition

Apoptosis is programmed cell death. A molecular pathway of cell death that is tightly regulated by an intracellular program. Occurs physiologically (and in some instances pathologically) and serves to remove unwanted cells, cells that may be potentially harmful and those that have outlived their usefulness. In apoptosis, cell signals allow for cellular enzymatic breakdown of chromatin and cellular proteins within an intact cell membrane. The structural alteration marks the cell for phagocytosis by macrophages, bypassing an inflammatory host response

Difference between Apoptosis and Necrosis

Necrosis

Necrosis only occurs in pathological states and is characterized by loss of plasma membrane integrity, enzymatic destruction of cells and an inflammatory response.

Apoptosis Types

Physiologic  Apoptosis

- Embryogenesis
- Hormone-dependent involution in the adult
- Cell deletion in proliferating cell populations
- Death of host cells that have served their purpose (eg. neutrophils in inflammatory response; leukocytes after an immune response)
- Elimination of potentially harmful self-reactive T-lymphocytes
- Cell death induced by cytotoxic T-lymphocytes

Pathologic Apoptosis

- Cell death produced by a variety of injurious stimuli (eg. radiation, chemotherapy, heat, hypoxia, stress to endoplasmic reticulum)
- Cell injury in certain viral diseases (eg. viral hepatitis)
- Pathological atrophy in parenchymal organs after duct obstruction
- Cell death in tumors

Microsopic features

Apoptosis involves single cells or small clusters of cells. Apoptotic cell appears as a round or oval mass with intensely eosinophilic cytoplasm with dense nuclear chromatin fragments. No evidence of host inflammatory response.

Electron Microscopy

Cell shrinkage:

Cell is smaller in size, cytoplasm is dense and the organelles are more tightly packed

Chromatin condensation:

Chromatin aggregates peripherally under the nuclear membrane and the nucleus breaks up into two or more fragments

Formation of cytoplasmic blebs and apoptotic bodies:

Cytoplasm undergoes surface blebbing and then fragments into membrane-bound apoptotic bodies composed of cytoplasm and tightly packed organelles with or without nuclear fragments

Phagocytosis of apoptotic cells and bodies by macrophages:

Apoptotic bodies are taken up by macrophages where they are rapidly degraded within lysosomes.  Healthy cells migrate or proliferate to take up the space left by the apoptotic cell

Apoptosis Histology

1. cell shrinkage
2. chromatin condensation
3. cytoplasmic blebs and apoptotic bodies (cytoplasm with organelles and NO nuclear frags)
4. phagocytosis of apoptotic cells by macrophages

Biochemical features of apoptosis

1. protein cleavage
2. DNA fragmentation
3. phosphatidylserine residue expression on cell surface (phosphatidyl is “flipped out”)

Genes involved in apoptosis

1.    p53
2.    Fas-FasL
3.    TNF
4.    Bcl-2
5.    Caspases (Caspase-3)

Apoptotic Genes

Pro-apoptosis genes:

1.    p53
2.    Fas
3.    TNF
4.    cytochrome C

Anti-apoptotic genes:

1.    Bcl-2
2.    Bcl-x

Pathways involved in apoptosis

1. Extrinsic pathway (Fas, TNF-receptor)
2. Intrinsic pathway (mitochondrial:cytochrome c)
3. Execution phase (caspase 3, 6)
4. Removal of dead cells (macrophages)
References:

Robbins Basic Pathology 7th ed, edited by Vinay Kumar, Ramzi S. Cotran, and Stanley J. Robbins, 873 pp, Philadelphia, Pa, Sounders, 2003.

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Hepatitis C

Posted on June 29, 2010 by admin

Hepatitis C

What happens with untreated Hepatitis C?

Natural history of Hepatitis C.

Incubation period ranges from 2-26 weeks (mean 6-12 weeks). In symptomatic acute HCV infection, antibodies to HCV only detected in 50-70% of patients; otherwise antibodies seen in 3-6 weeks. Clinical course is milder than HBV infection; rare cases are severe. Patients with chronic hepatitis C have characteristic episodic elevations of serum aminotransferases with intervening normal or near-normal periods. 15% of acute cases resolve; 85% become chronic hepatitis (rare cases of fulminant hepatitis exist). Of the 85% of cases of chronic hepatitis, 80% are stable; 20% progress to cirrhosis and eventually hepatocellular carcinoma (approximately 10 years later). 50% of the cirrhotic cases remain stable, the other 50% of cases are fatal.

Microscopic features

- Lymphoid aggregates within portal tracts

- Focal sublobular regions of macrovesicular steatosis

- Bile duct epithelial cell proliferation

- Interface hepatitis

- Bridging inflammation and necrosis

- Fibrosis and cirrhosis

Most common mode of transmission of Hepatitis C in North America

- Intravenous drug use (60%)

- Sexual transmission (15%)

- Transfusions prior to 1991 (10%)

- Hemodialysis patients and healthcare workers (5%)

- Perinatal transmission (6% of infected mothers)

References:

Robbins Basic Pathology 7th ed, edited by Vinay Kumar, Ramzi S. Cotran, and Stanley J. Robbins, 873 pp, Philadelphia, Pa, Sounders, 2003.

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Medullary Carcinoma

Posted on June 29, 2010 by admin

Medullary Carcinoma of Thyroid

Medullary carcinoma of the thyroid originates from the C-cell (parafollicular cell) which generates calcitonin.

Medullary Carcinoma Appearance

Grossly, tumours are firm, pale-gray to tan and infiltrative; larger lesions may contain hemorrhage and necrosis. Sporadic tumours are solitary and unilateral, while familial tumours are multiple foci of tumour and bilateral.

Microscopic features

Polygonal to spindle-shaped cells with granular cytoplasm that form nests, trabeculae and even follicles; some tumours may contain smaller, more anaplastic cells. Nuclei of cells have a “salt-and-pepper” appearance. Cells separated by highly vascularised stroma and hyalinised collagen. Acellular amyloid deposits are found within stroma.

Electron Microscopy

Variable numbers of membrane-bound electron-dense granules within cytoplasm of neoplastic cells.

Predisposing factors

•    MEN2A and MEN2B syndromes
•    Familial medullary thyroid carcinoma
•    Mutations involve RET protooncogene
•    C-cell hyperplasia

References:

Robbins Basic Pathology 7th ed, edited by Vinay Kumar, Ramzi S. Cotran, and Stanley J. Robbins, 873 pp, Philadelphia, Pa, Sounders, 2003.

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Endometrial hyperplasia

Posted on June 29, 2010 by admin

Endometrial Hyperplasia

Classification of endometrial hyperplasia

Simple hyperplasia

-    Without atypia

-    With atypia

Complex hyperplasia

-    Without atypia

-    With atypia

Association of Endometrial Hyperplasia with Endometrial Carcinoma

Simple hyperplasia

- [5% of these are considered EIN (endometrial intraepithelial neoplasia)]

Simple hyperplasia uncommonly progresses to adenocarcinoma.More often reflect a response to persistent estrogen stimulatio. Frequently evolve to cystic atrophy where both stroma and epithelium become atrophic.

Complex hyperplasia

Complex hyperplasia without atypia (44% of these are considered EIN)

Atypical (simple or complex) (79% are considered EIN), with 20-30% progess to a pattern deemed morphologic adenocarcinoma.

References:

Robbins Basic Pathology 7th ed, edited by Vinay Kumar, Ramzi S. Cotran, and Stanley J. Robbins, 873 pp, Philadelphia, Pa, Sounders, 2003.

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Burkitt

Posted on June 29, 2010 by admin

Burkitt lymphoma

Burkitt Lymphoma Pathogenesis

Burkitt lymphoma is caused by the translocation of c-myc (on chromosome 8 ) to immunoglobulin gene locus allowing for upregulation of c-myc (increased transcription and translation). Translocation occurs to IgH locus t(8;14) or light chain locus t(2;8) or t(8;22). This is thought to occur during errors in class switching or during attempted V(D)J joining, or breaks generated during somatic hypermutation of Ig genes.

Additional mutation of p53, MDM, or p16 are needed for malignant transformation.

Burkitt Lymphoma Histology

Tissues involved by Burkitt lymphoma are effaced by a diffuse proliferation of intermediate-sized cells (10 to 25 um diameter; similar to nuclear size of benign macrophages within tumor), containing round or oval nuclei with coarse chromatin, several nucleoli, and a moderate amount of faintly basophilic to amphophilic cytoplasm. There is a high mitotic index and high rate of apoptotic cell death within the tumor. This is a requirement. Tingible body macrophages are diffusely scattered among the tumor cells imparting a “starry sky” appearance to the neoplasm.

Classification in the Working Formulation and the REAL classification

Working Formulation

- Classified under high grade lymphoma (small, noncleaved cells)

REAL Classification

-    Classified as peripheral B-cell neoplasm

References:

Robbins Basic Pathology 7th ed, edited by Vinay Kumar, Ramzi S. Cotran, and Stanley J. Robbins, 873 pp, Philadelphia, Pa, Sounders, 2003.

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Berry Aneurysm

Posted on June 29, 2010 by admin

Berry  Aneurysm

Most common locations of Berry Aneurysms:

·         Anterior cerebral artery (anterior communicating artery)

·         Middle cerebral artery

·         Internal carotid artery

Associated systemic conditions for Berry Aneurysms:

·         ADPCKD

·         Ehlers-Danlos syndrome (type IV)

·         Neurofibromatosis type 1

·         Marfan syndrome

·         Coarctation of aorta

·         Fibromuscular dysplasia of extracranial arteries

Predisposing factors for Berry Aneurysms:

-   Cigarette smoking and hypertension are

Berry Aneurysm Gross Features

Unruptured aneurysms are a thin-walled arterial outpouchings at branch points of the circle of Willis or a major vessel just beyond. Measure 2-3 mm and are shiny, bright red surface with thin, translucent wall. Atheromatous plaques, thrombosis, or calcification may be found in wall or lumen of aneurysm. Brownish discolouration of brain/meninges indicates previous hemorrhage. Rupture occurs at apex of sac with extravasation of blood to subarachnoid space, substance of brain, or both.

Histological Features of Berry Aneurysms:

Arterial wall adjacent to aneurysm shows intimal thickening and attenuation of media as it approaches the neck of the aneurysm. At the neck of the aneurysm the muscular wall and intimal elastic lamina stop short and are absent from the aneurysmal wall itself. The sac is made up of thickened, hyalinised intima. The adventitia covering the sac is continuous with that of the parent artery

References:

Robbins Basic Pathology 7th ed, edited by Vinay Kumar, Ramzi S. Cotran, and Stanley J. Robbins, 873 pp, Philadelphia, Pa, Sounders, 2003.

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Azelastine HCl ophthalmic

Posted on June 17, 2010 by admin

Azelastine HCl ophthalmic

Drug Name Azelastine HCl ophthalmic

Azelastine HCl ophthalmic Drug Category AZELASTINE – OPHTHALMIC

Azelastine HCl ophthalmic Drug Information

IMPORTANT NOTE: The following information is intended to supplement, not substitute for, the expertise and judgment of your physician, pharmacist or other healthcare professional. It should not be construed to indicate that use of the drug is safe, appropriate, or effective for you. Consult your healthcare professional before using this drug. AZELASTINE – OPHTHALMIC (azz-ELL-ust-een) COMMON BRAND NAME(S): Optivar USES: This medication is used to treat itching of the eyes caused by allergies (allergic conjunctivitis). HOW TO USE: This medication is used in the affected eye(s), usually twice daily; or as directed by your doctor. Remove contact lenses before applying the eye drop. Wait at least 10 minutes after using this medication before inserting contact lenses. To apply eye drops, wash your hands first. To avoid contamination, do not touch the dropper tip or let it touch your eye or any other surface. Tilt your head back, gaze upward and pull down the lower eyelid to make a pouch. Place the dropper directly over the eye and instill the prescribed number of drops. Look downward and gently close your eye for 1 to 2 minutes. Place one finger at the corner of the eye near the nose and apply gentle pressure. This will prevent the medication from draining away from the eye. Try not to blink and do not rub the eye. Do not rinse the dropper. Replace the dropper cap after use. If you are using another kind of eye medication (e.g., drops or ointments), wait at least five minutes before applying other medications. Use eye drops before eye ointments, to allow the eye drops to enter the eye. SIDE EFFECTS: Eye irritation or stinging, headaches, or bitter taste in the mouth may occur. If any of these effects persist or worsen, notify your doctor promptly. If you notice other effects not listed above, contact your doctor or pharmacist. PRECAUTIONS: Tell your doctor your medical history, including: allergies (especially drug allergies). If you wear contact lenses, consult your doctor about the use of contact lenses when the eyes are red or irritated. Because your vision may be temporarily blurred or decreased after using this medication, use caution driving or performing activities requiring clear vision. This medication should be used only when clearly needed during pregnancy. Discuss the risks and benefits with your doctor. It is not known whether this drug passes into breast milk. Because of the potential risk to the infant, breast-feeding while using this drug is not recommended. Consult your doctor before breast-feeding. DRUG INTERACTIONS: Tell your doctor of all prescription and nonprescription medication you may use, especially of: other eye medications. Do not start or stop any medicine without doctor or pharmacist approval. OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. This medicine may be harmful if swallowed. NOTES: Do not share this medication with others. MISSED DOSE: If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up. STORAGE: Store dropper bottle upright at room temperature between 36 and 77 degrees F (2 to 25 degrees C) away from light and moisture.

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Azelastine HCl nasal

Posted on June 17, 2010 by admin

Azelastine HCl nasal

Drug Name Azelastine HCl nasal

Azelastine HCl nasal Drug Category AZELASTINE NASAL

Azelastine HCl nasal Drug Information

IMPORTANT NOTE: The following information is intended to supplement, not substitute for, the expertise and judgment of your physician, pharmacist or other healthcare professional. It should not be construed to indicate that use of the drug is safe, appropriate, or effective for you. Consult your healthcare professional before using this drug. AZELASTINE NASAL (azz-ELL-us-teen) COMMON BRAND NAME(S): Astelin USES: This antihistamine medication is used to relieve symptoms related to seasonal allergies. HOW TO USE: Use exactly as directed in the illustrated instruction sheet within the package and follow directions on the prescription label. Alternate nostrils when giving yourself the medicine. The medicine usually begins working within 3 hours of use. SIDE EFFECTS: Generally the medication is well tolerated. Bitter taste, headache and drowsiness have occurred, as well as nasal burning, sneezing, and dry mouth. If these continue or are bothersome, notify your doctor. Very unlikely but report: palpitations, chest pain, anxiety, mental/mood changes, diarrhea, numbness and tingling of hands or feet, change in sense of smell, vision problems, inability to urinate, weight gain, muscle pain. An allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of an allergic reaction include: rash, itching, swelling, dizziness, trouble breathing. If you notice other effects not listed above, contact your doctor or pharmacist. PRECAUTIONS: Before using this drug, tell your doctor your medical history, especially of: allergies, kidney problems, liver problems, heart disease, high blood pressure. This medication should be used only when clearly needed during pregnancy. Discuss the risks and benefits with your doctor. It is not known whether this drug is excreted into human milk. Discuss the risks of breast-feeding with your doctor. Alcohol may intensify any drowsiness effect from this drug. DRUG INTERACTIONS: Tell your doctor of all nonprescription or prescription medication you may take, especially of: cimetidine, sleep medicines, sedatives, tranquilizers, drugs for anxiety, narcotic pain relievers, antidepressants or other psychiatric drugs (e.g., chlorpromazine, haloperidol), other antihistamines. Do not start or stop any medicine without doctor or pharmacist approval. OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. NOTES: Do not share this medication with anyone else. MISSED DOSE: If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not “double-up” the dose to catch up. STORAGE: Store at controlled room temperature between 68 and 77 degrees F (20-25 degrees C) away from sunlight and moisture. Protect from freezing. Keep the bottle upright with the pump tightly closed.

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Azelaic acid topical

Posted on June 17, 2010 by admin

Azelaic acid topical

Drug Name Azelaic acid topical

Azelaic acid topical Drug Category AZELAIC ACID GEL – TOPICAL

Azelaic acid topical Drug Information

IMPORTANT NOTE: The following information is intended to supplement, not substitute for, the expertise and judgment of your physician, pharmacist or other healthcare professional. It should not be construed to indicate that use of the drug is safe, appropriate, or effective for you. Consult your healthcare professional before using this drug. AZELAIC ACID GEL – TOPICAL (ay-zeh-LAY-ick acid) COMMON BRAND NAME(S): Finacea USES: This medication is used to treat a certain skin condition called rosacea. It helps to reduce the number of inflamed skin lesions. HOW TO USE: This medication is for use on the skin only. Clean the affected area with a mild soap or soap-free cleanser and pat dry. Apply a thin layer of medication usually twice daily; or use as directed by your doctor. Gently massage it into the affected area. Wash your hands well after using this medication. Make-up may be applied after the medication has dried. Avoid getting any of this medication in the eyes or inside the nose or mouth. If it does get in your eyes, wash your eyes immediately with plenty of water. Call your doctor if eye irritation persists. Do not use large amounts or apply this product more often than directed. Your condition will not clear faster, but the chance for side effects may be increased. Improvement is usually seen within four weeks. However, it may take several weeks of continued use before the full effects of this medication are seen. Do not apply any dressing or covering over the treated area unless you are instructed to do so by your doctor. SIDE EFFECTS: Burning, stinging, tingling or itching skin may occur during the first few weeks, but then subside as your body adjusts to this medication. Rarely, excessive facial hair growth may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly. This medication may infrequently cause abnormal changes in skin color (hypopigmentation). Dark-skinned individuals may notice a lightening in skin color. Consult your doctor or pharmacist for advice and report these changes if they occur. Tell your doctor immediately if any of these unlikely but serious side effects occur: worsening of cold sores or fever blisters (oral herpes). Tell your doctor immediately if any of these highly unlikely but very serious side effects occur: worsening of asthma symptoms (e.g., increased trouble breathing, increased use of quick-relief inhalers). An allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of an allergic reaction include: rash, persistent itching, swelling, dizziness, trouble breathing. If you notice other effects not listed above, contact your doctor or pharmacist. PRECAUTIONS: This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: an allergy to propylene glycol. Before using this medication, tell your doctor or pharmacist your medical history, especially of: asthma, repeat episodes of cold sores or fever blisters (oral herpes), any allergies. Avoid any foods or liquids that may bring on redness, flushing and blushing of the skin (e.g., spicy foods, alcohol, hot drinks). This medication should be used only when clearly needed during pregnancy. Discuss the risks and benefits with your doctor. This medication may pass into breast milk. Consult your doctor before breast-feeding. DRUG INTERACTIONS: Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription products you may use, especially of: other skin products. Avoid use of skin care products that can cause further irritation (e.g., alcohol-containing cleansers, tinctures, astringents, abrasives and peeling agents). Consult your doctor or pharmacist for details. Do not start or stop any medicine without doctor or pharmacist approval. OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. This medicine may be harmful if swallowed. NOTES: Do not share this medication with others. MISSED DOSE: If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up. STORAGE: Store at room temperature at 77 degrees F (25 degrees C) away from light and moisture. Brief storage between 59 to 86 degrees F (15-30 degrees C) is permitted. Do not store in the bathroom. Keep all medicines away from children and pets.

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