Final Topic List Flashcards
1
Q
Apoptosis
A
Apoptosis:
- Definition – ATP-dependent programed cell death
- No loss of membrane integrity, cellular contents do not leak out, no inflammatory reaction
- Defective apoptosis is seen in cancer
- Phases – Priming, Execution, Degradation, Phagocytosis
- Mechanism – Activation of Caspases pathway
- Intrinsic (mitochondrial)– internal stimulation. Major pathway
- DNA damage/ Misfolded proteins accumulation - ↑ p53 and mitochondrial Ca2+ leakage
- decreased hormonal stimulation – as seen in embryogenesis, menopause
- Extrinsic – external stimulation
- TNF Receptor Family (TNF-R and FAS)
- Immune cells - Cytotoxic T Cells
- Intrinsic (mitochondrial)– internal stimulation. Major pathway
- Morphologic appearance
- Cell shrinkage, Eosinophilic cytoplasm
- Chromatin condensation followed by fragmentation
- Membrane blebbing and phagocytosis of apoptotic bodies by macrophages
- Physiologic examples
- Hormonal stimulation- menstrual cycle, thymus in adults. Intrinsic
- Inflammatory cells that accomplished their purpose (after recovering). Extrinsic
- Pathologic examples
- DNA damage (radiation, cytotoxic drugs, temperature, hypoxia). Intrinsic
- Cell injury due to viral infection. Extrinsic
2
Q
Necrosis
A
- Definition – Unregulated death of large cell population, resulting from severe damage to cell membranes and loss of ion homeostasis
- Mechanism
- Plasma membrane damage -> cell undergoes enzymatic degradation and protein denaturation, intracellular components leak -> local inflammatory reaction
- Cell swelling due to inability to maintain ion and fluid homeostasis
- Nuclear Changes (Pyknosis, Karyorrhexis, Karyolysis) [shrinkage, fragmentation, fading]
- Causes – Always pathological, caused by exogenous injury
- Ischemia
- Physical trauma
- Radiation
- Biological – Infections
- Chemical injuries/ toxins
- Types – Coagulative, liquefactive, caseous, fat, fibrinoid, gangrenous
3
Q
Apoptosis vs Necrosis
A
4
Q
Liquefactive necrosis
A
- Definition – Characterized by digestion of the dead cells due to ischemia -> tissue transformed into liquid viscous mass
- Results from cellular destruction by hydrolytic enzymes
- Neutrophils release lysosomal enzymes that digest the tissue
- Morphology – Material is creamy yellow - presence of dead leukocytes (pus)
- Outcome
- Early – cellular debris and macrophages
- Later – cystic spaces and cavitation (brain). Neutrophils and cell debris seen with bacterial infection
- Examples
- Brain infarcts – Ischemic death of cells within the CNS
- Bacterial abscess – Accumulation of leukocytes and liberation of enzymes
- Pancreatic necrosis – Proteolytic enzymes liquefy pancreatic parenchyma
- Treatment – Surgically hard, washing and antibiotics
5
Q
Coagulative (Denaturative) necrosis
A
- Definition – The most common form of necrosis
- Usually results from ischemic injury (infarction) in most tissues (except brain, which is liquefactive)
- Common organs are heart, liver, kidney
- Pathogenesis – Ischemia → denaturation of cytoplasmic proteins
- Architecture of dead tissues is preserved for a span of at least some days
- Loss of nucleus is observed
- Outcome – Ultimately, necrotic cells are removed by phagocytosis of cellular debris by leukocytes and their enzymes → replaced by scar tissue
6
Q
Coagulative (Denaturative) and Liquefactive Necrosis
A
Coagulative Necrosis
- Definition – The most common form of necrosis
- Usually results from ischemic injury (infarction) in most tissues (except brain, which is liquefactive)
- Common organs are heart, liver, kidney
- Pathogenesis – Ischemia → denaturation of cytoplasmic proteins
- Architecture of dead tissues is preserved for a span of at least some days
- Outcome – Necrotic cells are removed by phagocytosis and replaced by scar tissue
Liquefactive necrosis
- Definition – Characterized by digestion of the dead cells due to ischemia -> tissue transformed into liquid viscous mass
- Results from cellular destruction by hydrolytic enzymes
- Morphology – Material is creamy yellow - presence of dead leukocytes (pus)
- Outcome - Cystic spaces and cavitation (brain).
- Neutrophils and cell debris seen with bacterial infection
- Examples
- Brain infarcts – Ischemic death of cells within the CNS
- Bacterial abscess – Accumulation of leukocytes and liberation of enzymes (infection)
7
Q
Dystrophic Calcification
***What is the practical use of dystrophic calcification for doctors***
A
- Definition – Abnormal deposition of crystalline calcium phosphate (calcium salts), in dying or necrotic tissues
- Localized – normal serum levels of calcium and phosphate
- For life
- Together with smaller amounts of iron, magnesium, and other minerals
- Phases:
- Initiation
- Intracellular initiation is in the mitochondria of dead or dying cells
- Extracellular initiation is in membrane-bound vesicles derived from degenerative or aging cells
- Propogation: (of crystal formation) -> depends on concentration of Ca2+ and PO4 and the prescence of inhibitors
- Initiation
- Examples
- Fat necrosis – saponification
- TB -> in areas of caseous necrosis (lungs and pericardium) and other granulomatous infections
- Aging/Damaged heart valves -> (important cause of aortic stenosis in elderly)
- Atheroma’s of advanced atherosclerosis
- Microcalcification in the breast(seen in mammography) → carcinoma
- *Psammoma body: seen in: papillary carcinoma of the thyroid, meningiomas, papillary serous carcinoma of the ovaries*
*** Used to check for pancreatic damage***
8
Q
Metastatic Calcification
A
- Definition – Precipitation of calcium phosphate in normal tissue due to hypercalcemia (serum calcium or serum phosphate which is elevated)
- Increased serum levels force calcium into tissues to precipitate as calcifications
- Systemic hypercalcemia secondary to some disturbance in calcium metabolism
- Mainly interstitial tissues in Stomach, Kidneys, Lungs, blood vessels
- Increased serum levels force calcium into tissues to precipitate as calcifications
- Causes of hypercalcemia
- Hyperparathyroidism - ↑ PTH (Parathyroid tumors/ ectopic secretion/adenocarcinoma)
- Bone destruction (Increased bone catabolism -> Leukemia, primary tumors/Metastasis, immobilization)
- Vit D disorders (Intoxication, Sarcoidosis)
- In children, hypervitaminosis D -> can take on the form of metastatic calcifications
- Chronic kidney disease / renal failure (Phosphate retention = secondary parahypothyroidism)
- Mainly Affects:
- Interstitial tissues of the gastric mucosa, kidneys, lungs, systemic arteries, pulmonary veins
- All of these tissues lose acid and therefore have an internal alkaline compartment that predisposes them to metastatic calcification
- Interstitial tissues of the gastric mucosa, kidneys, lungs, systemic arteries, pulmonary veins
9
Q
DCIS(Ductal carcinoma in situ) and Calcification
A
- Definition:
- calcification of necrotic debris or secretory material
- DCIS Constitutes:
- only 5% of breast cancers in unscreened populations
- up to 30% in screened populations
- largely because of the ability of mammography to detect calcifications
- Treatment:
- surgery and irradiation to eradicate the lesion
- prognosis is excellent, with greater than 97% long-term survival
- If untreated, DCIS progresses to invasive cancer in roughly one-third of cases, usually in the same breast and quadrant as the earlier DCIS
10
Q
Hypertrophy
A
- Definition:
- ↑ in size of cells; ↑ size of affected organ
- ↑ structural proteins and organelles = ↑ in size of cells
- Can be physiologic or pathologic
- ↑ in size of cells; ↑ size of affected organ
- Cause:
- ↑ functional demand or by stimulation by hormones & growth factors
- Examples:
- Uterine Hypertrophy
- Stimulated by estrogenic hormones acting on smooth muscle through estrogen receptors
- ↑ synthesis of smooth muscle proteins
- ↑ in cell size
- Stimulated by estrogenic hormones acting on smooth muscle through estrogen receptors
- Myocardial Hypertrophy
- Pathologic Hypertrophy:
- Cardiac enlargement that occurs with hypertension or aortic valve disease (constant stress on cells)
- If myocardium is subjected to ↓ blood flow (ischemia) due to an occluded coronary artery, the muscle cells may undergo injury
- Sustained cardiac hypertrophy often leads to cardiac failure
- Pathologic Hypertrophy:
- Uterine Hypertrophy
11
Q
Hyperplasia
A
- Definition:
- ↑ in # of cells in an organ/tissue in response to a stimulus
- Only take place if there tissue contains cells capable of dividing
- Can be physiologic or pathologic
- Result of growth-factor-driven proliferation of mature cells
- in some cases: ↑ output of new cells from tissue stem cells
- Pathologic Hyperplasia = dysplasia & cancer
- Examples:
- Endometrial hyperplasia:
- Abnormal endometrial gland proliferation usually caused by excess estrogen stimulation
- If exposed to progesterone over long periods of time will cause hyperplasia; can progress to endometrial carcinoma
- Endometrial hyperplasia:
12
Q
Endometrial Hyperplasia
A
- Definition:
- Abnormal endometrial gland proliferation usually caused by excess estrogen stimulation
- Causes:
- ↑Estrogen, ↓Progesterone → ↑Gland/Stroma ratio
- Risk Factors: (↑ Estrogen) [PROMO]
- PCOS/ Ovarian tumor
- Replacement Therapy
- Obesity
- Menopause
- Classification: (Simple/Complex) (W/ or W/out atypia)
- Simple:
- Gland Pleomorphism, cystic/mild hyperplasia
- not prominent mitoses
- increased stroma between glands
- Rarely progress to CA (1-3%)
- Complex:
- Irregular gland shape, Gland crowding, ↑Stratification
- Atypical:
- Correlates with the development/ concurring finding of endometrial carcinoma
- Increased risk: 20-50%
- epithelial lining is irregular
- Treatment:
- a hysterectomy in patients no longer desiring fertility
- in younger patients, treatment with high-dose progestins may be used in an attempt to preserve the uterus
- Non-Atypical Treatment: Progestin, Dilation & Curettage
- Simple:
13
Q
Metaplasia
A
- Definition:
- Reprogramming of stem cells -> replacement of one cell type by another that can adapt to a new stress.
- First step toward neoplasia
- Most commonly involves surface epithelium
- Metaplastic cells are better able to handle new stress
- “Reversible”; removal of stressor
- Can progress to dysplasia
- Example:
- Barrett Esophagus:
- Acid refluxes from stomach into lower esophagus; the change in stress;
- changes the epithelium of the lower esophagus into a columnar non-ciliated mucinous epithelium
- Acid refluxes from stomach into lower esophagus; the change in stress;
- Barrett Esophagus:
14
Q
Dysplasia
A
- Defintion:
- Disordered, precancerous, epithelial cell growth
- Reversible w/ removal of stressor
- If dysplasia persists -> becomes carcinoma (irreversible)
- Examples:
- Cervical dysplasia, actinic (solar) keratosis
- MOA:
- long-standing pathologic hyperplasia
- metaplasia
15
Q
Anaplasia
A
- Definition:
- Loss of structural and functional differentiation within a cell or group of cells.
- When anaplasia occurs in neoplastic cells they are far distinct from original cells. Complete change=malignant
- Morphology:
- Pleomorphism, Hyperchromatism, Nuclear enlargement, Mitosis abnormality
16
Q
Neoplasia
A
- Definition – Uncontrolled, disorderly proliferation of cells, grow more rapidly than normal cells or tissue. Caused by failure of regulation mechanism (proliferation and maturation) of cells.
- Resulting in a benign or malignant growth known as a neoplasm.
- Etiology
- Sporadic – Statistical (environmental, nutritional etc.)
- Familial – >3 cases in family, not associated with one specific gene
- Genetic – Associated with specific genes. High possibility for malignancy
- Common locations – Breast (woman)/prostate (men), skin, lungs
- Classification – Classified as either malignant or benign, based on their behavior
- Benign – “-oma”. Slow growth, well demarcated, no metastasis. Tend to be encapsulated
- Papilloma, Lipoma
- Malignant – “-sarcoma”, “-carcinoma”. Fast growth, less differentiated, metastasizes
- Colonic adenocarcinoma – epithelial origin
- Osteosarcoma – Bones
- Astrocytoma – Glial (CNS)
- Melanoma – Skin
- Lymphoma – Lymphatic
- Benign – “-oma”. Slow growth, well demarcated, no metastasis. Tend to be encapsulated
- Causes of death
- Cachexia – Excessive body weight loss. Accompanied by weakness, anorexia and anemia
- Secondary infection. Usually pneumonia
- Obliteration of vital organs/system by tumor
- Diagnosis – Physical, radiographic, laboratory/biopsy/autopsy
17
Q
Infarction
A
- Definition – Localized area of necrosis secondary to ischemia
- Causes
- 99% are due to thrombotic or embolic occlusion of blood vessels
- Less common- vasospasm or torsion
- Classification
- Anemic (Pale) infarcts – Pale or white color. Caused by thromboembolic events in solid organs with single blood supply- heart, kidney, spleen
- Hemorrhage (Red) infarcts – Red color. Occurs in:
- Venous occlusion – testicular/ovarian torsion
- Loose tissues – lung
- Tissues with dual circulations - lung and small intestine, liver, thyroid, uterus, testis, tongue, urinary Bladder
- Also occurs after reperfusion (after angioplasty)
- Complications – Coagulative necrosis (most organs) or liquefactive necrosis (brain) →inflammation and scarring
- Treatment – If necrosis → resection with healthy margins
18
Q
Hemorrhage
A
- Definition – Leakage of whole blood from its vessels
- Most often caused by trauma
- Classifications:
- Internal, External, Semi-external (bleeding in urinary bladder)
- Arterial (red, fast), Venous(purple, slow), Parenchymal (capillaries, small red dots on the skin)
- Types:
- Hematoma – Hemorrhage into a soft tissue/ organ → Hemosiderosis
- Petechiae – Pinpoint haemorrhages 1-2mm in diameter.
- Bleeding from small vessels into Skin, Mucosa, Serosa
- Causes – Coagulopathy (↓platelet/ defective function), ruptured vasculature
- Purpura – Diffuse superficial (skin), up to 1cm
- Causes – As above and trauma, vasculitis, increased vascular fragility
- Ecchymoses – Diffuse, Larger (1-2cm). skin and subcutaneous tissues
- Discoloration of the skin due to hemoglobin metabolism (Red-Blue) -> Biliverdin/Bilirubin(Blue-Green) -> Hemosiderin (Golden-Brown).
- May appear with coagulation disorders (Cushing syndrome)
19
Q
Edema
(Peripheral and Pulmonary)
A
Peripheral Edema
- Definition – Presence of excess fluid in interstitium
- Causes
- 1) ↑ Hydrostatic pressure in blood vessels - Congestive heart failure, portal HTN/cirrhosis, renal salt and water retention, venous thrombosis
- 2) ↓ Oncotic pressure - liver disease, nephrotic syndrome, and protein deficiency
- 3) Microvasculature
- Lymphatic obstruction - Inflammatory, Neoplastic, Postsurgical
- Increase endothelial permeability - inflammation, hypersensitivity reaction, some drugs
- Sodium retention - ↑intake, primary aldosteronism, renal failure
- Decompression disease - High mountain climbers
- Chemicals (weapons, industry)
- Classification
- Local – seen in inflammation
- Generalized – seen in heart Failure
- Anasarca – severe generalized edema
- Effusion- fluids within the body cavity. (e.g. pleural effusion)
- Types of edema fluid
- Transudate - low protein content
- Exudate - high protein content and cells
- Lymphedema - related to lymphatic obstruction
- Glycosaminoglycan-rich - ↑ hyaluronic acid and chondroitin sulfate → myxedema edema
Pulmonary Edema:
- Definition – Leakage of excessive interstitial fluid which accumulates in alveolar spaces
- Causes – Disruption of Starling forces or endothelial injury
- 1) ↑ hydrostatic pressure - seen in left-sided heart failure, mitral valve stenosis, and fluid overload.
- 2) ↓ oncotic pressure - seen in nephrotic syndrome and liver diseases
- 3) ↑ capillary permeability - due to infections, narcotics, shock, and radiation.
- Clinical manifestation
- Left Heart Failure -> Poor systemic perfusion, congestion of pulmonary circulation
- Wet and heavy lungs
- Presence of hemosiderin-laden macrophages (“heart failure” cells) in lungs
- Fibrosis in interstitium – Brown induration
- Left Heart Failure -> Poor systemic perfusion, congestion of pulmonary circulation
20
Q
Inflammation
A
- Definition – Response to eliminate initial cause of cell injury, to remove necrotic cells resulting from the original insult, and to initiate tissue repair.
- Consequence – Can cause considerable harm if prolonged, severe or inappropriate.
- Cardinal signs – Rubor (redness), Calor (heat), Dolor (pain), Tumor (swelling), Loss of function
- Causes – Infection, Trauma (Physical/ Chemical), Immunological injury, Tissue death (necrotic areas)
- Classifications
- Basic
- Acute- Neutrophils.
- Serous - protein poor. Transudation into body cavities. Seen in burns and viral infection.
- Purulent (suppurative)- edema, Pus – Exudate containing neutrophils→ abscess formation
- Fibrinous- ↑increase vascular permeability, ↑fibrin.
- Ulcer - Local defect/excavation of organ/tissue surface
- Subacute – Relatively rapid onset
- Chronic- Lymphocytes, Plasma cells. Simultaneous tissue destruction and repair
- Non-specific/granulomatous (Caseating- fungal. Non-Caseating- sarcoidosis, foreign material)
- Mixed
- Acute- Neutrophils.
- Basic
- Exudate - Serous, Purulent, Hemorrhagic (Ebola), or Fibrinous
- Superficial / Deep (Abscess – Deep)
- Limited / Diffused (Abscess – Limited)
- Specific (Crohn’s disease, ulcerative colitis)
21
Q
Acute Inflammation
A
- Definition – Immediate response with limited specificity (innate immunity)
- Rapid onset (seconds to minutes)
- Short duration (minutes to days)
- Causes - Infection, trauma, necrosis, foreign body
- Mechanism
- Vascular- vasodilation, ↑blood flow and endothelial permeability
- Cellular – Migration and extravasation of leukocytes and neutrophils
- Types
- Serous– Protein-poor fluid (transudation into body cavities e.g. peritoneum, pleura, pericardium). Seen in Burns, Viral Infection
- Fibrinous – ↑ Vascular Permeability, ↑Fibrin
- Suppurative (Purulent) – Edema, Pus – Exudate containing neutrophils→ abscess formation
- Ulcer – Local defect / excavation of organ/tissue surface
- Outcomes
- Resolution and healing (regeneration)
- Scarring – Substantial tissue destruction
- Abscess formation–pus (cavity filled with neutrophils and cellular debris walled by fibrous tissue)
- Chronic inflammation – Cause not removed
22
Q
Chronic Inflammation
A
- Definition – Prolonged inflammation characterized by mononuclear infiltration, which leads to simultaneous tissue destruction and repair (including angiogenesis and fibrosis).
- Causes
- May be preceded by acute inflammation
- Persistent infections – TB, syphilis (Treponema Pallidum)
- Immune-mediated – Hypersensitivity or autoimmune
- Toxins – Prolonged exposure to toxic agents (e.g. Silica) and foreign materials
- Mechanism
- Nonspecific inflammation – Mediated by macrophages and lymphocytes
- Granulomatous inflammation - Seen in fungal/ some bacterial infections
- Outcomes
- Scarring
- Amyloidosis
- Neoplastic transformation
23
Q
Acute vs Chronic Inflammation
A
24
Q
Granulomatous Inflammation
A
- Definition – A pattern of chronic inflammation
- Granulomas “wall off” a resistant stimulus without completely eradicating or degrading it → persistent inflammation→ fibrosis, organ damage
- Types
- Caseating - Associated with central necrosis. Caused by infectious agents:
- Bacterial: TB, listeria, T. pallidum
- Fungal
- Parasitic
- Non-caseating - No central necrosis. Seen in non-infectious disorders:
- Autoimmune diseases: Sarcoidosis, Crohn, thyroiditis
- Vasculitis: Wegener granulomatosis, giant cell arteritis
- Foreign material: berylliosis, talcosis, hypersensitivity pneumonitis
- Chronic granulomatous disease
- Caseating - Associated with central necrosis. Caused by infectious agents:
25
Q
Repair vs Regeneration
A
- Definition – A complex process in which the skin, and the tissues under it, repair themselves after injury
- Stages
- 1.Inflammatory phase (up to 3d after injury) - Clot formation, ↑ vessel permeability, neutrophil migration
- 2.Proliferative (day 3–weeks after injury) - Deposition of granulation tissue and type III collagen, angiogenesis, epithelial cell proliferation
- 3.Remodeling (1 week–6+ months after injury) of collagen to ↑ tensile strength of tissue
- Intentions
- Regeneration (Primary healing) – Replacement of dead cells by proliferation of cells of same type – involves cell growth & differentiation and cell-matrix reactions – requires intact basement membrane. Occurs with clean wounds with little tissue damage and adjacent surfaces closely together. Examples - Surgical suture, muscle fiber damage.
- Repair (Secondary healing) – Replacement of injured tissue w/fibrous scar, NOT w/parenchymatous tissue of same kind. Occurs in large tissue defect /Suture impossible / Intense inflammatory response -> Longer healing.
- Examples - Large surface ulcers and open wounds
- Interruptions
- Foreign body/material, Infection – continued tissue damage
- Ischemia, Diabetes, Obesity, Old age
- Malnutrition (Vit. C- scurvy, Zinc, water)
26
Q
Grading and Staging
A
- Most important indicator of prognosis and therapy of malignant tumor.
- Helps to calculate 5-year survival rate
- Grading
- Definition – Degree of cellular differentiation and mitotic activity of malignant tumor cells as seen on histology, relative to tissue of origin.
- Ranges from low grade (G1. well-differentiated) to high grade (G4. poorly differentiated, undifferentiated, or anaplastic)
- ↑ Grades -> ↑ Response to chemo/radiotherapy (but also more aggressive)
- Staging
- Definition – Clinical/pathological assessment of the degree of localization/spread of malignancy
- Advanced stage → Require agressive treatment
- Staging (TNM)
- T – Primary Tumor Size and Local extent (Depth, invasiveness level). T1-T4
- T0 -> in-situ lesion
- N – Regional lymph Node involvement. N0-2 (no nodes, local, distant)
- M – Metastases. M0,1 (No metastasis, yes metastasis)
- T – Primary Tumor Size and Local extent (Depth, invasiveness level). T1-T4
27
Q
5 Year Survival Rate
A
- % of people in a study or treatment group who are alive 5 yrs after they were diagnosed with or started treatment for a disease, such as cancer; survival rate for estimating the prognosis
- Normally calculated from point of diagnosis
- Not used in leukemia & lymphoma (upto 12 months survival)
- Depends on:
- Stage first diagnosed
- Treatment possibility
- Examples:
- Breast Cancer - 70%
- Osteosarcoma - 60%
- Leiomyosarcoma - 40%
- Lung Carcinoma - 10%
- Pancreas Carcinoma - 1.8%
- Hodgkin’s Lymphoma: 70-90%
28
Q
Metastasis
A
- Definition – The hallmark of cancer. Tumor cells that grow in one location, spread to a distant location and implanted there.
- Spreading routes:
- Local spread
- Vascular/lymphatic- most common
- CSF space- less common
- Contact seeding
- Abnormal cavities (pleural/peritoneal)
- Common sites of metastasis:
- Brain- 1 degree tumor is most common originating: Lung > breast > melanoma, colon, kidney.
- Liver- originating: Colon >> Stomach > Pancreas
- Bone- originating: Prostate, Breast > Kidney, Thyroid, Lung
29
Q
Carcinoma In-Situ/
(Grade 0, Preinvasive, Intraepithelial)
A
- Definition – Irreversible severe dysplasia that involves the entire thickness of epithelium but does not penetrate the intact basement membrane
- Represents the early stage of neoplasia, Pre-invasive Neoplasm
- The abnormal neoplastic cells grow in their normal place
- Synonyms:
- Grade 0
- Pre-invasive
- Intraepithelial
- Morphology – May share cytological features with malignancy
- Outcomes – Early detection and treatment usually successful
- Examples:
- Cervical Squamous-cell Carcinoma In-Situ
- Bronchioloalveolar carcinoma- the only form of CIS that can kill directly
30
Q
Oncogenic Viruses
A
- Viral Oncogenesis. ↑ oncogenes (gain of function) → Neoplasia
- HPV (subtypes 16, 18, 31, 33) → (SCC) of vulva, vagina, anus, cervix and (cervical adenocarcinoma)
- EBV → Burkitt/Hodgkin Lymphoma, nasopharyngeal carcinoma
- HBV, HCV → Hepatocellular Carcinoma (70-85% cases)
- HTLV-1/ Human T-lymphotropic virus -> Adult T-cell leukemia/ lymphoma
- HHV-8 (Human Herpes Virus) - Kaposi sarcoma
- Merkel Cell virus -> Merkel Cell carcinoma (very rare)
- H. Pylori -> Gastric Adenocarcinoma & Gastric Lymphomas (b cell origin)
31
Q
Benign Tumor
(Benign Neoplasia)
A
- Definition – Closely resemble tissue of origin (fully differentiated)
- Slow Growth
- Well demarcated – Margins well defined. Encapsulated
- No Metastases!
- Complications
- Compression of adjacent tissues
- Blockage of lumen
- Endocrine functions
- Examples “-oma”
- Lipoma- adipose tissue
- Fibroma- connective tissue
- Adenoma- glandular epithelium and their surrounding connective tissue.
- Papilloma- surface epithelium (skin, larynx, tongue)
- Non-neoplastic examples
- Choristoma- Growth of normal tissue in an abnormal location
- Hamartoma- disorganized, tumor-like overgrowth of cell types regularly found within an affected organ
32
Q
Malignant Tumor
A
- Definition – Neoplasm with tendency to become worse
- Grow fast
- Margins poorly defined - Not encapsulated
- Invasive and Metastasize (Through Lymph, Blood, Cavities)
- Classification
- Well-Differentiated – Constituent cells closely resemble tissue of origin
- Poorly-Differentiated – Little resemblance to tissue of origin
- More aggressive. Atypical cytology (cell features)
- Anaplastic – Impossible to identify cell of origin. The hallmark of malignancy
- Complications
- Invasiveness – Growth and destruction of adjacent tissues
- Metastasis – Cells from primary tumor become detached Migrate Grow as separate mass. Usually cause tissue destruction. Spreading routes
- Local spread, Vascular/lymphatic
- CSF space- less common. Contact seeding
- Abnormal cavities (pleura etc.)
- Treatment – Chemotherapy, Radiation, Surgery
- Examples – Sarcoma, Carcinoma, Teratoma
33
Q
Tumor Origin Names
A
- Mesenchymal -> Sarcoma
- Epithelial -> Carcinoma
- Glial -> Astrocytoma
- Skin -> Melanoma
- Lymphatic -> Lymphoma
34
Q
Atelectasis
A
- Definition – An area of collapsed or non-expanded lung (reduced volume of lung tissue).
- It is reversible, but areas of atelectasis predispose for infection due to decreased mucociliary clearance.
- Risk – Bedridden patients
- Types
- Obstruction/resorption - Airway obstruction prevents new air from reaching distal airways; examples include foreign body, COPD, mucus plug, and tumor
- Compression - External compression on lung→↓lung volumes: fluid/ blood, air, tumor in the pleural space.
- Can caused by car accident (→pneumothorax, blood, etc.)
- Mediastinum shift- if on one side only
- Contraction (scar) - Due to fibrosis and scarring of the lung.
- Adhesive (patchy) - Due to a lack of surfactant (not loss of it!), seen in NRDS in premature babies and ARDS in adults.
35
Q
Emphysema
A
- Definition – Destruction of alveolar septa results in enlarged air spaces (↓gas exchange area) and a loss of elastic recoil.
- Causes - Smoking, α1-AT deficiency (congenital/smoking), artificial ventilation, coal mining, diving
- Symptoms – Dyspnea, barrel chest, cyanosis, hypercapnia and respiratory acidosis.
- A characteristic tripod sitting posture
- Hyper-resonant percussion notes; diminished breath sounds on auscultation
- Types – By anatomical distribution of the septal damage:
- Centriacinar (Centrilobular)- The most common form. Damaged and dilated respiratory bronchioles. Caused by smoking/air pollution → chronic bronchitis and inflammation. Seen in upper lobes. Apical blebs and bullae may be seen.
- Panacinar (Panlobular)- Affects the entire acinus. Caused by α1-antitrypsin deficiency. Seen at the lower lobes.
- Paraseptal (Distal acinar)- Unknown cause. Extension to the pleura causes pneumothorax, fibrosis, scarring and atelectasis.
- Irregular- post-inflammatory scarring involves the acinus in an irregular distribution.
- Complications – Chronic bronchitis, Pneumothorax, Cor Pulmonale, right heart failure
36
Q
Lung Malignancies
A
- Epidemiology – The leading cause of cancer death
- 5 Year Survival – 10%
- Etiologies
- Tobacco smoking
- Industrial hazards [Coal, Uranium, Radiation, Asbestos, Arsenic, and Mustard gas
- Air Pollution – Radon
- Genetic factors – ↓Tumor Suppressor Genes
- Scarring – Adenocarcinomas
- Classification
- Adenocarcinoma(38%)-invasive with glandular differentiation. Women, non-smokers. Periphery. Good prognosis
- Preceded by Atypical adenomatous hyperplasia > Adenocarcinoma in situ
- Patterns: Acinar, Lepidic, Papillary/ Micropapillary, Solid
- Squamous cell carcinoma (20%) – Men, smoker. Centrally- main bronchi/entire lobe. Grows fast, metastasize late
- Progresses from metaplasia →CIS→invasive CA.
- Paraneoplastic syndrome may occur.
- Small Cell (Oat Cell) Carcinoma (14%)- Prognosis – 6 months. Males, smokers. Late diagnosis. Center/periphery.
- Paraneoplastic syndrome very common.
- Large Cell Carcinoma (3%). Smoking! Diagnosis by exclusion other types. Periphery, poor prognosis
- Mesothelioma – Rare, arise from mesothelium layer that covers the lung/many internal organs. Poor prognosis
- Asbestos exposure 90% of cases (latent period of 15-20years). Not associated w/smoking!!! Causes lung fibrosis, recurrent pleural effusions and may compress the lungs
- Adenocarcinoma(38%)-invasive with glandular differentiation. Women, non-smokers. Periphery. Good prognosis
37
Q
Lobar Pneumonia
A
- Definition – Consolidation of the entire lobe (usually the lower [LOWbar]) or the whole lung.
- Characterized by acute inflammatory intra-alveolar exudate
- More often in adults
- Causative organisms
- Strep Pneumonia- most frequently. Community acquired
- Klebsiella – Alcoholics
- Legionella (<5%)
- Haemophilus Influenza – Children, Elderly (60+), COPD
- Mycobacterium Tuberculosis
- Stages (Congestion -> Red Hepatization -> Gray Hepatization -> Resolution)
- Congestion – Vascular hyperemia, intra-alveolar fluid and edema
- Red Hepatization - Most people die here
- Neutrophils, RBCs and fibrin filling the alveolar spaces
- Liver-like consistency of lobe – Firm and airless
- Grey Hepatization - Progressive disintegration of RBC
- Resolution- Healing. Exudate is coughed up, digested or ingested
- Signs and Symptoms
- Fever, Cough, Dyspnea, Malaise
- Chest pain and Hemoptysis
- Radiology – Lobar alveolar filling
38
Q
Tuberculosis
A
- Definition – Chronic granulomatous inflammation caused by Mycobacterium Tuberculosis
- Location – Most common is lungs (Through sputum and inhalation). Also can be in GI
- Symptoms - Fever, Night sweat, Weight loss, Chronic cough, Hemoptysis
- Types
- Primary TB - Initial infection (in non-sensitized host), Lower lobes.
- Caseous granulomas with central necrosis.
- 95% will be fibrotic and calcified
- Characterized by Ghon complex
- Secondary TB - Activation of a prior Ghon complex (in sensitized host)/exogenous. Upper lobes
- Fibrocaseous cavitary lesions → localized destructive. Highly infectious
- Miliary TB - Secondary complicated. Spread to a new pulmonary or extrapulmonary sites (GIT, liver, adrenal gland, joints, bones)
- Primary TB - Initial infection (in non-sensitized host), Lower lobes.
- Diagnosis – PPD (skin test), Chest X-Ray
- Treatment – RIPE (Rifampin, Isoniazid, Pyrazinamide, Ethambutol).
- BCG Vaccination - not 100% efficient
51
Q
Hyperemia vs Congestion
A
80
Q
Crohn’s Disease VS Ulcerative Colitis
A
89
Q
Fibrocystic Changes VS. Proliferative diseases
A
