- When cell comes in contact with a stressor or a state of increased demand

- Cell will adapt if it can

- If cell can't adapt it will undergo cell injury and ultimately cell death

- If stressor is too large, adaptation will not even attempt to occur and cell will simply die

- Increased number of cells --> Increased volume of organ

- Only possible in cell populations that are capable of division

- Can be caused by either physiological or pathological stressors

- Example of physiological hyperplasia

- Occurs following the partial removal of the liver due to transplantation or injury

- Example of pathological hyperplasia

- Occurs as a result of testosterone stimulus

- Stromal hyperplasia

- Levels of 5 Alpha-reductase type 2 increase with age

- This results in increased levels of DHT

- DHT then binds to androgen receptors on the surface of nucleus

- Increased transcription of growth factors

- Growth factors cause hyperplasia

- Treatment: Finasteride --> Inhibits 5 Alpha-reductase type 2

- Increase in cell size --> Increased volume of organ

- Can occur in fully mature non-dividing cells

- Usually is caused by an increase in functional demand

- Can either be caused by physiological or pathological stressors

- Physiological hypertrophy

- Caused by an increased demand to detoxify the blood either from drugs or toxins

- Necessary to produce more of the P450 enzyme

- Pathological hypertrophy

- Caused by an increase in peripheral resistance~hypertension

- Caused by an increase in the load put on the cardiac muscle

- Most commonly left ventricular hypertrophy

- If hypertrophy is too extensive then heart cannot properly pump to perfuse itself

- Loss of cell sustance and/or cell number

- Occurs when protein degradation exceeds synthesis

- Often due to an increase in the ubiquitination process

- Autophagic vacuoles increase --> These vacuoles normally help degrade proteins

- Residual bodies increase

- Residual bodies are packages of lypofusion (remnants of proteosome)

- Atrophy of disuse

- Denervation atrophy

- Ischemia

- Inadequate nutrition

- Loss of hormonal stimulation

- Senile atrophy

- One cell type becomes another cell type

- Reversible --> Will reverse once stimulus is removed

- Induced by cytokines and growth factors in response to stress or injury

- Affects the tissue and the circulating stem cells

- Physiological metaplasia

- Stratified squamous non-keratinized --> Simple columnar

- Due to the exposure of the lower esophagus to the acidic environment in the stomach

- Problamatic because this is a pre-cancerous epithelial type

1. Aerobic respiration --> Production of ATP

2. Osmotic and ionic balance --> Membrane ion channels

3. Protein synthesis --> Ribosomes

4. Structural maintenance --> Cytoskeleton

5. Functional genetic apparatus --> Integrity of nucleus

1. Oxygen deprivation (hypoxia)

2. Physical agents --> Trauma

3. Chemical agents and drugs

4. Infectious agents

5. Immunologic reactions --> Oxidative bursts, etc

6. Genetic derangements

7. Nutritional imbalances

- Swelling: Due to ion channel abnormalities in the plasma membrane, mitochondria and ER --> Lets in water but membrane still intact

- Chromatin clumps but nucleus still intact

- Infiltration of lipid droplets into cells also occurs

- All reversible

- Chaotic process of cell death due to severe injury

- Cell membranes rupture

- Immune response results

- Nucleus breaks down

- Seen in an acute myocardial infarct

- Cell membrane outline is maintained

- No nuclei present in cells

- Infiltration of leukocytes

- Often seen in extremities and GI tract

- Black color due to the reaction of heme with oxygen when RBCs and other heme containing cells undergo necrosis

- Occurs when bacteria release hydrolytic enzymes

- Cell membranes are broken and fluid leaks out into the ECM

- No cellular outline --> Abcess forms

- Occurs only in the brain

- Specifically due to TB infection

- Forms a "cheesy" appearance

- Cells are faintly outlined

- Produced by the leakage of pancreatic enzymes into ECM

- Enzymes primarily act on fat

- Release of fatty acids from the tissue causes chalky calcium deposits (soaps)

- Usually seen with immune reactions involving blood vessels

- Antigens, antibodies and fibrin combine to form a fibrinoid

- Fibrinoid replaces the vessel wall in this case

1. ATP depletion --> Loss of energy/fuel

2. Entry of Ca2+ into the cell --> Activates apoptosis

3. Free radical production --> Causes protein and membrane breakdown through peroxidation

4. Membrane injury

5. Damage to DNA & proteins

- Programmed cell death --> Closely controlled

- No membrane breakdown --> No immune response results

- Only occurs to scattered individual cells

- Mostly a physiological process instead of pathological

- Activation of caspases --> Denature cytoplasmic proteins and cytoskeletal proteins

- Caspases --> Activate DNAases that digest DNA

- Cell is ultimately converted into multiple membrane bound vesicles that are quickly phagocytosed by macrophages

1. Extrinsic Pathway: Death ligands (on T-cells) bind death receptors

- TNF-1 receptor and FAS ligand --> FADD activation --> Binds pro-caspase 8 --> caspase 8 activation --> Apoptosis

2. Intrinsic/Mitochondrial Pathway: Anti-apoptotic proteins replaced with apoptotic proteins in mitochondria

- Increased mitochondrial membrane permeability --> cytochrome C release --> Binds Apaf-1 --> Activates caspase 9 --> Apoptosis

1. Organogenesis

2. Hormone-dependent involution

3. Cell deletion in proliferating cell populations

4. Death of neutrophils

5. Elimination of self-reactive lymphocytes

1. Viral diseases

2. Pathological atrophy following obstruction

3. Cell death in some tumors

4. Cell death in response to DNA injury

- Initially immune response

- Results in either complete regeneration of epithelium or fibrosis formation

- Regeneration ability depends on the epithelium type

- Labile Cells: Continuously dividing cells (surface epithelia)

- Stable Cells: Infrequently dividing cells (hepatocytes)

- Permanent Cells: Rarely or non-dividing (Neurons and skeletal muscle cells)

- Embryonic stem cells --> Totipotent

- Adult stem cells --> Pluripotent or multipotent

- Reside in niches that are generally located close to the proliferation zones of the tissue

- Baseline stem cell population --> Proliferates and then differentiates

- Divides assymmetrically --> One daughter cell stays in stem cell population while the other differentiates

- Regeneration by first intention --> Complete regeneration without scar formation

- Healing by second intention --> Scarring and wound conraction

- Local factors: Blood supply, denervation, infection, foreign body, necrotic tissue, mechanical stress, surgical technique, type and location of tissue

- Systemic factors: Diabetes, malnutrition, steroids, uremia, hypoxia, vitamin C deficiency, and malignant disease

- Layer I: Layer of dead cells and inflammatory response (neutrophils and fibrin) 

- Layer II: Granulation tissue --> Angiogenesis and neutrophils --> Re-establishes epithelium continuity

- Layer III: Extracellular matrix deposition and granulation tissue

- Layer IV: Remodeled ECM and fibrous scar

- Acute inflammation and necrosis

- Tissue elements: Fibrin, neutrophils, macrophages, and platelets

- Cytokines: Interleukins, interferons and TNF

- Growth Factors: PDGF and FGF

- Cell proliferation and migration

- Granulation tissue

- Angiogenesis is prominent

- Cellular elements: Capillaries, fibroblasts and macrophages

- Cytokines: TGF-B and angiopoietins

- Growth Factors: EGF/TGF-A, PDGF, FGF, and VEGF

- Usually takes more than 24 hours to produce (couple days after injury) --> Shows up later than 3 days in the heart

- Basal membrane: Collagen Type IV and laminin

- Interstitial matrix: Collagen type I, type III and fibronectin

- Fibrous proteins --> Collagens and elastins

- Cell adhesion proteins --> Cadherins, integrins, fibronectin, and laminin

- Gel of proteoglycans and hyaluronan

- Tissue texture --> Turgor, elasticity, and rigidity

- Reservoir for growth factors

- Substratum/matrix --> Responsible for cell adherence and migration

- Production of ECM

- Higher proportion of elastin than completely formed ECM

- ECM remodeling and scar formation --> Metalloproteinases, gelatinases and stromolysins

- Wound contraction --> Performed by myofibroblasts

- Regression of blood vessels

- Macrophages and monocytes

- Microglia (CNS)

- Histiocytes (CT)

- Kupffer cells (Liver)

- Host's response to injury or insult

- Caused by infections, trauma, loss of blood, vaccinations

- Immune reaction with blood flow

- Lasts hours to days

- Hallmark cell is the neutrophil --> Stays around until about day 4

- Cell derived mediators: storage granules or de novo synthesis

- Plasma Protein Derived: Proteins already present in plasma, produced by liver

- Stimulate other cells --> Release secondary effector molecules and amplify or oppose given response

- Quickly destroyed --> Half life very short

1. Vasodilation to increase flow

2. Microvascular changes allowing proteins and cells to leave the blood vessel

3. Emigration, accumulation, and activation of leukocytes 

- Performed by vasodilators

1. Vasoactive amines --> Histamine and serotonin

2. Cyclooxygenase products from arachinodic acid --> Prosaglandins and leukotrienes

3. Nitric oxide (NO)

4. Bradykinin

5. Platelet activating factor (PAF)

- Earliest mediators in response

- Pre-formed in cytoplasmic granules

- Released from mast cells and platelets

- Stimuli for release: Trauma, cold/heat, antibody binding, compement fragments (C3a and C5a), and neuropeptides (substance P)

- Action: Dilates arterioles and increases vascular permeability

- Vasodilators and increase vascular permeability

- Derived from arachindonic acid --> From phospholipids --> 20 carbon polyunsaturated fatty acid

- Produces prostaglandins, leukotrienes, and lipoxins

- Produced by cyclooxygenase reactions

- Production is inhibited by NSAIDs

- Derived from phospholipids

- Released from leukocytes, mast cells, endothelial cells and platelets

- Effects: Platelet aggregation, vasodilation at low levels, vasoconstriction at high levels, bronchoconstriction, leukocyte activation (oxidative burst), and leukocyte adhesion, chemotaxis and degranulation

- Synthesized from L-arginine and oxygen

- Exists in constitutive, inducible and endothelial forms

- Effects: Vasodilation, inhibition of cellular componenets and microbicidal

- Pre-kallikrein --> Kallikrein via Factor XIIa

- Kallikrein produces bradykinin from HMWK

- Effects: Increased vascular permeability, contraction of non-vascular smooth muscle, dilation of blood vessels and pain

- Fluid that passes due to hydrodynamic forces or the early inflammatory phase

- Specific gravity <1.015

- Low protein and cell content

- Clear fluid

- Fluid escaped from vasculature as a result of inflammation

- Specific gravity >1.015

- High protein and cell content

- Cloud appearance

- Implies some sort of immune reaction --> Usually due to an infection

- Effusion: Escape of fluid into a defined cavity --> Can be aspirated

- Edema: Escape of fluid into interstitium --> Cannot be aspirated

- Both can be either transudate or exudate fluid

- Serous: Contains few cells --> Clear fluid (mild injury)

- Purulent: Cloudy, high leukocyte content

- Hemorrhagic: Contains RBCs --> Capillary damage

- Fibrinous: Exudate with a layer of fibrin deposited on the serosal surface

- Due to retraction of endothelial cells

- Histamine

- Leukotrienes

- Nitric oxide

- Bradykinin

- Substance P

- Indicates more severe injury

- Cytokines

- Bacterial toxins

- Leukocytes

1. Margination due to vasodilation and decrease blood flow velocity

2. Rolling Adhesion --> Due to selectins on endothelial cells and integrins on leukocytes

3. Tight Adhesion --> Integrins on leukocytes

4. Diapedesis

- P-selectin on ECs --> Binds Sialyl-Lewis X on PMNs, monocytes and T-cells

- E-selectin on ECs --> Binds Sialyl-Lewis X on PMNs, monocytes, and T-cells

- Glycam-1 on ECs --> Binds L-selectin on PMNs and monocytes

- E-selectin on ECs --> Binds Sialyl-Lewis X on PMNs, monocytes, and T-cells

- ICAM-1 on ECs --> Binds CD11/CD18 integrins on PMNs, monocytes, and lymphocytes

- VCAM-1 on ECs --> Binds VLA-4 integrins on Eosinophils, monocytes, and lymphocytes

- Specific bacterial products

- Complement fragments (C5a)

- LTB4

- IL-8

- PAF

- C3a and C5a --> Stimulate histamine release from mast cells --> vasodilation and increased vascular permeability

- C5a --> Chemotaxis for neutrophils and activation of lipoxygenase pathway of arachidonic acid

- C3b --> Opsonizes bacteria

- Fever: Induced by TNF, IL-1 and IL-6 --> Release prostaglandins that act on the thermoregulatory center of the hypothalamus

- Leukocytosis: Caused by colony stimulating factors

- Tachycardia

- Tachypnea

- Acute Phase Proteins: Produced in liver due to IL-6 release by Kupffer cells

1. Intracellular killing: Phagocytosis --> Phagolysosome formation and oxidative burst

2. Extracellular Traps: DNA protein remnant of dying neutrophil --> Have antimicrobial activity

- Persists for more than a few days

- Causes: Prolonged exposure to injury/irritants, autoimmune diseases, and persistent infections

- Hallmarks: All leukocytes without neutrophils and with fibroblast involvement

- Same mediators as acute inflammation except without the granular release (histamine and serotonin)

- M1 --> Classically activated (acute): IL-1, IL-12, IL-23, ROS, NO and lysosomal enzymes

- M2 --> Alternatively activated (chronic): IL-10, TGF-B, arginase, and proline polyaminases

- M2 macrophages are involved in wound repair and fibrosis too

- Thicker tissue layer with WBC infiltration

- Activated macrophage --> Activates T-cell --> Further activation of macrophages, neutrophils and lymphocytes

- Activation via TNF and IL-17

- Important in both acute and chronic inflammation

- Released by macrophages/monocytes

- Keeps granulomatous inflammation going too

- Local concentrations are higher than systemic

- Half life of 10 minutes

- Effects: Activates leukocytes and platelets, increases leukocyte adhesion molecule expression, increases cytokine production, stimulates replication and activation of fibroblasts, and systemic symptoms of inflammation

- Overlapping functions as TNF

- Local concentrations higher

- Half-life of 10 minutes

- Also released by macrophages/monocytes

- Crucial treatment for autoimmune diseases such as RA, crohn's, psoriatic arthritis, ankylosing spondylitis, etc

- 4 different antibodies available

- Can reactivate dormant TB infections by stopping granulomatous inflammation

- Production: Kupffer cells, other macrophages, fibroblasts, endothelial cells, and activated T-cells

- Effects: Stimulates synthesis of acute phase proteins, causes fever, and stimulates growth of antibody-producing B-cells

- Alpha 1 Anti-trypsin (2-3x)

- Alpha 1 Anti-chymotrypsin (2-5x)

- Haptoglobin (1-2x)

- Fibrinogen

- C3

- C-Reactive Protein (5-500x)

- Hemopexin

- Serum Amyloid A Protein

- CRP and ESR tests used to determine state of inflammation

- State of chronic inflammation with periods of exacerbation

- Primarily due to eosinophil activation and histamine release

- Bronchi become filled with mucus secreted by the hypertrophied epithelium

- Eosinophils can be seen in peribronchial inflammation

- Characterized by an aggregate of epitheliod macrophages surrounded by a collar of lymphocytes

- Only associated with some pathologies

- Occurs when the body encounters a pathogen/insult that is too big for one cell alone

- Granuloma consists of macrophages, lymphocytes, fibroblasts and giant cells

- Begins with an antigen presenting cell that activates a CD4 Th1 cell via IL-12

- Th1 cell then produces TNF, IL-2, and IFN-gamma

- TNF is crucial to maintain granulomatous inflammation response

- Infections: Mycobacteria, coccidiomycosis, blastomycosis, spirochetes, etc

- Foreign body --> Suture

- Sarcoidosis

- Crohn's Disease

- Wegener's granulomatosis --> Necrotizing vasculitis

- Chronic granulomatous disease --> Inherited deficiency of NADPH oxidase

- Results in the accumulation of insoluble or inert substances/metabolites within lysosomes

- Due to deficiency of a lysosomal enzyme

- Distribution of stored material is determined by the site where most of the material to be degraded is found and the location where degradation normally occurs

- Breakdown lipids and glycogen products

- Can work on endogenous products (autophagy) or exogenous products (heterophagy)

- Lysosomal enzymes produced in the RER and transported to the vacuoles via the golgi

1. Sphingolipids --> Gangliosides, cerebrosides, and sphingomyselin

2. Mucopolysaccharides --> Heparan sulfate, dermatan sulfate, keratan sulfate, and chondroitin sulfate

3. Glycogen

- Glucocerebrosidase deficiency

- Accumulated material: Glucocerebrosides

- Tissues involved: Reticular activating system of spleen, bone, liver, and CNS

- Type I: Adult --> Spleen and skeletal involvement, reduced enzyme activity, slightly decreased longevity

- Type II: Infantile --> CNS, no enzyme activity, death at an early age

- Type III: Intermediate between Type I and Type II

- Gaucher Cells: Fibrilar deposits --> Flattened lysosomes

- 80% of Type I cases are in Ashkenazi Jews

- Hepatomegaly (2-3x)

- Splenomegaly (up to 15x)

- Thrombocytopenia --> Gaucher cells take up space in marrow

- Anemia --> Gaucher cells take up space in bone marrow

- Low WBC count

- "Bone crisis" --> Insufficient blood flow to bone

- "Erlenmeyer flask" bones --> Bone thinning

- Most common in Ashkenazi Jews

- Hexosaminidase deficiency --> Completely absent

- Accumulated material: Gangliosides

- Cytoplasmic vacuoles present and "onion-skin" filled lysosomes on EM

- Involved tissues: CNS, retina (cherry red spot), autonomic nerves, heart, spleen, liver and lymph nodes

- Infants normal at birth, then motor and mental deterioration, muscle flaccidity, blindness and obtundation after 6 months

- Life expectancy: Death in about 2-3 years

- Sphingomyelinase deficiency

- Accumulated material: Sphingomyelin

- Involved tissues: CNS and RES in spleen, liver, lymph nodes and bone marrow

- Type A: 75-80% of cases, infantile, severe CNS involvement, progressive wasting and death by age 3

- Type B: Organomegaly but no CNS involvement --> Survive to adulthood

- Zebra lines seen within cells on EM

- Multiple different enzyme deficiencies

- Nomenclature of MPS I-IV

- Hurler's syndrome is most common

- Alpha-L-iduronidase deficiency

- Accumulated material: Dermatan and heparan sulfate

- Involved tissues: Connective tissue, RES, endothelial cells, and smooth muscle cells

- Clinical Presentation: Hepatosplenomegaly, skeletal deformities, valvular lesions, and subendothelial arterial deposits (myocardial infarction)

- Facial structure: Eye widening, cataracts, short stature, etc

- Most glycogen is broken down in the cytoplasm

- Some is broken down in the lysosome by acid maltase

- Phosphorylase or Glucose-6-phosphatase deficiencies

- Hepatic type is life threatening (hypoglycemia) and the muscular type is not life threatening

- Glucose-6-phosphatase deficiency in liver

- Glycogen accumulates

- Involved tissues: Hepatocytes and renal tubular cells

- Clinical presentation: Convulsions due to hypoglycemia, hepatomegaly, growth retardation, infections, hyperlipidemia, and hyperuricemia

- Alpha-glucosidase (acid maltase) deficiency

- Glycogen accumulates in lysosomes

- Involved tissues: Generalized but heart and brain cause the most prominent symptoms

- Clinical presentation: Cardiac hypertrophy leading to heart failure, muscular weakness, and neurologic symptoms

- Death occurs in infancy

- Enzyme replacement --> Very expensive

- Organ replacement

- Bone marrow transplant

- Gene therapy/transfer

- Recurrent attacks of acute arthritis evoked by the precipitation of urate crystals into join spaces

- Crystal precipitate from supersaturated body fluids

- Leads to the chronic disabling arthritis and focal deposits of urates in other tissues

- Deposits can be found in joint capsules, perichondrial tissue, bursa, heart valves, and kidneys

- These deposits end up forming tophi --> Inflammatory foci

- 2-18% of the population has hyperuricemia

- 0.13-0.37% of the population has Gout

- 95% of gout occurs in men

- Affected women are postmenopausal

- Very rare in children

- 25% of patient's relatives have hyperuricemia --> Genetic 

- Acute arthritis

- Chronic tophaceous arthritis --> Big toe

- Tophi in soft tissue --> Big toe, helix and anti-helix of the ear, olecranon and patellar bursae, periarticular ligaments and CT

- Extremely painful due to the tremendous inflammatory response --> Release of LTB4, prostaglandins and free radicals

- Possible but rarely found in the kidney, aorta, and heart valves

- Mass of urates (crystalline or amorphous) surrounded by an intense inflammatory reaction of macrophages, lymphocytes, fibroblasts and foreign body giant cells

- Never found in CNS because urates don't cross the BBB

- New growth

- Uncoordinated cell growth exceeding normal barriers to give rise to a neoplasm (tumor/mass)

- Loss of the normal orientation of one cell to another in a particular tissue

- Pre-neoplastic

- Associated with cellular anaplasia

- Some mild forms of dysplasia can be reversible

- Lack of differentiation of cells

- Cellular and neuclear pleomophism

- Increase in N/C ration (nucleus becomes larger comparatively) 

- Prominent nucleoli

- Aneuploidy

- Hyperchromasia of nuclei

- Abnormal mitosis

- Tumor giant cells --> Multinucleated

- Extent to which neoplastic cells resemble the parent/surrounding cells

- Well, moderately or poorly differentiated

- For glandular tissues --> Ability to form glands

- For squamous tissues --> Ability to form keratin

- Cytologically cells resemble normal cells

- Well circumscribed 

- Localized --> Do not spread

- Amenable to surgical excision

- Fibroma, leiomyoma, lipoma, chondroma, endothelioma

- Adenoma and papilloma/epithelioma

- Polyp: Growth that projects above the surface of the epithelium --> Glandular or squamous and benign or malignant

- Lymphoma

- Melanoma

- Seminoma

- Mesothelioma

- Hepatoma

- Hamartoma: Not strictly a neoplasm but results from disorganized collection of tissue

- Teratoma: From germ cells --> Can be benign, immature or malignant

- Actually malignant

- Invasion and destruction of adjacent tissues

- Spread to distant sites via lymphatics or blood vessels (metastasis)

- Not well circumscribed

- Varying degrees of anaplasia

- Grading: Well, moderately or poorly differentiated

- Sarcoma: Mesenchymal derived

- Carcinoma: Epithelial derived --> Adenocarcinoma, squamous cell carcinoma, and transitional cell carcinoma

- T: Size of primary tumor

- N: Number of nodes involved

- M: Presence of metastasis

- Staged I-IV

- Present at birth

- Most common cause of mortality in the first year of life

- Includes malformations, disruptions, deformations, sequence and syndromes

- Primary errors of morphogenesis in which there is an intrinsically abnormal embryonic or fetal developmental process

- Usually multifactorial (multiple genetic loci)

- Single body systems --> Congenital heart defects and anencephaly

- Multiple system malformations

- Causes: Genetic, environmental and multifactorial

- Environmental malformation

- Facial features: Short palpebral fissures, flat midface, short nose, indistinct philtrum, thin upper lip, epicanthal folds, low nasal bridge, minor ear anomalies, and micrognathia

- Congenital Rubella Syndrome --> Tetrad

- Characterized by cataracts, heart defects, deafness, and mental retardation

- Heart defects include persistent ductus arteriosus, pulmonary artery hypoplasia or stenosis, ventricular septal defect, and tetralogy of Fallot

- Most common fetal viral infection

- Presentation: Mental retardation, microencephaly, deafness, and hepatosplenomegaly

- Gestational age of less than 37 weeks and weight less than 2500 grams

- Second most common cause of neonatal mortality

- Risk factors for premature birth: Preterm premature rupture of placental membranes (PPROM), intrauterine infection, uterine, cervical, and placental abnormalities, and multiple pregnancies

- Possibly due to infections of chlamydia and gonorrhea

- Common in preterm infants and infants delivered by cesarean section --> Vaginal delivery compresses lungs to stimulate them

- Lungs of normal size, solid, airless, and reddish purple but alveoli are poorly developed and necrotic cellular debris in terminal bronchioles

- Dyspnea and fine rales heard on physical exam

- Also common with maternal history of diabetes --> Increased insulin --> Insulin inhibits surfactant production

- Caused by immaturity of the lungs and a deficiency in surfactant

- Leads to collapsed lungs, atelectasis and reduced lung compliance

- Results of deposition of protein/fibrin-rich exudate in the alveolar space --> Hyaline membranes

- Positive pressure ventilation

- Consequence: Retinopathy of prematurity or bronchopulmonary dysplasia

- Bronchopulmonary dysplasia: Dilated airspaces, bronchial hyperplasia, squamous metaplasia, alveolar wall thickening and fibrosis

- Incidence of disease is inversely proportion to gestation age

- Presentation: Abdominal distention, absent bowel sounds, and bloody stools

- Pneumotosis intestinalis (air filled sacs below mucosa) and ischemic bowel possible

- Intraventricular and subependymal hemorrhage

- Liquefactive necrosis

- Hemorrhage increases intracranial pressure, damage to the brain substance, hernational of medulla or brain stem and fatal depression of brain stem function

- Disease of unknown cause

- Sudden death of an infant under 1 year of age which remains unexplained after a thorough case of investigation, including performance of a complete autopsy, examination of the death scene, and review of the clinical history

- Most commonly caused infections such as viral myocarditis or bronchopneumonia or an unexpected congenital anomaly

- Multifactorial condition --> Delayed development of arousal and cardiorespiratory control

- Autosomal recessive disease --> Most common in Caucasian populations

- CFTR gene (chromosome 7q31.2) defect

- Affects fluid secretion by exocrine glands (pancreas, salivary glands, GI and respiratory tracts, and liver)

- Meconium ileus --> Meconium cannot pass due to lack of secretion --> Can cause perforation and peritonitis

- May also result in azoospermia, infertility, and congenital absence of bilateral vas deferens 

- Ozone: Present in smog --> Respiratory irritant (cough, chest discomfort and inflammation)

- Carbon Monoxide: Produced by fossil fuel burning --> Insidious CNS depression (Headaches, dizziness, loss of motor control, and coma)

- Particulates: Produced by combustion products and mineral dusts --> Pulmonary inflammation and fibrosis and heart abnormalities

- Activate inflammation through the release of cytokines

- Most dangerous

- Can reach the terminal respiratory units

- Can cross the epithelial lining

- Can trigger inflammation and arrhythmias

- Coal mining --> Black lung

- Formaldehyde: Found in foam insulation, glues and wood products --> Cause asthma and contact dermatitis

- Asbestos fibers: Found in insulation, floor and ceiling tiles <1970s --> Can cause mesothelioma, lung fibrosis & cancer

- Radon: Found in the soil --> Can cause lung cancer due to inhalation of radon

- Carbon tetrachloride, chloroform, methylene chloride, benzene and gasoline

- Methylene chloride --> Found in paint removers

- Are occupational and consumer hazard

- Easily absorbed by the lungs and GI tract and less easily absorbed by skin

- Symptoms: Headache, dizziness, liver and kidney toxicity

- Vinyl chloride, phthalate esters, bisphenol-A, and polychlorinated biphenyls (PCBs)

- Both occupational and consumer hazards

- Route of exposure: GI, lung, and skin absorption

- Symptoms: Numerous toxic effects

- Found in PVC/plastic products

- Can be absorbed through skin and lungs

- Effects: Can cause liver angiosarcoma

- Found in flexible plastics such a shower curtains, toys, adhesives, and catheters

- Effects: Reproductive toxin in animals and unknown effect in humans

- Found in polycarbonate bottles and the coating of food cans

- Effect: Estrogen mimic --> Proliferative --> Reproductive cancers, etc

- Found and persist in capacitors, transformers, vacuum pump oils, and hydraulic fluids --> Banned in 1977

- Effect: Chloracne, rashes, liver damage, endocrine disorders, and probably a carcinogen

- Acne-like eruption from exposure to chlorinated organic compounds

- Causes squamous metaplasia of the sebaceous glands

- Also called Yusho disease

- Effects depend on the type of metal and the level of exposure

- Heavy metals --> Mercury, lead, cadmium, chromium, and nickel

- Produced from coal burning, thermometers, electical switches, fungicides, disinfectants, fluorescent lamps, fish and shellfish and dental amalgam

- Mechanism of action: Causes cell membrane damage by binding of mercury to sulfhydryl groups in proteins

- Effects: Kidney dysfunction, cognitive imairment, mental retardation and death

- Exposure sources: Lead mining, spray painting of bridges and boats, drinking water, old painted surfaces, and contaminated soil

- Absorption: Lung inhalation or oral ingestion

- Much more readily absorbed by children

- Effects in adults: Abdominal pain, headache and memory loss

- Effects in children: Fatigue and mental deterioration

- Mechanism of Action: Binds to sulfhydryl groups, interferes with ferrochelatase, and competes with calcium

- "Erlenmeyer flask" bones and basophilic stippling of RBCs commonly seen causing anemia

- Major concern because of the widespread and heavy use

- 1 billion pounds/year applied in the US for agriculture, homes and institutions

- Dermal, ingestion and inhalation possible

- Effects: Acute vs. delayed

- Insectiides, Herbicides, Fungicides, Rodenticides, and Fumigants

- Chlordane, lindane, and DDT

- Effects: Cancer, neurotoxicity, hepatotoxicity, possible endocrine disruption, excitability, dizziness, weakness, tremor and convulsions

- Lab test: Presence of pesticide metabolites in blood

- Banned in the US

- Parathion, Diazinon, Dursban, and Melathion

- Mechanism of Action: Irreversibly inhibits cholinesterase

- Effect: Blurred vision, nausea, muscle spasms, paralysis, and unconsciousness

- Lab test: Cholinesterase activity in blood

- Carbaryl and Baygon

- Mechanism of Action: Reversibly inhibits cholinesterase

- Effect: Diarrhea, abdonimal pain and respiratory difficulty

- Lab test: Carbamate metabolites in the urine

- > 4,000 chemicals

- > 100 carcinogens --> Polycyclic aromatic hydrocarbons, benzanthracene, N-nitroso diethylamine, and heavy metals (arsenic, nickel, cadmium, and chromium)

- Contains irritants such as NO and formaldehyde

- Cilia toxins --> Hydrogen cyanide and ammonia

- Also contains nicotine and carbon monoxide

- Effects: Emphysema, lung cancer (Bronchogenic carcinoma), and ischemic heart disease (atherosclerosis)

- Named after the tobacco plant

- Readily crosses the blood-brain barrier

- Mechanism of action: Nicotinic acetylcholine receptor agonist

- Elicits feelings of euphoria and satisfaction --> Addictive

- Also is a chemoattractant for neutrophils --> Inflammation

1. Protease-antiprotease imbalance: Genetic deficiency in alpha-1-antitrypsin (AAT)

- Neutrophils normally release elastase to break down elastin in tissues

- Neutrophils are greatly recruited to lungs in smokers by nicotine and the reactive oxygen species in smoke

- Leads to an overall breakdown of elastin --> Loss of lung compliance, etc

2. Oxidant-Antioxidant Imbalance

- Lung normally has an abundance of antioxidants

- Cigarette smoke contains lots of free radicals --> Deplete the antioxidants

- Reactive oxygen species also inactivate AAT

- 15 million alcoholics in the US --> Alcohol dependence

- Acute effects: CNS depressant

- Chronic effects: Toxicity to liver, pancreas, heart, GI tract, and fetus

- Mechanism of Action: Ethanol depletes NAD in the body, generates toxic acetaldehyde and destabilizes cell membranes

- Also leads to fatty acid deposition in the liver due to fatty acid oxidation decrease due to depleted NAD and increased fatty acid production due to increased levels of NADH

- Alcoholic hepatitis: Fever, malaise, due to lytic necrosis and inflammation --> Reversible reaction

- Alcoholic cirrhosis: Jaundice and weakness due to extensive fibrosis and loss of hepatocytes

- Cirrhosis will lead to organ failure

- 10x greater than the general population

- Linked the cancers of the oral cavity, pharynx, esophagus, liver, prostate and breast

- Suspected mechanism: Acetaldehyde --> Known toxin, mutagen, and carcinogen

- Moderate alcohol intake (1 drink for women and 2 for men) --> Decreased risk of CAD, ischemic stroke, gallstones and type 2 diabetes

- 165,000 deaths/year in the US --> Leading cause of death in 1-44 yr age group

- Trauma --> Caused by a force of sufficient magnitude is applied to the body --> Can be accelerating/decelerating, blunt/sharp, or accidental/deliberate

- Factors affecting severity: Mass, velocity, surface area, type of tissue, and presence of disease --> Velocity means more than mass

- Laceration: Splitting due to excessive stretching of an organ

- Unintentional decline in core temp <35 C

- Mild --> 32-35 C --> Stable hemodynamically with vigorous shivering

- Moderate --> 28-32 C --> Decreased oxygen consumption, CNS depression, and no shivering/paradoxical disrobing

- Severe --> <28 C --> Ventricular fibrillation, pulmonary edema and coma/death

1. Suppression of vital metabolism

2. Crystallization of cell water

3. Increased permeability of vessels

4. Ischemia, anoxia, and infarction

- Trench foot: Can be caused by 12 hour submersion in 50 F water

- Local hyperthermia

- Severity depends on percent of body surface, intensity of the heat, and the duration

- Superficial, partial thickness, and full thickness burns

- Superficial and partial thickness are very painful due to presence of nerve endings

- Full thickness burns don't hurt --> Nerves have died

- Due to high ambient temperature and humidity

- Risk factors: Advanced age and physical stress

- Prolonged core temp >40 C --> Peripheral vasodilation --> Reduced blood flow to brain/heart leading to confusion, coma, and death

- Severity due to:

1. Type and intensity of current --> AC current worse

2. Path of current

3. Resistance of tissues --> Skin very resistant so burns can occur but visceral organs good conductors

4. Duration of exposure

- Lightning print --> Common in lightning strikes

- Emission, transmission and absorption of energy

- Distributed across the electromagnetic spectrum

- Ionization: Transfer of the radiation's energy to target molecules --> Causes ejection from their orbits

- Non-ionizing radiation: Radio waves, microwaves, infrared, visible light, and ultraviolet

- Ionizing radiation: X-rays, gamma rays, alpha particles, beta particles, and neutrons

- Direct: Direct mutation of DNA or mitotic failure

- Indirect: Production of free radicals due to radiation --> Interaction with cytoplasmic components --> Biochemical change --> Cell damage/death

- Kill cells, prevent mitosis, alter enzymes, and causes mutation in DNA

- Effects depend on the total absorbed dose and the rate of delivery

- Genetic effects: Point mutation, deletion, inversion, translocation, and nondisjunction

- Increased risk for cancers --> Skin cancer, leukemia and thyroid cancer have been associated

- High Sensitivity: <25 Grays needed for damage --> Lymphoid, hematopoietic tissues, germ cells and GI epithelium

- Moderate Sensitivity: Skin, blood vessels, squamous epithelium, and growing bone and cartilage

- Low Sensitivity: >50 Grays needed for damage --> Kidney, muscle, brian, endocrine organs, and adult bone and cartilage

- Depends on the mitotic and proliferative activity of the organ

- Radiodermatitis --> Thinning of skin --> Loss of hair follicles and glands

- Whole body radiation and aplastic anemia --> Seen in the bone marrow --> Very susceptible to infection

- Radiopneumonitis --> Severe fibrosis due to radiation exposure --> Severe pulmonary distress

- 2-10 Sievert exposure --> Bone marrow effect --> Anemia, hemorrhage, and infection --> Death within 2-6 weeks without marrow transplant

- 10-20 Sievert exposure --> GI tract effect --> Sloughing of epithelium and infection --> Death in 5-14 days

- >50 Sieverts --> Edema and necrosis of the CNS --> Death in 1-4 hours

- Cataract formation

- Mental defects in developing children

- Cancer

- Mutations in germ cells which will manifest in future generations

- UVA, UVB, and UVC rays

- UVC and part of the UVB rays stopped by ozone in atmosphere

- Some UVB and UVA reach earth surface

- Sunscreen stops UVB rays

- Sunburn caused by UVB rays

- Acute effects: Erythema, pigmentation and depletion of Langerhans cells (infection risk)

- Chronic effects: Degeneration of elastin and collagen and cataracts

- Increased incidence of squamous cell carcinoma, basal cell carcinoma, and malignant melanoma

- UVB rays cause pyrimidine dimers --> Transcriptional errors and can eventually lead to cancer

- From cell phone towers, microwaves, and cell phones

- High levels can cause burns and possibly cancer

- Unknown effect of long term low level exposure

- Little or no risk except for "prolonged and heavy" mobile phone use

- WHO classified cell phones as "possibly carcinogenic to humans" --> Long term studies needed

- Chemistry & immunology

- Hematology

- Microbiology

- Blood bank

- Laboratory Information Services (LIS)

- Point-of-care (POC) testing

- Electrolytes

- LFTs

- Blood gases

- Cardiac markers

- Endocrine assays

- Therapeutic drug monitoring

- Tumor markers

- Toxicology (tox screen)

- Immunology assays

- CBC

- Body fluid analysis

- Coagulation testing

- Bacteriology --> Culturing and antibiotic sensitivities

- Mycology

- Virology

- Parasitology

- Molecular diagnosis --> Viral load, genotyping and chlamydia/GC

- Transfusion service

- Type/screen or cross-matches for patients

- Some blood banks also collect blood from autologous or volunteer blood donors

- Testing performed at the bedside

- Usually performed by nurses/nurses aids

- Most common --> Fingerstick

- Computer system that is critical to correct ordering, resulting and reporting of lab tests

- Needs to be able to interface with the hospital information system --> Receive orders and report results

- Also needs to interface with lab instruments

- Whether patient actually fasted for fasting test

- Correct label --> Correct patient --> Correct tube

- Correct order of tubes: blood culture, red, blue, gold, light green, and lavender

- Evaluate if blood sample was collected downstream of the infusion site --> Erroneous results

- Accuracy: Getting the correct result

- Precision: Reproducibility of assay

- Maintained through quality control protocols for each assay --> Run at least daily, usually once a shift

- Presence of substance in the blood that interferes with measurement

- Icterus: Dark yellow colored plasma --> Bilirubin

- Lipemia: Turbidity in sample (cloudy) --> Lipid in plasma, possibly due to eating a fatty meal just previously

- Hemolysis --> Red color to plasma --> RBCs damaged

- Some analyte measurements are more or less susceptible to alteration due to hemolysis

- Falsely elevated PSA value

- Due to anti-mouse IgG antibodies --> Present in a small population of normal individuals

- Always use the correct reference ranges --> Not that different tests/protocols use different ranges

- Positive Predictive Value: How likely is it that someone who has disease tests positive

- Negative Predictive Value: How likely is it that someone without disease tests negative

- Sensitivity: Ratio of people who tested positive who actually have disease

- Specificity: Ratio of people who tested negative who actually don't have disease

- Causes valvular regurgitation between the LA and LV

- Coagulative necrosis results due to ischemia

- Severe regurgitation --> Decreased cardiac output, increased pulmonary BP, pulmonary edema, left atrial dilation, and right ventricular hypertrophy and failure

- Hypereosinophilia seen on section --> Cellular shrinkage, loss of basophilicity due to loss of ribosomes, and denaturation of proteins

- Endocardial myocytes --> Spared from necrosis due to oxygenation from blood in LV

- Ballooning/Hydropic degeneration occurs --> Sub-lethal cell injury

- Leads to apoptosis induction --> Acidophil bodies

- Fatty change --> occurs with Hep C infection

- Infiltration of macrophages to clean up the apoptotic cells

- Hepatocytes begin to fail --> Build up in bilirubin within cells --> Brown staining

- Lytic necrosis occurs around central vein --> Surrounded by activated T-cells --> Hepatocytes disappear

- CD8 T-cells bind FAS ligand to activate apoptosis in hepatocytes infected with Hep virus (extrinsic pathway)

- Presents with fever and lower right quadrant pain

- Acute inflammation with fibrin

- On cross section --> Neutrophil infiltration with coagulative necrosis (acute inflammation)

- Fibrinous exudate seen on the external surface of the appendix

- Infection can eat through the entire wall --> Ruptured appendix --> Can lead to peritonitis

- Treatment: Appendectomy and antibiotics

- Due to a minor metabolite of acetaminophen

- Metabolite --> Leads to coagulative necrosis around the central veins

- Use ALT/AST, alkaline phosphate, bilirubin, and a prothrombin time to determine liver functioning

- Acetaminophen levels measured and tox screen performed

- Treat with IV acetylcysteine

- Acetaminophen levels too high --> Lead to liver failure and death

- On autopsy --> Coagulative necrosis seen around central veins and fat deposition (steatosis) within cells around the portal triad

- This pattern of damage reiterates the thought that a metabolite is the source of the damage --> Hepatic acinus flow (zones 1-3) --> Zone 3 damage

- Myopathic glycogenoses disease

- Deficient Enzyme: Phosphorylase

- Symptoms: Painful cramps with exercise and failure to induce elevated lactate levels in blood