Pathology Principles Flashcards
1
Q
What to look for in Gross Examination
A
- The organ
- Size
- Shape
- Consistency
- Color
2
Q
What to look for in light Microscopic Examination (H and E)
A
- Hematoxylin: blue or purple (Nuclei, Bacteria and Calcium) [NBC]
- Eosin: pink or red (Proteins)
3
Q
What to look for in light Microscopic Examination (Periodic Acid-Schiff [PAS])
A
Carbohydrates in the following conditions:
- DM
- Glycogen storage diseases
- Alpha-1 antitrypsin deficiency
- Fungi
- Whipple disease
- AML-M6
- Paget’s disease
4
Q
Causes of Cellular Injury
A
- Hypoxia
- Infection
- Immunologic reactions
- Congenital disorders
- Chemical injury
- Physical injury
- Nutritional or vitamin imbalance
5
Q
What are the critical intracellular systems that are susceptible to injury
A
- DNA
- ATP production (mitochondria)
- Cell membranes
- Protein synthesis
6
Q
Important mechanisms of cell injury
A
- Oxygen free radicals (superoxide anion [O2’-], hydroxyl radical [OH’], and hydrogen peroxide [H2O2])
- ATP depletion
- Increased cell membrane permeability
- Influx of Calcium (uncontrolled)
- Release of cytochrome c from mitochondria which triggers apoptosis
7
Q
Protective Factors against free radicals
A
- Anti-oxidants (vitamins A, C, E and Selenium)
- Certain metal carrier proteins like transferrin and ceruloplasmin
- Superoxide dismutase (superoxide —> hydrogen peroxide)
- Glutathione peroxidase (hydroxyl ions or hydrogen peroxide —-> water)
- Catalase (hydrogen peroxide —-> oxygen and water)
8
Q
Reversible changes in cellular injury due to decreased oxidative phosphorylation
A
- Cell swelling due to decreased Na+/K+ ATPase pump which results in influx of Na+ and efflux of K+
- Decreased pH due to increased glycolysis and increased lactic acid
- Decreased protein synthesis due to ribosomal detachment
9
Q
Irreversible changes in cellular injury due to decreased oxidative phosphorylation
A
Severe membrane damage which results in influx of Ca++ and leak of cytoplasmic enzymes out of the cell
10
Q
Cardiac Markers
A
- Troponin I
- CK-MB
- LDH (means there something died)
- Myoglobin
- AST
11
Q
Liver Markers
A
ALT > AST (except in alcoholic hepatitis in which AST > ALT)
12
Q
Pancreas Markers
A
- Amylase (sensitive)
- Lipase (specific)
13
Q
Biliary tract obstruction markers
A
First do Alkaline Phosphatase if +ve (which is +ve in bone disease too) then do GGT
14
Q
Coagulative Necrosis
A
- Due to ischemia
- Dry gangrene
- Micros. loss of nucleus but preservation of cellular shape
- Proteins denature then enzymatic degradation
- Most organs including heart, liver and kidney
15
Q
Liquefaction Necrosis
A
- Cellular destruction by hydrolytic enzymes
- Wet gangrene
- Enzymatic degradation then proteins denature
- Abscess, brain infarcts and pancreatic necrosis
16
Q
Caseous Necrosis
A
- Combination of coagulation and liquefaction
- Gross. soft, friable, cottage-cheese like
- Micros. granuloma with peripheral giant cells
- TB and Fungi
17
Q
Fibrinoid Necrosis
A
- Due to acute immunologic injury (hypersensitivity reaction type II and III) and malignant hypertension
- Micros. eosinophilic (pink) homogeneous appearance
18
Q
Fat Necrosis
A
- Gross. chalky white appearance
- Micros. fat cells without peripheral nuclei. saponification of fat (combined with calcium) appears dark blue on H and E stain
- Damaged cells release lipase which breaks down triglycerides in fat cells
- Either enzymatic like acute pancreatitis or non-enzymatic like trauma to the breast
19
Q
Apoptosis (Definition and morphologic appearance )
A
- Programmed cell death without inflammatory response
- It involves a single cell or a small groups of cells
- Cells shrink and has dense eosinophilic cytoplasm then fragmentation of the nucleus
- DNA laddering (fragments in multiples of 180 bp) is a sensitive indicator of apoptosis
20
Q
Cellular Adaptive Responses to Injury
A
- Atrophy
- Hypertrophy
- Hyperplasia
- Metaplasia
- Dysplasia
21
Q
Inflammation Hemodynamic Changes
A
- Initial transient vasoconstriction
- Massive vasodilatation mediated by Histamine, bradykinin, and prostaglandins
- Increased vascular permeability by Histamine and Serotonin (platelets), bradykinin, and leukotrienes (LTC4, LTD4, LTE4)
- Blood stasis due to increased viscosity, allows neutrophils to marginate
22
Q
Neutrophils Primary (azurophilic) granules content
A
- Myeloperoxidase
- Phospholipase A2
- Lysozyme (hydrolysis of 1,4-beta-linkages in bacterial walls)
- Elastase
- Defensins (microbicidal peptides)
- Bacterial permeability increasing protein (BPI)
23
Q
Neutrophils Secondary (specific) granules content
A
- Phospholipase A2
- Lysozyme
- Leukocyte alkaline phosphatase (LAP)
- Collagenase
- Lactoferrin (chelates iron)
- Vitamin B12 binding proteins
24
Q
Macrophages enzyme content
A
- Acid hydrolases
- Elastase
- Collagenase
25
Q
Selectins in Neutrophil migration and adhesion
A
- Weak binding
- Initiate rolling
- P-selectins and E-selectins on endothelial cells bind Sialyl-Lewis X and PSGL-1 on leukocytes
- GlyCam-1/CD34 on endothelial cells bind L-selectins on leukocytes
26
Q
Integrins in Neutrophil migration and adhesion
A
- Stable binding with adhesion
- ICAM-1 (CD54) on endothelial cells binds LFA-1 and MAC-1 (CD11/18) on leukocytes
- VCAM-1 (CD106) on endothelial cells binds VLA-4 on leukocytes
27
Q
Defects in neutrophil adhesion (Conditions)
A
- DM
- Corticosteroid use
- Acute alcohol intoxication
- Leukocyte adhesion deficiency (AR disease)
28
Q
Leukocytes Emigration (diapedesis)
A
- Post-capillary venule
- Dissolve the basement membrane via collagenase (type 4 metaloprotease [zinc dependent])
- PECAM-1 (CD31) on endothelial cells and leukocytes
29
Q
Neutrophils Chemotactic factors
A
- N-formyl-methionine
- Leukotriene B4 (LTB4)
- Complement system product C5a
- IL-8
30
Q
Factors that modulate the expression of adhesion molecules in inflammation
A
- Histamine
- Thrombin
- TNF-alpha
- IL-1
31
Q
Important Opsonins
A
- Fc portion of IgG
- Complement system product C3b
- Plasma protein such as collectins (which bind to bacterial cell walls)
32
Q
Defects in Phagocytosis
A
Chediak-Higashi syndrome (AR, neutrophils have giant granules, albinism, LYST gene)
33
Q
Deficiency of Oxygen-dependent killing
A
- Chronic granulomatous disease (X-linked or AR) with NADPH oxidase deficiency
- Myeloperoxidase deficiency (AR) a condition characterized by infections with candida
- Nitroblue Tetrazolium Reduction test (+ve is purple-blue and means there is enzyme so normal [no disease])
34
Q
Histamine (Production, Function, and Triggers)
A
- Produced by basophils, platelets, and mast cells
- Vasodilation and increased vascular permeability.
- Triggers are IgE-mediated mast cell reactions, physical injury, anaphylotoxins (C3a and C5a), and cytokines (IL-1)
35
Q
Serotonin (Production and Function)
A
- Produced by platelets
- Vasodilation and increased vascular permeability.
36
Q
Kinin system (First and end products, and Function)
A
- Activated Hageman factor (factor XII) and Bradykinin
- Vasodilation, increased vascular permeability, bronchoconstriction and pain
37
Q
Arachidonic acid products (Cyclooxygenase pathway)
A
- Thromboxane A2 produced by platelets and causes vasoconstriction and platelet aggregation
- Prostacyclin (PGI2) produced by vascular endothelial cells and cause vasodilation and inhibition of platelet aggregation
- Prostaglandin E2 causes pain
- Prostaglandins PGE2, PGD2, and PGF2 cause vasodilation
38
Q
Arachidonic acid products (Lipoxygenase pathway)
A
- Leukotriene B4 (LTB4) causes neutrophil chemotaxis
- Leukotrienes C4, D4, E4 cause vasoconstriction
39
Q
Mediators of Pain
A
- Bradykinin
- Prostaglandin E2
40
Q
Mediators of Fever
A
- Cytokines IL-1, IL-6 and TNF-alpha
- Prostaglandins
41
Q
Outcomes of Acute Inflammation
A
- Complete resolution with regeneration
- Complete resolution with scarring
- Abscess formation
- Transition to chronic inflammation
42
Q
Pathologic forms of Calcification
A
- Dystrophic calcification
- Metastatic calcification
43
Q
Dystrophic Calcification (Definition and Examples)
A
- Precipitation of calcium phosphate in dying or necrotic tissues
- Fat necrosis (saponification), psammoma bodies (laminated calcifications in meningiomas and papillary carcinomas of the thyroid and ovary), Monckeberg medial calcific sclerosis in arterial walls, atherosclerotic plaques, TB (lungs and pericardium), liquefactive necrosis of chronic abscesses, infarcts, thrombi, schistosomiasis, and congenital CMV + toxoplasmosis
44
Q
Metastatic Calcification (Definition and Examples)
A
- Precipitation of calcium phosphate in normal tissues due to hypercalcemia (supersaturated solution)
- Hyperparathyroidism, parathyroid adenomas, paraneoplastic syndrome, vitamin D intoxication, Milk-alkali syndrome, sarcoidosis, Paget’s disease, multiple myeloma, metastatic cancer to bone, long-term dialysis, calciphylaxis, and warfarin
note: it is usually located in interstitial tissues of stomach, kidneys, lungs and blood vessels (these tissues lose acid quickly, increased pH favor deposition)
45
Q
Causes of Chronic Inflammation
A
- Following a bout of acute inflammation
- Persistent infections
- Infection with certain organisms including viral infections, mycobacteria, parasitic and fungal infections
- Autoimmune diseases
- Response to foreign material
- Response to malignant tumors
46
Q
Macrophages names in different tissues
A
- Monocytes (blood stream)
- Histiocytes (connective tissues)
- Pulmonary alveolar macrophages (lungs)
- Kupffer cells (liver)
- Osteoclasts (bone)
- Microglia (brain)
Note: macrophages secrete a wide variety of active products called monokines and may be modified into epithelioid cells by INF-gamma in granulomatous processes
47
Q
Granulomatous diseases (Examples)
A
- Bacterial:
- Mycobacteria (TB [caseating granuloma], leprosy)
- Bartonella henselae (Cat-scratch fever)
- Listeria monocytogenes (granulomatosis infantiseptica)
- Treponema pallidum (tertiary syphilis)
- Fungal infections like coccidioidomycosis
- Parasitic infections like schistosomiasis
- Chronic granulomatous disease
- Foreign material like Beryllium, talcosis, hypersensitivity pneumonitis
- Auto-inflammatory like sarcoidosis, Crohn disease, Primary biliary cirrhosis, Subacute (de Quervain/granulomatous) thyroiditis, granulomatosis with polyangiitis (Wegener), Eosinophilic granulomatosis with polyangiitis (Churg-Strauss), Giant cell (temporal arteritis, and Takayasu arteritis
48
Q
Tissues classification according to their regenerative capacities
A
- Labile cells which regenerate throughout life like surface epithelial cells, hematopoietic cells and stem cells
- Stable cells which replicate at low level throughout life and have the capacity to divide if stimulated by some initiating event like hepatocytes, renal proximal tubule cells and endothelium
- Permanent cells which have very low level of replicative capacity like neurons and cardiac muscle
49
Q
Tissue Repair growth factors
A
- Transforming growth factor-beta (TGF-beta)
- Platelet derived growth factor (PDGF)
- TNF-alpha and IL-1
- Fibroblast growth factor (FGF)
- Vascular endothelial growth factor (VEGF)
- Epidermal growth factor (EGF)
50
Q
Granulation tissue contents
A
- Active fibroblasts
- Capillary proliferation
51
Q
TGF-beta and EGF functions
A
- Both are involved in wound healing and regeneration
- Both bind to EGF receptor
- EGF stimulates cell growth via tyrosine kinases (e.g., EGFR/ErbB1)
- TGF-beta stimulates angiogenesis, fibrosis and cell cycle arrest
52
Q
VEGF function
A
Induces new vessel growth during growth, repair and regeneration
53
Q
Factors inhibiting tissue repair
A
- Diabetes
- Diseases affecting collagen and elastic fibers (scurvy, Ehlers-Danlos syndrome, osteogenesis imperfecta and Marfan syndrome)
- Foreign bodies
- Inadequate blood supply
- Infection
- Large size or extent of damage
- Mechanical disruption of wound healing
- Malnutrition or specific nutrient deficiency
- Malignancy
- Medications including glucocorticoids
- Obesity
- Old age
54
Q
Collagen types (Location)
A
- Type I: skin, bone, tendons and most organs
- Type II: cartilage and vitreous humor
- Type III (reticulin): granulation tissue, embryonic tissue, uterus, aorta and keloids
- Type IV: basement membrane (alpha-3 subunit is the the target of Goodpasture syndrome which is abundant in kidneys and lungs)
- Type V: hair and placenta
55
Q
Collagen (Important enzymes)
A
- Hydroxylation by prolyl-4-hydroxylase and lysyl-hydroxyalse both are vitamin C dependent
- Cross-linking by lysyl oxidase which is copper dependent (Menke’s syndrome [Cu deficiency])
56
Q
Collagen and diseases
A
- Type I: Osteogenesis imperfecta, Ehler-Danlos syndrome and Caffey’s disease (infantile cortical hyperostosis)
- Type II: Collagenopathy
- Type III: Ehler-Danlos syndrome and Dupuytren’s contracture
- Type IV: Alport’s syndrome and Goodpasture’s syndrome
- Type V: Ehler-Danlos syndrome (classical)
- Type VII: forming anchoring fibrils in dermoepidermal junctions. Epidermolysis bullosa dystrophica
- Type XVII: Bullous pemphigoid and certain forms of junctional epidermolysis bullosa
- Excessive deposition of collagen occurs in scleroderma
57
Q
Basement Membrane composition
A
- Collagen type IV
- Proteoglycnas (heparan sulfate) which is responsible for the -ve charge. It is lost in Kimmelstiel-Wilson syndrome (diabetic nephropathy)
- Laminin
- Fibronectin
- Entactin
58
Q
Apoptosis (Intrinsic or Mitochondrial pathway)
Mechanism(s)
A
- Increase the permeability of mitochondrial membranes will release second mitochondrial-derived activator of caspases (SMACs) into cytosol; which then bind to Inhibitors of Apoptosis proteins (IAPs) and deactivate them; then caspases will do the apoptosis
- Formation of a channel in the outer membrane of mitochondria called mitochondrial-apoptosis induced channel (MAC) will release cytochrome c to cytosol which binds Apoptotic-protease activating factor-1 (Apaf-1) which binds to pro-caspase 9 and form a protein complex known as apoptosome which cleaves pro-caspase 9 to form the active caspase 9 which in turn activates the effector caspase 3
- Caspase-independent apoptosis: release of apoptosis inducing factor (AIF) from mitochondrial membranes which then diffuse to the nucleus and causes chromatin condensation and DNA fragmentation
59
Q
Apoptosis (Intrinsic or Mitochondrial pathway)
Regulators
A
- Inhibitors of apoptosis proteins (IAPs): all of them inhibit apoptosis usually by binding directly to caspases like X-linked inhibitor of apoptosis (XIAP), cellular inhibitor of apoptosis proteins (cIAP-1 and cIAP-2), NAIP, Livin and Survivin
- Bcl-2 family of proteins which either
- Induce apoptosis (pro-apoptotic) like Bax, Bak, Bok, Bim and BAD
- Inhibit apoptosis (anti-apoptotic) like Bcl-2, Bcl-xL and Bcl-w
- p53 which stimulates apoptosis when DNA repair is impossible
60
Q
Apoptosis (Extrinsic or Death receptor pathway)
Mechanism(s)
A
- TNF path: TNF-alpha binds to TNF receptor 1 (TNFR1) which activates TNF-receptor-associated death domain (TRADD) which activates Fas-associated death domain (FADD) which in turn activates caspase 8 which initiates apoptosis
- Fas path: first apoptosis signal ligand (FasL) binds to Fas receptor (CD95) which activates FADD which in turn activates caspase 8 which initiates apoptosis
- Cytotoxic T-cell release of perforin and granzyme B
- Caspase-independent apoptosis: increased calcium influx into cells will activate a calcium-binding protease called calpain
61
Q
Apoptosis (Extrinsic or Death receptor pathway)
Regulators
A
- FLIP protein which blocks the activation of caspase 8
- Bcl-2 family of proteins
- p53 which stimulates apoptosis when DNA repair is impossible
62
Q
Caspases
A
- Highly conserved, cysteine-dependent aspartate specific proteases
- Initiator caspases are caspase 2,8,9,10,11 and 12
- Effector caspases are caspase 3,6 and 7
- Digest nuclear and cytoskeletal proteins and also activate endonucleases
63
Q
Apoptosis (Intrinsic or Mitochondrial pathway)
Examples
A
- Involved in tissue remodeling in embryogenesis
- After cellular exposure to injurious stimuli like radiation, toxins and hypoxia
- If Bcl-2 is over-expressed like in follicular lymphoma t[14;18] then Apaf-1 is overly inhibited which lead to decrease caspase activation and tumorigenesis
64
Q
Apoptosis (Extrinsic or Death receptor pathway)
Examples
A
- Fas-FasL interaction is necessary in thymic medullary negative selection
- Mutations in Fas will increase the # of circulation self-reacting lymphocytes due to failure of clonal deletion
- Defective Fas-FasL interaction will cause autoimmune lymphoproliferative syndrome
65
Q
Outcomes of Chronic Inflammation
A
- Scarring
- Amyloidosis
66
Q
Chromatolysis
A
- Reaction of neuronal cell body to axonal injury
- Changes reflect increase protein synthesis in effort to repair the damaged axon. Characterized by:
- Round cellular swelling
- Displacement of the nucleus to the periphery
- Dispersion of Nissl substance throughout cytoplasm
- Concurrent with Wallerian degeneration of axon distal to site of injury
- Macrophages remove debris and myelin
67
Q
Hypertrophic scar vs Keloid
Collagen synthesis, Collagen organization, extent of scar, scar evolution, recurrence and predisposition
A
- H: increased / K: too much increased
- H: parallel / K: disorganized
- H: Confined to borders of original wound / K: extends beyond borders of original wound with “claw-like” projections
- H: possible spontaneous regression / K: possible progressive growth
- H: Infrequent / K: Frequent
- H: None / K: increased incidence in ethnic groups with dark skin
68
Q
Fibroblast Growth factor (FGF)
Function
A
stimulates angiogenesis
69
Q
Metalloproteinases
Function
A
Tissue remodeling
70
Q
Platelet derived growth factor (PDGF)
Source and Function
A
- Secreted by activated platelets and macrophages
- Induces vascular remodeling, smooth muscle cell migration and stimulates fibroblasts growth for collagen synthesis
71
Q
Wound Healing Inflammatory phase
Time, Effector cells and Characteristics
A
- Up to 3 days after wound
- Platelets, neutrophils and macrophages
- Clot formation, increase vessel permeability and neutrophil migration into tissue, macrophages clear debris 2 days later
72
Q
Wound Healing Proliferative phase
Time, Effector cells and Characteristics
A
- Day 3 to weeks after wound
- Fibroblasts, myofibroblasts, endothelial cells, keratinocytes and macrophages
- Deposition of granulation tissue and type III collagen, angiogenesis, epithelial cell proliferation, dissolution of clot and wound contraction
73
Q
Wound Healing Remodeling phase
Time, Effector cells and Characteristics
A
- 1 week to 6+ weeks after wound
- Fibroblasts
- Type III collagen is replaced by type I collagen, increase tensile strength of tissue
74
Q
Amyloidosis
Definition and Stains
A
- Abnormal aggregation of proteins (or their fragments) into beta-pleated linear sheets in the extracellular space leading to damage and apoptosis
- H and E stain it looks eosinophilic
- Congo red stain: it stains red
- Congo red stain with polarized light: two colors brown-yellow and apple green birefringence (the green color is diagnostic)
75
Q
Systemic Amyloidosis (Types)
A
- Primary amyloidosis
- Reactive systemic amyloidosis (secondary)
- Hemodialysis associated amyloidosis
76
Q
Localized Amyloidosis (Types)
A
- Senile cerebral amyloidosis
- Senile cardiac/systemic amyloidosis
- Endocrine type amyloidosis
77
Q
Primary Amyloidosis (Amyloid type and Associated conditions)
A
- Amyloid light chain (AL): whose fibrillary protein is made of kappa and lambda light chains
- Plasma cell disorders and multiple myeloma
78
Q
Reactive Systemic Amyloidosis (Secondary Amyloidosis)
Amyloid type and Associated conditions
A
- Amyloid associated amyloid (AA): whose fibrillary protein is serum amyloid A (SAA) [acute phase reactant that is produced by liver]
- Rheumatoid arthritis, SLE, IBD, spondyloarthtopathy, protracted infection (TB, bronchiectasis, and osteomyelitis), Crohn’s disease, Familial Mediterranean fever (FMF), and cancer
79
Q
Hemodialysis associated Amyloidosis
Amyloid type and Associated conditions
A
- Abeta-2M: whose fibrillary protein is beta-2 microglobulin
- End stage renal disease and/or long term dialysis
- May present as carpal tunnel syndrome
80
Q
Senile Cerebral Amyloidosis
Amyloid type and Associated conditions
A
- Abeta: whose fibrillary protein is beta amyloid precursor protein (beta APP). It is found in Alzheimer plaques and in cerebral vessels. Beta APP is located on Chrom. 21
- Alzheimer disease
81
Q
Senile Cardiac/Systemic Amyloidosis
Amyloid type and Associated conditions
A
- ATTR: whose fibrillary protein is transthyretin (produced by liver and is a transporter of thyroxin, retinal and retinol) which is deposited predominantly in cardiac ventricles
- Heart failure as a result of restrictive cardiomyopathy
Note: Isolated atrial amyloidosis is due to atrial natriuretic peptide (AANF) is common in normal aging
82
Q
Endocrine Type Amyloidosis
Amyloid type and Associated conditions
A
- Procalcitonin (ACal): in medullary thyroid carcinoma
- Prolactin (APro): in prolactinoma
- Amylin (AIAPP): in type 2 diabetes mellitus and pancreatic islet cell tumors
83
Q
Amyloidosis
Presentation
A
- Nephrotic syndrome and/or progressive renal failure
- Restrictive cardiomyopathy, low voltage EKG, arrhythmias, and congestive heart failure
- Hepatosplenomegaly
- Macroglossia (primarily in AL type) and malabsorption
84
Q
Amyloidosis
Diagnosis
A
Biopsy and Congo red stain with polarized light. Most common sites of biopsy are:
- Abdominal fat pad (most common one)
- Rectal mucosa
- Gingiva
- Tongue
85
Q
Amyloidosis
Treatment
A
- Melphalan (nitrogen mustard alkylating agent) followed by stem cell transplantation (only 20-25% of patients are eligible for stem cell transplantation)
- Melphalan and dexamethasone for AL patients who are ineligible to stem cell transplantation
- In AA type treat the underlying condition, and eprodisate (which slows renal impairment by inhibiting polymerization of amyloid fibrils)
- In ATTR liver transplantation is curative
86
Q
Lipofuscin
A
- Yellow brown pigment associated with normal aging
- Formed by oxidization and polymerization of autophagocytosed organellar membranes
- Deposits mainly in heart, colon, liver, kidney, and eyes
87
Q
Carbon Monoxide (CO) Poisoning (Source, Mechanism, Symptoms, Treatment)
A
- Auto emissions, home heaters, fires, and cigarette smoke
- Tissue hypoxia by decreasing oxygen delivery (shifting oxygen dissociation curve to left) and by inhibiting complex IV in ETC (same mechanism as CN)
- Increased carboxyhemoglobin concentration will cause bright “cherry-red” color of skin, mucous membranes and blood
- 10% is asymptomatic
- 30% headache and shortness of breath on exertion
- 50% loss of consciousness, convulsions and coma
- 60% death
- Rx: remove from source of exposure, 100% oxygen and if available, hyperbaric oxygen
88
Q
Mushroom Poisoning
Source, Symptoms, Treatment
A
- Amanita muscaria (Ibotenic acid [neurotoxin that acts as glutamate receptor agonist and a prodrug to muscimol] and muscimol [selective agonist of GABAa receptors with sedative-hypnotic and dissociative psychoactivity]) and Amanita phalloides (Amanitin [RNA polymerase inhibitor])
- Abdominal pain, vomiting, and diarrhea that may progress to fulminant hepatitis with extensive liver necrosis which leads to coma and death
- Rx: A. muscaria is rarely lethal and patients recover with supportive Rx. A. phalloides is treated with gastric decontamination by activated carbon or gastric lavage, supportive measures to treat dehydration, acidosis and electrolytes imbalance, High-dose continuous IV penicillin G, Silibinin (prevents amanitin uptake by liver cells and stimulates DNA-dependent RNA polymerases —> increase RNA polymerase synthesis), and liver transplantation
89
Q
Arsenic Poisoning (Mechanism, Acute poisoning symptoms, Chronic poisoning symptoms)
A
- Binds to disulfide groups of proteins and detected in hair and nails long after exposure
- Acute: hemorrhagic gastroenteritis, CNS toxicity with convulsions and coma, and “garlic-scented” breath
- Chronic: malaise, abdominal cramps, peripheral neuropathy and muscle weakness, skin changes (hyperpigmentation and dermatitis) with Mee’s lines on finger nails
90
Q
Lead Poisoning (Sources, Mechanism, Symptoms, Diagnosis, Treatment)
A
- Primarily affects children from lead pain (paint chips), lead plumbing, and leaded gasoline
- Demyelination of neurons in CNS for children and peripheral neurons in adults. Also decrease heme synthesis by inhibition of ferrochelatase and ALA dehydrase
- In children lethargy, somnolence, cognitive impairment and behavioral problem (DDx of ADHD), which may progress to mental retardation, cerebral edema and encephalopathy. In adults wrist or foot drop, abdominal pain (lead colic), renal tubular acidosis and renal failure, and lead lines on gingivodental line
- Dx: lead lines on x-ray on epiphyseal growth plates of long bones, sideroblastic anemia (microcytic anemia with basophilic stippling [due to inhibition of pyrimidine 5’ nucleotidase]), increased lead level in blood and increased free erythrocyte protoporphyrin
- Rx: stop exposure and treat with chelating agents (in children succimer [oral], also d-penicillamine [oral], EDTA and Dimercaprol (BAL) [both are injectable])
91
Q
Mercury Poisoning
Source, Symptoms, Treatment
A
- Eating big fishes like sharks and sword fish
- Neurotoxicity (intention tremors, dementia and delirium “mad as a hatter”) and nephrotoxicity (acute tubular acidosis)
- Rx: stop exposure and give chelating agents
92
Q
Cyanide Poisoning (Sources, Mechanism, Symptoms, Treatment)
A
- Firefighters exposed to smoke of burned polyesters
- Blocks respiration by binding to mitochondrial cytochrome oxidase (Complex IV), thereby acting as a systemic asphyxiant
- “Bitter almond-scented” breath
- Rx: Hydroxocobolamine (Rx of choice which is converted to cyanocobolamine [vitamin B12]) or Nitrites (makes metHb) then sodium thiosulfate to excrete it in urine
93
Q
Cigarette Smoking
Cardiovascular Complications
A
- Atherosclerosis
- Coronary artery disease and MI
- Peripheral vascular disease
- Aortic aneurysms
- Strokes
- Buerger disease
94
Q
Cigarette Smoking
Respiratory Complications
A
- Bronchogenic lung carcinoma
- Chronic bronchitis
- Emphysema (centriacenic)
- Asthma
- Increased pulmonary infections
95
Q
Cigarette Smoking
Complications in Women
A
- Early menopause
- Increased risk of postmenopausal osteoporosis
- In pregnancy there is increased risk of:
- Spontaneous abortions and stillbirths
- IUGR
- Sudden infant death syndrome (SIDS)
96
Q
Cigarette Smoking
Complications in Children of smokers
A
Increased risk of:
- Asthma
- Otitis media
- Upper respiratory tract infections
97
Q
Acute Alcohol (ethanol) Poisoning (Presentation)
A
All due to CNS depressant effect:
- Inebriation
- Coma
- Respiratory arrest
98
Q
Chronic Alcohol (ethanol) Poisoning (Presentation)
A
- Liver (fatty change, alcoholic hepatitis, and micronodular cirrhosis)
- Stomach (acute gastritis and Mallory-Weiss syndrome)
- Pancreas (acute or chronic pancreatitis)
- Blood (megaloblastic anemia)
- Heart (dilated cardiomyopathy)
- CNS (Wernicke-Korsakoff syndrome)
- Fetal alcohol syndrome
99
Q
Methanol Poisoning (Mechanism, Symptoms, Treatment)
A
- Metabolized by alcohol dehydrogenase to formaldehyde and formic acid
- Blindness (necrosis of retinal ganglion cells) and inebriation, coma and death
- Rx: Fomepizole (DOC) and ethyl alcohol (ethanol)
