Week 5 Flashcards
(104 cards)
1
Q
4 types of tissue in human body
A
Connective, Muscle, nerve, epithelium
2
Q
Epithelial cell functions
A
Protection, transportation, glandular secretion, sensation.
3
Q
Polarity of epithelial cells
A
Different characteristics of different sides of epithelial cells. Apical, basal, lateral sides have different proteins and organelles.
4
Q
Simple epithelium vs. stratified vs. pseudo stratified
A
Single layer of epithelial cells vs multiple layers Pseudo stratified has cells that are all attached to basal membrane, but not all reach surface.
5
Q
Squamous, cuboidal, columnar, transitional epithelial cells
A
Squamous = smooth and flat with flattened nuclei Cuboidal = roughly similar dimensions on all sides, spherical nuclei Columnar = elongated cells with, elongated nuclei Transitional= specialized stratified epithelium with rounded, dispensable cells at top. Found in lower urinary tract.
6
Q
Attributes and locations of: Simple squamous
A
Large surface area and thin diffusion distance are optimal for exchange surfaces. Alveoli, Bowman’s capsule, blood vessels, mesothelium in body cavities
7
Q
Attributes and locations of: Simple cuboidal
A
Protection, absorption, secretion. Typically found in ducts of exocrine glands, kidney tubules, thyroid follicles
8
Q
Attributes and locations of: Simple columnar
A
Absorption and secretion. Stomach cells, small intestines/colon, gallbladder
9
Q
Attributes and locations of: Stratified squamous
A
Many flat layers produce lubrication and protection via cells that can slough off and be quickly replaced. Can exhibit keratinization (thickening of cells at top) Epidermis, oral cavity and esophagus, vagina
10
Q
Attributes and locations of: Stratified cuboidal
A
Protection/conduit Large ducts of exocrine glands (salivary, sweat, mammary) and anorectal junction
11
Q
Attributes and locations of: Stratified columnar
A
Protection and conduit of largest exocrine ducts and the anorectal junction
12
Q
Attributes and locations of: Transitional epithelium
A
Distensible cells used for protection in lower urinary tract.
13
Q
Exocrine vs endocrine
A
Exocrine secrete into ducts while endocrine secrete through basal surface/connective tissue into blood stream
14
Q
Exocrine methods of secretion Endocrine
A
Exocrine secrete from apical side Merocrine = exocytosis Apocrine= budding Holocrine= lysis of cell Endocrine all secret via exocytosis through basal side
15
Q
Serous vs mucous exocrine secretions
A
Serous are thin and watery, typically for flow. Digestive enzymes Mucous are viscous and slimy because of high concentration of saccharides.
16
Q
Appearance of mucous producing cells on histology slide
A
Cytoplasm appears to be empty
17
Q
Goblet cells
A
A unicellular exocrine gland Mucin producing cells for protection of GI and respiratory tracts.
18
Q
Multicellular exocrine glands
A
Ducts and glands. Simple tubular glands = large intestine Simple coiled tubular = sweat gland Compound acinar = pancreas (exocrine)
19
Q
Apical domain contents
A
Rich in enzymes, receptors, ion channels, carrier proteins and structures such as cilia and microvilli.
20
Q
Microvilli
A
Finger like extensions of the plasma membrane and cytoplasm. That increase exchange area in places like the intestinal brush border and striated border. Actin filament core anchored to web in cell. Diameter of microvilli can change via actin contraction to increase/decrease permeability.
21
Q
Sterocilia
A
Immobile microvilli that serve as mechanoreceptors in inner ear, vas deferents, epididymis
22
Q
Cilia
A
Microtubule core moved by dynein (ATP dependent) arms in 9+2 formation (motile only). Can be both motile and non-motile. Nodal cilia are motile embryonic cilia that are responsible for L/R asymmetry of organs.
23
Q
Kartagener syndrome.
A
Autosomal recessive, motile cilia defect (loss of dynein arms) leads to uncoordinated betting of cilia. Poor mucociliary clearance-> chronic bronchitis, sinusitis, hearing and smell loss. Bronchiectasis and pneumonia. Immotile sperm, immotile fallopian cilia -> infertility Impaired nodal cilia -> situs inversus ( reversed organs)
24
Q
Primary Cilia and ADPKD
A
Immmotile 9+0 arrangement Polycystin 1 and 2 proteins- cilia passively bend in fluid flow to allow Ca2+ influx through protein channels Autosomal dominant polycystic kidney disease- mutations in polycystin proteins lead to cystic organ especially kidney
25
Cadherin
Calcium dependent adhesion molecules, form homodimers. Catenins link actin and cadherins. Maintain cell-cell interactions and loss of cadherins can lead to invasiveness and metastasis of cancer cells.
26
integrins
Heterodimers made of alpha and beta chains. Calcium independent. Important for cell-cell and cel-ECM binding. Can facilitate movement through ECM. Attachment of WBC
27
Zone Occludens
Tight junctions. Most apical junction type, barrier prevents paracellular transport. Occludin and Claudia are main two proteins
28
Zone adherens
Intermediate junctions. Further anchoring of cells, forms belt around cell. Made up of actin and Cadherin-catering complexes.
29
Macula adherens
Desmosomes. Spot welds in cells, help resist shearing of cells. Pathology of these leads to sharing/blistering. Calcium dependent proteins.
30
Gap junctions
Made of connectors made of connection. Allow for rapid intercellular communication
31
Basement membrane- structure, Attachment to epithelial cells and role in cancer.
Two regions- sheet like basal lamina and reticular lamina beneath. Attached to epithelial cells via Hemidesmosomes made of BP230, laminin5, type 4 collagen Attached to ECM via Integrins Benign tumors do not penetrate this region. Penetration is a sign of malignancy.
32
Pemphigus vulgaris
Autoimmune (IgG) attack of desmosomes (DG1 and DG3) Results in flaccid blisters on skin and oral mucosa. Hemidesmosomes remain intact. Immunofluorescence would highlight antibodies on side of cell.
33
Bulbous pemphigoid
Autoimmune (IgG) attack of BP230 in Hemidesmosomes. Tense blisters that do not rupture easily. Separation of epidermis from dermis, but epidermis remains intact (intact desmosomes). Immunofluorescence would highlight antibodies along basement membrane (basal side)
34
Dystrophic epidermolysis bullosa
Inherited collagen 7 defect. Results in mutated basal domain and separation of epidermis and dermis. Ongoing inflammation
35
Atrophy causes Demand, oxygen, trophic factors, chronic issues.
Decreased functional demand - typical in muscle/casting Hypoxia-ischemia, atherosclerosis (acute hypoxia results in cell death not atrophy) Malnutrition- anorexia or starvation Decreased trophic factors- low estrogen in endometrium, denervation(palsy) Persistent cell injury (inflammation, pressure, disease, aging) Chronic pressure - hydrocephaly, bed sores Chronic disease-chachexia
36
Cachexia- symptoms mechanisms and causes.
Atrophy of skeletal muscle from protein degradation. Negative nitrogen balance regardless of nutritional intake Induction of proteasome function and autophagy by cytokines (IL-6, TNF-alpha, PIF) during chronic disease such as cancer, aids, TB
37
Hypoplasia and Aplasia
Hypoplasia- underdeveloped tissue/organ. Reduced cell numbers Aplasia-absence of tissue or organ. Failure to develop at all.
38
Hypertrophy
Results from increased functional demand or trophic factors. Often accompanied by hyperplasia in cells that re able to proliferate.
39
Hypertrophy of heart
From hypertension or exercise. Exhibits larger cells with increased nuclear size.
40
Smooth muscle appearance- normal vs. hypertrophy
Normal smooth muscle will have elongated nuclei that are very close, on top of one another. No clear cell border. Hypertrophy has a recognizable border with more distant nuclei.
41
Mechanisms of hypertrophy
Mechanoreceptors that respond to stretch, receptors that respond to growth factors/agonists. Alters gene expression and can reinduce fetal myosin genes as well as atrial nature tic factor.
42
Free radicals (ROS) names and pathways
Superoxide anion (O2-) Hydroxyl radical (OH.) Hydroxyl ion (OH-) NO Peroxynitrite Oxygen can have electrons added by oxidases to form H2O2 or superoxide. Superoxide can be made into H2O2 by superoxide dismutase Hydroxyl radical can be made by gamm irradiation of water or Fenton reaction of peroxide (Fe2+-\>Fe3+)
43
ROS from mitochondria
ETC (oxphos) in mitochon results in superoxide and hydroxyl radical. Mostly from complex I and Complex III.
44
ROS from peroxisome
Beta oxidation of fatty acids, amino acid catabolism, synth of bile acids, synth of plasmalogens Make peroxide and superoxide.
45
ROS from NADPH oxidase Chronic granulomatous disease
In lysosomes, neutrophils, macrophages, monocytes, many others. 2 membrane proteins and 3 cytosolic proteins that must complex together to form NADPH oxidase. Replenishes NADP+ by creating superoxide Over 450 possible mutations that create the broad disease category of chronic granulomatous disease. Result is chronic infections in kids
46
Xanthine oxidase as source of ROS
Hypoxanthine-\>xanthine-\> uric acid Xanthine oxidase creates peroxide and superoxide
47
Oxidative stress (low and high)
High ROS can directly damage or kill cells low ROS can stimulate proliferation, damage lipids/proteins/DNA, or activate cellular pathways
48
Reperfusion injury
Reperfusion after an ischemic attack can cause temporary overload of ROS
49
Lipid peroxidation
Radical pulls off hydrogen from unsaturated lipid next to double bond to form lipid radical. This can propagate in a radical chain reaction (lipid radical attaches to oxygen then pulls H from another lipid) or terminate with two lipid radicals bonding. Can alter fluidity, permeability, and function of membrane components. Products can cross link with proteins, disrupt signaling, cause direct toxicity.
50
Protein fragmentation with ROS
Can cause disulfide linkages, excision of protein strands. Can cause loss of function in proteins and alteration of secondary and tertiary structure. Increased susceptibility to proteolysis.
51
DNA oxidation by ROS
Cause over 30 different base modifications. Mostly on thymidine and guanine residues. Cause of mutations and initiation of cancer. Repair can deplete energy reserves, induction of error prone polymerase.
52
Pro-oxidants
Induce oxidative stress by either promoting ROS formation or inhibiting antioxidants.
53
Preventative antioxidants
Aspirin, ibuprofen (anti-inflammatories) Metal chelators Enzyme inhibitors (nitric oxide synthase, xanthine oxidase, NADPH oxidase)
54
Antioxidants
SOD, glutathione peroxidase, albumin, Vitamin C, Vitamin E, polyphenols, carotenoids
55
Catalase and glutathione peroxidase
Catalase H2O2-\> H2O Glutathione peroxidase reduces peroxide by oxidizing 2 glutathiones to form a disulfide bond. Glutathione is replenished by glutathione reductase which gets electrons from NADPH. NADPH made from glucose-6P dehydrogenase in PPP
56
Acid dyes
Carry a net negative charge and bind with cationic or eosinophilic tissue. Most common stain is eosin Broad base stain that attaches to mitochondria, secretory granules, collagen fibers, cytoplasm, basement membrane, ECM.
57
Basic dyes
Carry a net positive charge, bind with anionic or basophilic tissue. Hematoxylin is most common, not a true basic dye but acts like one. Binds to negative charge of DNA, RNA, coarboxyl groups of proteins, sulfate groups in cartilage.
58
H and E stain
Most common combo
59
Epithelial tissue
Lines body surfaces, ducts, hollow organs, cavities, forms glands. Very little or no ECM. Aggregated polyhedral cells with specialized junctions. Nourished by underlying basement membrane. A vascular but innervated. Rapid regeneration is possible.
60
Connective tissue
Protect and support. Several cell types often present in one area, spaced out with lots of ECM Most abundant tissue type in body. Degrees of vascularity run the gamut. Bone is highly vascular while cartilage is a vascular. May be loose, reticular, dense, aadipose, blood, etc.
61
Muscle tissue
Contractile cells for ATP powered movement. Moderate amount of ECM
62
Nervous tissue
Detects changes in environment and generates AP. Vital in homeostasis No ECM and long intertwined processes
63
Mesenchymal cells
Stem cells that form many different types of cells including connective tissue. Flat elongated and undifferentiated.
64
ECM composition
Extra cellular matrix. Formed from protein fibers (mostly collagen) and ground substance Ground substance is an unstructured, amorphous mass of proteoglycans, glycoproteins, etc. hydrophilic, and many possible consistencies (fluid to calcified)
65
Etiology
Initiating event or agent of a disease. Often associated with disease related risk factors
66
Pathogenesis
Sequence of cellular, biochemical, molecular events that follow exposure of cell/tissue/organ to an injury. Often presents as cumulative damage leading to an abnormal state.
67
Common cell injury modes
Hypoxia/anoxia due to ischemia, chemical, or O2 deprivation Physical injury- trauma, radiation, temperature, electricity Chemicals- toxic levels of innocuous substances, poisons/toxins Infectious agents Autoimmunity Mal/hypernutrition Genetic mutations/abnormalities
68
Hyperplasia
Increase in number of cells. Only certain cells can do this. Must be able to enter cell cycle. Often occurs with hypertrophy (uterus). Incapable cells will be hypertrophy alone (skeletal, cardiac muscle( May progress to dysphasia/cancer
69
Metaplasia
New/increased stress or chronic irritation. Changes cell type in a given area. Most commonly one type of epithelium changes to another that is better able to cope with new stress. In theory reversible is stress is removed. May also progress to dysphasia/cancer
70
Barrett’s esophagus
Non-keratinized squamous epithelium of esophagus converted to non-ciliated mucin producing epithelium of stomach. generally in response to smoking or acid reflux.
71
Dysplasia
Disordered cellular growth. Can arise from longstanding hyperplasia, metaplasia. Typically refers to potentially pre-cancerous cells. Progression to cancer or regression to normal cells is thought to be dependent on continuation/removal of stress.
72
Reversible cell injury
Functional and morphological changes due to mild transient stress that can be reversed if stress is removed.
73
Cell death
Response to strong/persistent damaging stimulus. Necrosis/apoptosis.
74
Selective vulnerability
Some cells are more susceptible to certain kinds of stress.
75
MOrphology changes from cell stress. Swelling and fatty change.
Cell swelling, cell can’t maintain osmotic homeostasis due to a lack of ATP. Fatty change- appearance of lipid vacuoles in cells dependent upon lipid metabolism. Toxic, metabolic and hypoxic injury
76
Most common cell components affected by cell injury.
Mitochondria, membranes, DNA, protein synth/transport.
77
Cellular mechanisms of injury
ATP depletion/decreased synth Mitochon damage Loss of calcium homeostasis Oxidative stress (ROS accumulation) Loss of membrane selectivity DNA/protein damage
78
ATP depletion and cell injury
Hypoxic and toxic injuries that lead to mitochondrial damage. resulting ATP depletion leads to lactic acid productions and drop in cell ph. Affects transport, enzyme efficiency and denaturation. ATP depletion also affects protein synth, membrane transport/maintenance.
79
Mitochondrial damage and cell injury
Common in hypoxia/ischemia, toxin exposure. May also be damaged by increase in Ca2+, ROS Results in lack of ATP, increase in ROS, apoptosis or necrosis.
80
Loss of calcium homeostasis and cell injury
Ca storage in mitochondria, SER Ca is released from storage by ischemia, hypoxia, toxins. Cytosolic Ca increases mitochondrial permeability- Failure of ATP production, activation of new pathways, activation of caspases(apoptosis)
81
Oxidative stress in cell injury
ROS accumulation can modify or break lipids/membrane, proteins/enzymes, nucleic acids/DNA, etc. Injury occurs when production increases or capacity for scavenging ROS decreases.
82
Membrane permeability and cell damage.
Loss of membrane selectivity can lead to decreased ATP production(mitochon membrane), lost osmotic balance(plasma membrane), lysosome contents in cytosol(lysosomal) Can occur through ROS damage, decreased ATP production (active transport, lipid and protein synth), cytoskeleton abnormalities from protease activity.
83
DNA/protein damage in cell injury
If DNA repair mechanisms are overwhelmed or impaired, DNA damage will accumulate and apoptosis will initiate. Can also occur with protein misfolding.
84
Two consistent phenomena of irreversibility
Membrane damage (plasma, lysosomal, mitochon) or irreversible mitochon damage.
85
Necrosis vs. apoptosis
Necrosis- Death of large groups of cells, usually followed by inflammation. Always pathological Apoptosis- programmed cell death, may be pathological or physiologic. Happens to single cells with no inflammation, cell shrinks and chromatin is condensed before blebbing and phagocytosis.
86
87
Mitochondrial role in aging
Damage on mitochondrial RNA, DNA, ribosomes accumulates from ROS with lack of repair mechanisms. Mitochondria become less functional over time.
88
Cytochrome C Oxidase
COX, complex IV in ETC chain site of toxicity for CN, CO, and Azide. CN and azide bind to Fe3+, CO binds to Fe2+
89
Ischemic injury of mitochondria
Lack of oxygen from blood backs up ETC/Kreb’s. Lowers ATP production -\> impairment of membrane ion pumps -\> net ion movement into cell -\> swelling Build up of lactate -\> lower ph -\> sodium/ H+ antiportation-\> sodium movement into cell -\> further swelling Low ATP production -\> failure of Ca2+ pumps -\> influx of calcium -\> Ca induced cell injury Swelling leads to cellular vacuolation and hydropic degeneration
90
Ca induced cell injury
Ca comes in from ECF or stores in mitochondria/SER. Induces proteases, endonucleases, phospholipases, ATPases. All of which result in increased cell damage and activation of apoptosis and potential necrosis.
91
Steatosis
Fatty liver disease, too much synth or inadequate packaging or removal of triglycerides in hepatocytes. Results in fast vacuoles. Often seen in diabetes, hypoxia/toxins/drugs (alcohol), protein energy malnutrition, metabolic syndrome . Appears as enlarged and yellow liver, on histologic slides, many fatty vacuoles will be present. Can also occur in muscle, heart, kidney (fatty change)
92
Mechanisms of intracellular accumulations
Abnormal metabolism(impaired removal/packaging), impaired protein folding, inherited enzyme deficiencies, deposition/ accumulation of exogenous substance
93
Accumulation of cholesterol
Results in foamy macrophages. Seen in atherosclerosis, and xanthine (bubbles under skin around joints.
94
Enzyme deficiency, intracellular accumulations (lysosome roles)
Lysosomal storage diseases are a common form. Normal digestion results in small molecules that can diffuse out of cells. Abnormal digestion results in accumultion of byproducts, often to toxic levels.
95
Gaucher disease
SOhingolipid storage disease. “Crinkled tissue paper appearance on histology
96
Common mechanisms/diseases of protein accumulation
Excess protein reabsorption in nephron tubules Excessive synth of antibodies in ER and Golgi Apparatus of plasma cells Alpha1-antitrypsin gene mutation resulting in misfolding and defective transport/secretion. Aggregation of cytoskeletal filaments- keratin in alcoholic liver disease. Amyloid plaques in Alzheimer’s
97
Alpha 1 antitrypsin
A1AT accumulates in hepatocytes due to misfolding from gene mutation. Red eosinophilic globules in ER of cell. Inability to inactivate neutrophil proteases resulting in breakdown of lung tissue and emphysema
98
Mallory bodies
Aggregates of cytoskeletal proteins (keratin) in alcoholic liver disease. Pink eosinophilic aggregates
99
GLycogen accumulation in cells
Diabetes can cause accumulation in kidney tubules, liver, heart. Glycogen storage defects due to deficiency in enzymatic degradation. Glycogen appears pale on histologic section
100
Lipofuscin
Wear and tear pigment from build up of lipoproteins over time. Sits in lysosome undegraded. Normal in aging individuals Golden brown pigment granules in cytoplasm of cardiac muscles, skeletal muscles, or neurons
101
He onside run
Yellow brown pigment , Aggregate of ferritin micelles (cellular storage form of iron). cumulates from any increase of iron levels including transfusions nd hemolytic anemia. Iron is blue on Prussian blue stain
102
Anthracosis
Black exogenous carbon pigment. Can’t be metabolized and accumulates whenever exposed.
103
Tattoos
Exogenous pigments that accumulate in dermis.
104
Histology of accumulation summary Protein, glycogen, fat, cholesterol, lysosome storage, lipofuscin, hemp Sid Erin, carbon
Proteins= pink globules/aggregates in HandE stains. Glycogen or fat= clear vesicles Oil red o for triglyceride accum. PAS for glycogen storage disease Cholesterol/lysosomal storage/glycogen storage = foamy macrophage . Lipofuscin = golden brown pigment granulesin cardiac, muscle, neuron tissues Hemosiderin = coarse yellow brown pigment in cells. Proved by Prussian blue Carbon= black pigment in cells.
