1
Q
tissue and the types
A
group of cells within a similar structure and function
-epithelial, nervous, muscle and connective
2
Q
atrophy vs. hypertrophy
A
decrease in cellular size
increase in cellular size
3
Q
hyperplasia
A
increase number of cells
4
Q
dysplasia
A
deranged cellular growth
-abnormal changes
5
Q
metaplasia
A
replacement of 1 type of cell with another
response to chronic irritation
6
Q
cellular injury
A
cells are unable to maintain homeostasis
7
Q
hypoxic
A
most common cause of cell injury
results from …
low o2, low number of hemoglobin, low production of RBC
poisoning of oxidative enzymes
8
Q
ischemia
A
low blood flow to a region
most common cause of hypoxia
9
Q
ischemia-reperfusion injury
A
additional injury caused by restoration of blood flow and o2
mechanisms/caused by oxidative stress, inflammation, increase intracellular calcium, complement activation
10
Q
anoxia
A
complete lack of o2
cellular response: -decrease ATP causing stop of Na/K pump and Na/Ca exchange
-cellular swelling
-vacuolation
reperfusion injury after anoxia can cause further damage
11
Q
Oxidative stress
A
an imbalance of free radicals and reactive o2 species (ROS) that leads to cell damage
-produced by reperfusion
-has unpaired electron
-damages lipid peroxidation, alters proteins and DNA, mitochondria
12
Q
xenobiotic
A
any foreign substance that can harm our cells
chemical injury
-CO, carbon tetrachloride, lead
13
Q
chemical agents
A
over the count and prescribed meds
-leading cause of child poisoning
-can cause direct damage or hypersensitivity reactions
14
Q
direct damage
A
chemicals combining with critical molecular substance
15
Q
hypersensitivity reactions
A
occurs when immune system mistakes normal cells for foreign cells
-range from mild skin rash to immune-mediated organ failure
16
Q
blunt-force injuries
A
caused by impact without skin break
-results in tearing, shearing or crushing of internal tissues
17
Q
Contusion
A
bruises
damaged BV/ bleeding in tissues
18
Q
lacerations
A
irregular tears in skin or underlying tissue
may involve muscles or vessels
19
Q
fractures
A
can be closed or open/compound
20
Q
sharp-force injuries
A
incised (sharp object drawn across skin), stab, puncture (needles) and chopping wound
21
Q
gunshot wounds
A
entrance wound smaller than exit
22
Q
asphyxia injuries
A
caused by cell not receive or use o2
-suffocation, strangulation, chemical asphyxiants and drowning
23
Q
infectious injury
A
pathogenicity of microorganisms
disease producing potential
-based on invasion, toxin production and production of hypersensitivity reactions
24
Q
types of toxins and define
A
exotoxin: protein secreted by bacteria in surrounding environment
endotoxin: components of bacteria cell wall
25
phagocytic cells
ex. macrophages and neutrophils
-crucial for immune response
-release enzymes and ROS to kill pathogens
26
immune and inflammatory substances
too much can cause harm
-histamines >vasodilation, increase permeability, can leas to excess inflammation
-antibodies> neutralize pathogen
-lymphokines
-protease
27
cellular accumulations/infiltration
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produced by normal and abnormal cellular (endogenous -in cell, exogenous out of cell) substances
28
4 mechanism of abnormal accumulation inside cell
-insufficient removal of normal substance bc altered packaging and transport
-results from a mutated gene bc a defect in protein folding
-lack of enzymes
-ingestion of non-digestible materials
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necrosis
sum of cellular changes after cell death and process of cellular autodigestion
30
coagulative necrosis
most common
-affected tissues is firm and pale
-still outline of cell but internal structures are damaged
ex. after myocardial infarction
31
liquefactive necrosis
affected tissues become a liquid viscous mass
common in brain
-tissues becomes soft bc hydrolytic enzymes
ex. result of bacterial enzymes
32
caseous necrosis
granular, cheese look
common with tuberculous pulmonary infection
combines coagulative and liquefactive necrosis
33
fat necrosis
inflammatory cells attack damaged fat cells and lipase is released and breaks down triglycerides into fatty acid
-seen with chalky white substance >fatty acids + glycerol + Ca
34
gangrenous necrosis
tissue death from severe hypoxic injury
dry gangrene caused by chronic ischemia
wet gangrene caused by sudden interruption of blood supply with bacterial infection
subtype: gas gangrene > caused by infection with anaerobic bacteria
35
apoptosis
programmed cellular death unlike necrosis controlled
36
physical reasons for apoptosis
development processes
immune system
37
pathological reasons for apoptosis
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excessive apoptosis
-insufficient apoptosis
-infections
-misfolded proteins
38
autophagy
process where cells degrade and recycle their cytoplasmic content, helps cells adapt to stress
declines with age
39
autophagy mechanisms
cytoplasmic content are enveloped by an autophagosome then fused with a lysosome for degradation
40
cellular aging
atrophy, loss of cells
41
tissues and systemic aging
increase collogen cross-linking, progression stiffness
-sarcopenia >age related loss of muscle mass
42
somatic death
death of entire person
43
postmortem changes
algor mortis
livor mortis
rigor mortis
postmortem autolysis
44
algor mortis
process of body cooling after death
45
livor mortis
settling of blood due to gravity
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rigor mortis
stiffness of muscles after death
47
postmortem autolysis
self digestion of cells by their own enzymes which forms gases and fluids
48
cancer
disease where abnormal cells divide without control and can invade other tissues
49
tumour
new growth neoplasm
50
benign tumours
-grow slowly
well-defined capsule
-non-invasive
-low mitotic index
-dont metastasize (spread)
-can become cancerous
ex.
meningioma (in meninges)
lipoma (fat tissue)
leiomyoma (smooth muscle tissue
51
malignant tumours
-grow fast
-not encapsulated
-invasive
-high mitotic index
-metastasize (spread)
ex. carcinoma (epithelial tissues)
adenocarcinoma (ductal or glandular tissue)
sarcoma (mesenchymal tissue)
lymphoma (lymphatic tissue
leukemia (blood forming cells(
52
CIS
carcinoma in situ
-carcinoma that hasn't broken through basement membrane or haven't invaded surrounding tissue
53
biology of cancer cells
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multiple mutations are needed before cancer can develop
clonal proliferation/expansion: bc of a mutation, a cell gets characteristics that allow it to have a selective advantage
-increase growth rate or decrease apoptosis
54
transformation of normal cells to cancer cells
decreased need for growth factors (external signal) to multiple
-ignore of contact inhibition
-cancer cells don't attach to matrix allowing them to spread
-cancer cells don't have a dividing limit > activate telomerase making telomeres longer
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contact inhibition
normal cells stops growing when they touch neighboring cells
56
proto-oncogenes
normal genes that direct protein synthesis and cellular growth
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tumour-suppressor genes/anti-oncogenes
encode protein that negatively regulation proliferation
58
oncogenes
mutant proto-oncogenes that increase cell growth
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oncogene activation
caused by point mutation in RAS gene converts it regulated to unregulated
caused by translocation
-Burkitt lymphomas >over production MYC protein
-Chronic myeloid leukemia >translocation of chromosome 9 and 22
-gene amplification > multiple copies of the gene/overexpression of the protein (increase amount of proteins)
60
evading growth suppressors
Mutation (inactivation) of tumour-suppressor genes - allows unregulated cellular
growth
ex. Retinoblastoma (RB) gene, Tumour protein p53 (TP53)
61
Genomic instability
increase tendency for genomic mutation during life cycle
-increase risk for cancer
-altered promoter region of genes> abnormal or silencing expression of genes
-chromosome instability (increase number of malignant cells)
62
caretaker genes
encode for proteins that repair damaged DNA
-maintain genomic stability
ex. BRAC 1
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cancer immortality
cancer cells activate telomerase to make telomeres longer
-normally, telomeres block cell division and becomes shorter after each division
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angiogenesis and cancer cells
growth of new blood vessel
-cancer cells secrete angiogenic factor to grow BV
-vascular endothelial growth factor
-platelet-derived GF
-basic fibroblast GF
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Warburg effect
cancer cells use glycolysis to generate energy when o2 is available for growth, normal cells use oxidative phosphorylation
-activated by oncogeneses and mutant tumour suppressor
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reverse Warburg effect
cancer cell influence normal cells to switch aerobic glycolysis
67
inflammation and cancer
chromic inflammation is a factor in developing cancer
-cytokine is released from inflammatory cells (helps cell growth)
-Helicobacter pylori: associated with peptic ulcer disease, stomach carcinoma, mucosa-associated lymphoid tissue lymphomas
68
immune system and cancer
immunosuppression fosters cancer
-non-Hodgkin's lymphoma (10x the risk if immunocompromised)
-Kaposi sarcoma (1000x)
increase resistance of tumour to chemotherapy and radiotherapy
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viruses linked to cancer
Hep B and C
Epstein-Barr virus
Kaposi sarcoma herpesvirus
human papillomavirus (HPV)
human t-cell lymphotropic virus type 1
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metastasis
process of cancer spreading from origin site
2 routes
-direct invasion/local spread
-metastases to distant organs
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Epithelial-Mesenchymal transition
bio process to metastatic cancer cells
epithelial characteristics lost (increase migratory capacity/move more, increase resistance to apoptosis, dedifferentiated stem cell like state)
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local spread
mitotic rate is greater than cell death
invading neighboring tissues
cancer cell secret lytic enyzmes to breakdown extracellular matrix to decrease cell-cell adhesion
increase motility
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distant metastasis
spread through lymphatics and blood
cancer can remain dormant in organs for a long time before they start growing
ex. breast cancer tends to spread to bones
lymphomas >spleen
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paraneoplastic syndromes
maybe earliest symptom of cancer
-triggered by substances produced by tumour
irreversible
75
mechanism of pain bc of cancer
obstruction
invasion of sensitive structures
stretching of visceral surfaces
tissue obstruction
inflammation/infection
76
cachexia
most severe malnutrition
includes anorexia, weight loss, anemia, altered metabolism
77
anemia
decrease RBC or decrease hemoglobin
impaired production of erythrocytes, blood loss
mechanisms: chronic bleeding, malnutrition, medial therapy, decrease erythropoietin
78
leukopenia and thrombocytopenia
low WBC and platelets
caused by direct tumour invasion in bone marrow
-chemotherapy meds are toxic to bone marrow
infection increase bc low neutrophil and lymphocyte
79
hair and skin manifestations of cancer
alopecia from chemo
skin breaks down and dry
80
Clinical manifestation of cancer
paraneoplastic syndromes
pain
fatigue (most common)
cachexia
anemia
leukopenia and thrombocytopenia
81
gi manifestations of cancer
oral ulcer
diarrhea and malabsorption
therapy-induced nausea
82
ways to diagnose cancer
blood work, imaging and biopsy
83
stages of cancer *
stage 1: early stage
-small invasive mass
-no spread to other tissues
stage 2: localized
-cancer affects nearby tissues
-may grow in size
spread to lymph nodes near the mass
stage 3: regional spread
-affect more surrounding tissue
-grows
-spread to distant lymph nodes
stage 4: distant spread
-spread to other tissues and organs beyond region of origin
84
WHO TNM system ***
tumor size, lymph node status, metastasis
T-1: 0-2cm
T-2: 2-5cm
T-3: >5cm
T-4: tumor has broken through skin or attached to chest wall
N-0: surgeon can't feel any nodes
N-1: surgeon can feel swollen nodes
N-2: patient feels that nodes are swollen and lumpy
N-3: swollen node located near collarbone
M-0:tested nodes are cancer free
M-1: tested nodes show cancer cells or micro metastasis
85
tumour markers
substance produced by cancer cells that are found on or in tumour cells, blood, CSF or urine
used to:
○ Screen and identify individuals at high risk for cancer
○ Diagnose specific types of tumours
○ Observe clinical course of cancer
Problem: false positives and negatives
86
examples of tumour markers
hormones, antigens, enzymes, antibodies and genes
87
cancer treatment
surgery
-biopsy for diagnosis and staging
radiation
chemo
88
radiation therapy
goal is eradicate cancer without excessive toxicity
-damages cancer cell's DNA
89
chemotherapy
targets quick dividing cells
induction chem: shrinkage or disappearance of tumours
adjuvant chem: eliminate micrometastases (small cancer cells) after surgery
neoadjuvant therapy: given before localized treatment to shrink tumour
90
immunotherapy
vaccines against oncogenic viruses for prevention
therapeutic vaccines (little success)
allogeneic cancer cell vaccines (uses cc from other patient to stimulate the immune system)
91
cancer treatment mechanisms
-inactivate oncogenes
-affect cell metabolism
-neutralize cytokines
-block angiogensis
-induce apoptosis
92
childhood cancer
common leukemia, sarcoma and embryonic tumours
93
embryonic tumours
originate during intrauterine life
-immature embryonic tissue unable to mature
'blast'
ex. neuroblastoma
94
etiology of childhood cancer
often linked to genetic abnormalities
chromosome abnormalities (aneuploid, amplifications, deletion, translocation and fragility)
congenital syndromes (wilms tumour and ureogenital abnormalities, down syndrome and leukemia)
oncogenes and tumor-suppressor genes
95
prognosis for childhood cancer
70% are cured
96
cell surface changes in cancer
express abnormal antigens, change their adhesion molecules and secrete enzymes that degrade surrounding matrix
-growth factor receptors are overexpressed
97
role of stem cells in cancer
within tumour cancer stem cells drives growth
-self-renew and generate diverse cell types
resistant to therapy
98
autonomy
ability of cancer cells to grow independently
-cancer cells produce their own growth pathways and ignore inhibitory signals
99
anaplasia
loss of differentiation and normal cell structure
100
Common causes of cellular injury
Hypoxia
Ischemia
Ischemia-reperfusion injury
Anoxia
Oxidative stress
Infection
Chemical exposure
101
Types of cellular death
Necrosis and apoptosis
102
clinical signs of somatic death
Body is cool, blood is settled, muscles are stiff and gases and fluids are being formed
103
impact of aging and degenerative cellular changes on tissue integrity and patient recovery
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Autophagy declines with age
Loss of cells
Increase collagen crosslinking, progressive stiffness
Sarcopenia
Heal slower
104
molecular mechanisms underlying cancer development
-Oncogenes
-Tumor suppressor genes
-Activation of telomerase making telomerase longer
-Chronic inflammation: cytokine is released from inflammatory cells (helps cell growth)
105
major clinical manifestations of cancer
lumps, Fatigue, cachexia, anemia, leukopenia, thrombocytopenia, malabsorption
106
innate immunity
physical barriers (GI tract, cilia, skin)
epithelial cell-derived chemical barriers (secretes saliva, tears, sweat) , normal microbiome
107
fibrinous exudate
thick clotted exudate
advanced inflammation
108
purulent exudate
pus
indicates a bacterial infection
109
systemic manifestations of acute inflammation
fever
leukocytosis
increase plasma protein synthesis
110
fever
caused by exogenous and endogenous pyrogens (acts directly on hypothalamus
111
leukocytosis
increase number of circulating leukocytes
112
lab tests for inflammation
fibrinogen
erythrocyte sedimentation rate
c reactive protein
113
chronic inflammation
longer than 2 weeks
relates to unsuccessful acute inflammatory response
114
causes of chronic inflammation
high lipid and wax content of a microorganism
survive inside macrophage
toxins
chemical or physical irritants
115
characteristics of chronic inflammation
dense infiltration of lymphocytes and macrophages
granuloma formation
epithelioid cell formation
giant cell formation
116
parts of wound healing
resolution: injury returned to original structure and function
repair: replace destroyed tissue with scar
healing: filling wound, epithelization, contraction
117
primary intention healing
wounds heals with minimal tissue loss
118
secondary intention healing
wounds that need more tissue replacement
ex. open wound
119
wound healing phases
inflammation, proliferation, remodeling and maturation phase
120
inflammation phase
coagulation, infiltration of wound healing cells, angiogenesis
121
proliferation phase
granulation, epithelization, needs fibroblast proliferation, collagen formation and wound contraction
122
remodeling and maturation phase of healing
continuation of cell differentiation
form scar tissue
scar remodeling
123
dysfunctional wound healing
can be caused by..
-ischemia, excessive bleeding, excessive fibrin deposition, diabetes
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adaptive immunity
-destroys microorganisms that survived inflammation
inducible (activated by a pathogen)
long lived
has memory about previous pathogens
components: antigen and t and b cells
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humoral immunity
uses immunoglobulins (antibodies) which is produced by b cells
-binds to antigens on bacteria and viruses
produce memory cells
126
cellular immunity
uses T cells
kill target directly
produces memory cells
127
b cell development
production, proliferation and differentiation happens in bone marrow
travel to lymphoid tissue and resides there as immunocompetent cells
each cell responds to only 1 specific antigen
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t cell development
produced and developed in thymus
develops antigen-specific t cell receptors (TCRs)
travel to lymphoid tissues and resides there as mature immunocompetent cells
129
active vs. passive immunity
exposure to pathogen to gain immunity (vaccines, infection)
pre form antibodies that are transferred (maternal antibodies)
130
antigens
bind with antibodies or receptors on t and b cells
-not necessarily immunogens
-within or produced by pathogen
131
immunogens
induce antibodies production and t and be cells
all are antigens
132
haptens
too small to be immunogens
can become immunogens after combining with larger molecules
133
immunoglobulins
proteins produced by b cells
classes: IgG, A, M, D
134
immunoglobulin G
most abundant
gives most protection against infections
4 sub classes: IgG-1,2,3,4
135
immunoglobulin A
2 classes: IgA, IgA-2
IgA: found in blood
IgA-2 found in bodily secretions
136
immunoglobulin S
low concentration in blood
functions as a type of b cell antigen receptor
137
immunoglobulin M
largest
pentamer stabilized by a J chain
first antibody produce during primary response to a antigen
made early in neonatal life
138
Antigen-antibody binding
antigenic determinant/ epitope: area of antigen recognized by antigen
Antigen-binding site/paratope: matching part on antibody
antigen fits in binding site of antibody, held in place by noncovalent chemical interactions
139
antibody functions
direct:
neutralization of threat
agglutination/clump bacteria together
precipitation to form clumps
indirect:
inflammation, phagocytosis, complement
140
immunoglobulin E
least concentration in blood
mediator of many allergic responses
defender against parasite
protection from larger parasite by causing inflammatory reaction to attract eosinophils
common cause of allergies
Fc portions are bound to mast cells
141
clonal diversity
all necessary receptors specificities are produced for lymphocytes
happens in lymphoid organs
occurs in the fetus
clonal selection
-antigen processing and presentation
-complex cellular interactions
142
antigen processing and presentation
initiates when t and be cells interact with antigen
antigens are first processed then presented by antigen-processing cells
results differentiation of b cell into active antibody-producing cells (plasma cells)
differentiation of t cells into effector cells (ie. t-cytotoxic cells
143
primary response
initial exposure
patent period (b-cell differentiation occurs)
after 507days, IgM antibody is detected
IgG response is equal or less after the IgM response
144
secondary response
subsequent exposure
more rapid bc of memory cells
more antibodies are produced
IgM may be produced but more IgG produced
more effective
145
T-cell activation
t-cell receptors bind to antigen, antigen is being presented by antigen presenting cells to activate t-cells
once connected, t-cell kill foreign cells via cytoxic cells and activate cytokines for inflammatory or immune system help
146
cytokine storm
too many cytokine
147
T-helper cells
when activated, help B and T cells mature
facilitate and strengthens interaction between APCs and lymphocytes
subsets: TH1 help develop cell-mediated immunity to activate t-cells and macrophages
TH2 help develop humoral immunity
Diff bc cytokine production
148
neonatal immunity
fetus has sufficient IgM but limiting IgG and IgA responses
maternal antibodies protect fetus
149
aging's affect of immune function
low t cell activity and function bc thymus shrinks
low cytotoxic activity
150
factors influencing infection
-communicability (how easy a pathogen can spread ie. measles high)
-infectivity ( ability of pathogen to invade and multiply)
-virulence (capacity of pathogen to cause severe disease)
-pathogenicity (ability of pathogen to produce disease)
-portal of entry
toxigenicity
151
types of portal of entry
direct contact (phys. touch), inhalation, ingestion, bites
152
toxigenicity
ability of a pathogen to produce soluble toxins or endotoxins
-affect's pathogens virulence
153
bacterial disease
caused by bacteria ( can be gram + or -)
toxins can be exo or endotoxins
154
exotoxin
enzymes the damage plasma membranes of host cells or can inactive enzymes involved with protein synthesis
155
endotoxins
component of gram negative bacteria walls
released in blood
activate the inflammatory response and produce fever
156
bacteremia vs. septicemia
-presence of bacteria in blood
-growth of bacteria in blood
for both
-endotoxins are released in the blood, activating complement and clotting system (increase cap. permeability >hypotension)
157
viral disease
most common
replication depends on ability to infect host
transmission> aerosol, infected blood, sexual contact, vector (things moving ie. mosquito)
158
viral replication
1. phage attaches to host's surface
2. viral DNA enters host cell
3. phage DNA is replicated and phage proteins are made
4.new phage are assembled
5.cell lyses, releases new phages
159
cytopathic effects of viruses
-inhibits host DNA or protein synthesis
-turns host to cancer cell
-disruption of lysosomal membrane release enzyme that damage host
alters antigenic properties of host cell leading to immune system to attack it's own cells
160
influenza and antigenic variation
antigens responsible for protection against influenza change
antigenic shift- major changes of influenza
antigenic drift- small changes in the genes of influenza viruses
antigenic drift allows virus to spread quickly and makes it easy to spread globally
161
fungal infection
large microorganisms with thick cell walls
resist to penicillin
adapt to host's environment
suppresses the immune defence
162
mycoses
diseases caused by fungi
163
dermatophytes
fungi that invades skin hair and nails
i.e ringworm/tineas
164
parasitic infection
symbiotic
unicellular protozoa
tissue damage is secondary to infestation itself with toxin damage
165
environmental countermeasures
waste disposal, water treatment, food safety, vector control
166
antimicrobials
either bactericidal or bacteriostatic
-inhibit synthesis of cell wall and protein synthesis
-damage cytoplasmic membrane
167
bactericidal
drug that kills bacteria
168
bacteriostatic
drug that inhibits the grow and replication
169
vaccines
introduce weakened -attenuated/live vaccines or dead-killed vaccines pathogens to gain antibodies
ex. give protein from virus to make memory cell
170
immune deficiencies
immune system failed
clinical presentations
-develop unusual severe infections
t-cell deficiencies
b-cell and phagocyte deficiencies
complement deficiencies
171
primary immunodeficiency
also called congenital
-genetic anomalies/
-generally not inherited
most result from single gene defect
172
secondary immunodeficiency
also called acquired
-caused by another illness, more common
173
combined deficiencies
result from underdevelopment of T and B lymphocytes
ex. severe combined immunodeficiency (SCID), bare lymphocyte syndrome, WIskott-Aldrich syndrome, DiGeorge syndrome
174
SCID
underdeveloped thymus
absent or reduced IgM and IgA levels
175
bare lymphocyte syndrome
adequate B and T-cells by defective cooperation
inability to produce MHC classes I and II
176
Wiskott-Aldrich syndrome
low IgM production with bleeding
177
DiGeorge syndrome
thymic aplasia or hypoplasia
-poor parathyroid development> t-cell deficiency
178
combined deficiencies evalution
complete blood count/CBC >measure lymphocytes
quantitative determination of immunoglobulins> measure immunoglobulins
assay for total complement
179
combined deficiencies treatment
gamma-globulin therapy
stem cell transplantation
transfusion of erythrocytes
bone marrow transplants
mesenchymal stem cell injection
gene therapy
180
hypersensitivity
altered immunological response to antigen that results in damage or disease
anaphylaxis is a immediate hypersensitivity reaction
delayed reactions> allergy, autoimmunity, alloimmunity
181
autoimmunity
disturbance in immunological tolerance of self antigens
182
type I hypersensitivity
IgE mediated
against allergens (environ. antigens)
sensitized: process where IgE binds to Fc receptors on the surface of mast cells
histamine release from mast cell degranulation
- bind to H1 and H2 receptors, and antihistamines (blocks histamine from binding to receptors)
clinical manifestations: allergic rhinits, systemic anaphylaxis
183
type 1 hypersensitivity physiologic process
1. exposure to allergen
2. antigen presenting cell process the allergen and show to B-cells
3. T-helper cell help B-cell turn to plasma cells to make IgE
4.IgE is stored on the surface of mast cells
5.expose to allergen again, so allergen binds to IgE
6.mast cells then degranulate and release substance like histamine
184
Type II hypersensitivity
tissue specific
5 mechanism
1. cell is destroyed by antibodies and complement, protein help breakdown
2. cells destructed through phagocytosis
3. soluble antigen may enter circulation and deposit on tissue > tissues destroyed by complement activation and neutrophil
4.antibody-dependent cell-mediated cytotoxicity (ADCC) attach to target cell, which attracts immune cells to destroy them
5. target cell malfunction
185
Type III hypersensitivity
-immune complex mediated
-antigen-antibody complexes are formed in circulation and deposited in vessel walls or extravascular tissues, then when detected lysosomal enzymes are released to break down the deposits
not organ specific
ex. Raynaud phenomenon, Arthus reaction
186
Type IV hypersensitivity
cell mediated hypersensitivity
doesn't involve antibody
cytotoxic T lymphocytes or lymphokine-producing Th1 and Th17 cells to direct killing
ex. graft rejection, TB test, allergic reactions from poison ivy or metals
187
allergy
most common hypersensitivity (usually type 1)
exogenous (environ) antigens cause typical immunological responses in genetically predisposed individuals
188
anaphylaxis
most rapid and severe immediate hypersensitivity reaction
systemic or cutaneous
189
desensitization to allergen
may reduce the severity of allergic reaction but can lead to anaphylaxis
190
systemic lupus erythematosus (SLE)
autoimmune condition
chronic multisystem inflammatory disease
autoantibodies against:
-nucleic acids
-erythrocytes
-coagulation proteins
-phospholipids
-lymphocytes
-platelets
deposition of circulating immune complexes containing antibody against host DNA
191
Alloimmunity
immune reaction to tissue of another individual
-bc of ABO and Rh blood groups
Rh: antigens only expressed on RBC
Rh-+ or -
-can lead to hemolytic disease of newborns (other's immune system attacks baby's RBC)
192
O vs AB blood type
O- no antigens > uni donor
AB- both antigens > uni recipient
193
granulocytes
WBC with secretory granules in its cytoplasm,
innate immunity
ex. mast cells, neutrophil, basophil and eosinophil
194
cells [] extra vs. intracellular
extra- high hc03, na, cl
intra- K, P
195
interstitial fluid
fluid that surrounds cells and lymph
196
roles of fluid in the body
temp regulation, transportation, lubrication, chem. reactions, hydration, shock absorption
197
osmolality
[] of solutes in solution
198
osmotic forces
pressure exerted by solutes in solution to draw water across a semi-permeable membrane
199
starling forces
balance of hydrostatic and oncotic P
200
hydrostatic pressure
force against BV walls, pushing water out cap.
higher than osmotic pressure at arterial end of cap.
201
oncotic pressure
pull exerted by protein in plasma drawing water in cap.
higher than hydrostatic pressure at venous end of cap.
202
net filtration pressure
cap. hydrostatic P + interstitial oncotic P (fav. filtration)
-
plasma oncotic P + interstitial hydrostatic P (fav reabsorption)
203
aging effect on total fluid
less as you age
less thirst sensation, kidney function
204
edema
too much fluid in interstitial space
205
third spacing
too much fluid in transcellular space
206
ascites
fluid accumulation in peritoneal cavity
207
pleural vs. pericardia effusion
fluid accumulation in pleural vs. pericardial cavity
208
isotonic, hypertonic, hypotonic fluid volume deficit
isotonic> aka hypovolemia, =h2o and Na loss
ex. hemorrhage,
hypertonic> h2o>Na loss
ex, early kidney disease > cellular dehydration
hypotonic> Na>h2o loss
cell swells
209
isotonic, hypertonic, hypotonic fluid volume
isotonic> aka hypovolemia, =h2o and Na gain
-only extracellular parts expanded
ex. kidney disease
hypertonic> h2o>Na gain
-fluid move from intracellular to intravascular compartment > cellular dehydration
ex, excess Na intake
hypotonic> Na>h2o gain
0fluid move from intravascular to intracellular compartment
cell swells
210
what fluids to to give for isotonic fluid losses
isotonic IV fluids
-0.8% normal saline NS
-Ringer lactate (contain K, don't give if client has high K)
211
what fluids to to give for hypertonic fluid losses
hypotonic IV fluids
5% NS
D5W with 1/2 NS
D5W with RL
-HIGH [] OF Na THAN INSIDE CELL
-pulls fluid out of cells into intravascular space
212
what fluids to to give for hypotonic fluid losses
hypertonic IV fluids
1/2 NS (0.45% NaCl)
1/3 NS (0.33% NaCl)
D4W (5% dextrose in water) (contains glucose)
-lower [] of Na than inside the cells to push fluid into cells from intravascular space
-can cause hypovolemia
213
hypovolemia vs. hypervolemia
too much or little fluid in intravascular space (low blood plasma)
214
hyper vs. hypokalemia
too much or little K in intravascular space
215
hyper vs. hyponatremia
too much or little Na in intravascular space
216
potassium
3.5-5 mmol/l
hyper greater or = to 5 mmol/l
hypo lesser or = to 3.5 mmol/l
maintains heart and muscle contraction
217
K and cardiac AP
phase 0: Na and Ca going in the cell
phase 1: Na channels close
Phase 2: K leaves cell, balance between K and Ca influx
phase 3: Ca channel close
phase 4: K channels close
218
Na
135-145 mmol/l
hyper 145 or high
hypo 135 or lower
controls body fluid distribution > blood volume > BP
219
Cl
moves with Na
involves pH balance
Cl moves from plasma into RBC and HCO3 move into plasma
220
Mg
intracellular cation
involved in neuromuscular contractility
221
hypomagnesemia
causes: insufficient intake (malnutrition, Crohn's), excess excretion
symptoms: tachycardia, HTN, muscle twitching, paraesthesia, hyperreflexia, confusion,
222
hypermagnesemia
increase intake (too much IV, laxatives), decrease excretion
223
Ca
usually low with Mg
absorption depends on vit D (calcitriol)
stored in bones, regulated by PTH and calcitonin
involved in neuromuscular contractility, coagulation and bone health
224
hypercalcemia
greater than 2.60 mmol/l
225
etiology of hypercalcemia
increase absorption, decrease excretion (kidney disease), increase bone resorption (osteoclast breakdown releasing Ca)
226
hypercalcemia structural changes
bone demineralization, osteoporosis (OP), fracture risk
nephrolithiasis (kidney stones)
nephrocalcinosis (calcification of kidneys)
227
hypercalcemia clinical significance
early: polyuria, polydipsia, anorexia, nausea, constipation and fatigue
acute: hypoactive bowel sounds, musculoskeletal weakness
severe: confusion, delirium, com, psychosis
228
hypocalcemia + etiology
less than 2.21 mmol/l
absorption issues, low Mg, excess excretion
229
structural change of hypocalcemia
neuromuscular excitability
osteomalacia (stiff bones)
impaired teeth mineralization
230
clinical significance of hypocalcemia
tetany (involuntary muscle contractions), muscle cramps, paresthesias, Chvostek's (contraction of facial muscle when tapping facial nerve) and Trousseau's (carpal spasm from inflating BP cuff)
arrhythmias
231
P
hyperphosphatemia looks like hypocalcemia
hypophosphatemia looks like hypercalcemia
stored in bones and soft tissues
regulated by PTH and vit. D
bone and teeth health, muscle and RBC function
232
respiratory + metabolic acidosis + alkalosis
-too much co2 > acidic
-too little co2 > basic
233
body's pH
-normal 7.35-7.45
great or = 7.45 > alkalosis
less or = 7.35 acidosis
234
extracellular buffer system
1st line of defence that responds to pH changes
major effects
bicarbonate-carbonic acid
20 hc03 : 1 h2co3
minor
hemoglobin (chloride shift)
- low o2 > cl move in RBC and hco3 moves out (vis versa)
plasma proteins (bind to H when blood's acidic)
phosphates bind to H and excrete it
235
lung's role in pH balance
2nd line of defense
low RR > high co2 > acidosis
high RR >low co2 > alkalosis
236
kidney's role in pH balance
acidosis > a lot of H is secreted and combines with buffers in tubules to be excreted
alkalosis > a lot of hco3 is secrete and combines with Na in tubules to be excreted > can lead to hyponatremia
237
pH and K's relationship
high H move inside the cell to balance pH > K moves outside cells to balance electric force >hyperkalemia
low H in cells > move outside cell to balance pH > k move inside balance to balance electric forces > hypokalemia
238
respiratory acidosis etiology + pathogenesis
high co2 > low pH
-poor exhalation, airway obstruction
239
respiratory acidosis clinical significance + alterations
-hypoventilation, slow RR, low BP, dysthymia, lethargy, confusion, dizziness
-to compensate kidney increase hco3 reabsorption
-chronic > lung fibrosis and hyper inflation
240
respiratory alkalosis etiology + pathogenesis
overventilation of lungs
low co2 > high pH
241
respiratory acidosis clinical significance + alterations
hyperventilation, low BP, dysrhythmias, confusion, dizziness, muscle cramps
acute: none
chronic> electrolyte imbalances
242
metabolic acidosis etiology
-loss too much base ( diarrhea) or retention of too much acid (renal failure)
243
metabolic alkalosis etiology
loss to much acid (vomiting, excessive NG suctioning, retain too much base (excessive hco3 intake
244
metabolic acidosis structural alteration + clinical significance
compensation > hyperventilation
chronic: bone demineralization and muscle wasting
-increase RR and depth, confusion, lethargy, CV collapse, electrolyte imbalances
245
metabolic alkalosis structural alteration + clinical significance
compensation > hypoventilation, hypokalemia and hypochloremia
low RR and depth, irritability, lethargy, confusion, hand tremors, muscle twitching
246
Hematocrit
how much of your blood consists of red blood cells
RBC % in proportion to plasma volume
247
hematopocietic stem cells
HSC
located in bone marrow
gives rise to all blood cells
self renewing through asymmetric division > 1 daughter cell remains a stem cell
248
myeloid progenitors
gives rise to cells that transport oxygen, aid in immune responses and blood clotting
249
lymphoid progenitors
produce lymphocytes (b, t and natural killer cells)
mature in primary and secondary lymphoid organs
-adaptive immune responses
250
myeloid cells
granulocytes
megakaryocytes (produce platelets)
monocytes and macrophages
251
cellular differentiation of blood cells
hematopocietic stem cells (pluripotent can become any cell)
multipotent progenitor cell (MPP)
eosinophiloblast (driven by cytokines and transcription factors IL-5 and GATA- 1
immature eosinophil (producing granule with peroxidase and eosinophil cationic protein
mature eosinophil
252
control of differentiation of blood cells
cytokine and growth factors regulate HSC
colony-stimulating factors (CSF) stim. progenitors of progenitor cells
hematopoiesis pools
peripheral circulation pools
253
hematopoiesis pools
stem cell pool for pluripotent stem cells, bone marrow pool is store for active proliferating cells and mature cells
254
peripheral circulation pools
circulating pool > cells moving through bloodstream
marginating storage pool > consist of neutrophils
255
red vs. yellow bone marrow
active
produces blood cells
ex. vertebrae, cranium, sternum, ribs
-inactive contains fat
256
bone marrow niches
osteoblastic niche > quiescent/ don't divide HSC
vascular niche > proliferation and differentiation of HSC
CAR and nestin-expressing cells
257
medullary hematopoiesis
blood cell production in bone marrow of adults
in fetus its in live and spleen
258
medullary hematopoiesis
suppression of blood cell production
aplastic anemia, leukemia, chemo or radiation damage
259
extramedullary hematopoiesis
production of blood cells outside the bone marrow in adults
in liver, spleen and lymph nodes
260
primary vs. secondary lymphatic organs
thymus and bone marrow
spleen, lymph nodes, tonsils and Peyer patches
261
spleen
fetal hematopoiesis
filters blood, removing damaged or old blood cells
initiates immune responses to bloodborne pathogens
reservoir for blood
has white (lymphocytes) and red pulp (macrophages)
262
filtering lymph
collect interstitial fluid from tissues then goes to the thoracic duct then superior vena cava
263
immune response in lymph nodes
antigens encounter lymphocytes
> B and t cells enter lymph nodes from blood
processed by macrophages and dendritic cells
B cells proliferate and differentiate into plasma and memory cells
macrophages filter lymph of debris and foreign substances
264
erythropoiesis
megakaryocyte erythroid progenitor > proerythroblast >erythroblast>reticulocyte >RBC
265
erythropoietin
EPO
tissue hypoxia> increase EPO > increase RBC
low EPO > anemias, CKD
high EPO> COPD
266
hemoglobin molecule
globin chains > 2 alpha and two beta polypeptide chains
heme groups > iron and protoporphyrin
267
hemoglobin synthesis
protoporphyrin and iron (reduced = 2+) combine
carries four o2
oxyhemoglobin >bound to o2
268
role of vitamin b 12
require to form thymidine during DNA replication
low b12 > impairs DNA synthesis > abnormal RBC production ?megaloblastic anemia
low intrinsic factor > poor b12 absorption> pernicious anemia
269
role of iron in erythropoiesis
required to form hem in Hgb
stored in liver as ferritin
low iron ? impaired hgb synthesis > abnormal RBC production > iron-deficiency anemia
270
iron transport and recycling transferrin
transferrin binds to iron using transferrin receptors in blood
cells release apotransferrin back in the bloodstream
in mitochondria of erythroblasts heme synthetase insert iron into protoporphyrin
271
hepcidin
high iron levels or inflammation increase the production of hepcidin
low iron stores or increase erythropoiesis decrease production
-binds to ferroportin > ferroportin degradation > decrease iron release in bloodstream
272
iron absorption
iron stores are low > increase absorption transported into plasm
sufficient amount > decrease absorption and excess iron is stored as ferritin
273
normal RBC destruction
110-120 days
decrease ATP > more fragile RBC > rupture
274
bilirubin
Hgb broken down > bilirubin
conjugated bilirubin > excreted in bile > bacteria converts it into urobilinogen > excreted
275
plasma
50-55% of blood volume
proteins like albumin (maintains oncotic pressure), globulins (antibodies), fibrinogen (clotting)
electrolytes
276
erythrocytosis
high RBC
ex. chronic lung diseases and polycythemias
277
high hematocrit
true increase > increase RBC > polycythemias
vascular fluid volume deficit (dehydration but normal amount of RBC)
278
low hematocrit
true decrease > low RBC > renal failure, low EPO
vascular fluid volume excess > overhydration (normal RBC but more plasma)
279
polycythemia
elevated RBC
mutated JAK2 gene causing uncontrolled blood cell product
increase blood viscosity, hyperactive bone marrow
fatigue, headache, puritis, thrombosis and splenomegaly (enlarged spleen)
280
pernicious anemia
macrocytic-normochromic anemia
low b12, low intrinsic factor
DNA synthesis RBC is disrupted > macrocytic erythrocytes (abnormal, large erythrocytes)
weakness, fatigue, abdominal pain, smooth sore tongue
low rbc, hgb, hct, increase MCV
281
iron deficiency anemia
microcytic-hypochromic anemia
chronic blood loss, low intake
stage 1: depletion of iron store
stage 2: low iron supply to bone marrow
stage 3: iron deficient rbc enter circulation
microcytic/small hypochromic (pale) erythrocytes
fatigue, weakness, pale skin
low hgb, hct, MCV, MCH, MCHC
low ferritin
282
beta thalassemia major and minor
microcytic-hypochromic anemia
genetic mutation in HBB gene
autosomal recessive
excess alpha globin chain in rbc > ineffective erythropoiesis
microcytic/small hypochromic (pale) erythrocytes
low mature rbc
extramedullary hematopoiesis
minor > mild anemia
major > sever, transfusion dependent anemia
283
sickle cell anemia
normocytic-normochromic anemia
autosomal recessive
mutation in HBB gene > hemoglobin S
low o2 > sickle shaped rbc> vaso-occlusion and hemolysis
none marrow hyperplasia
chronic anemia, vaso-occlusive crisis, infection risk
284
aplastic anemia
normocytic-normochromic anemia
bone marrows fail to produce enough blood cells
caused by chemo, radiation
bone marrow damage and stem cell destruction
hypocellular bone marrow
pancytopenia low rbc, wbc plts
severe anemia, infection risk ,bleeding issues
285
leukocytosis
high wbc
infection, stress, autoimmune, meds (steroids), allergic reactions,
286
leukopenia
low wbc
lymphomas, AIDSs, meds (chemo)
287
wbc differential
percentage/proportion of different wbc types
288
neutrophilia
increase neutrophils
bacterial infections, stress necrosis, leukemias
bands > immature neutrophils
polymorphonuclear leukocytes
289
neutropenia
decrease neutrophils
severe bacterial sepsis, drugs causing bone marrow depression (chemo)
290
lymphocytosis
increase lymphocytes
viral and chronic bacterial infections
291
lymphopenia
decreased lymphocytes
AIDs, meds, cytotoxic meds
292
eosinophilia
increased eosinophils
antigen-antibody reactions, parasitic infections
293
monocytosis
increased monocytes
chronic inflammatory infections, inflammatory conditions
294
leukemia
cancer that originate in bone marrow
acute> fast growing blats
chronic> slow and mature wbc
lymphocytic> lymphoid progenitor cells
myelocytic > myeloid progenitor cells
295
acute lymphocytic leukemia
caused by genetic and environmental factor
common in children
immature lymphoblasts in bone marrow become cancerous> can't differentiate
philadelphia chromosome and translocation of T 12 + 21
anemia, thrombocytopenia, neutropenia, fever, bone pair, swollen lymph nodes
296
chronic myeloid leukemia
philadelphia chromosome
297
philadelphia chromosome
translocation of chromosome 9 and 22 > permanently active tyrosine kinase causing uncontrolled cell proliferation
malignant myeloid stems cells causing excess mature and immature granulocytes
chronic phase> asymptomatic or mild symptoms
accelerate phase > treatment resistant
blast crisis > CML transforms into an aggressive acute leukemia > bone marrow failure
298
lymphomas
cancer from lymphocytes
develop in lymphatic system
Hodgkin's and non-Hodgkin's lymphoma
299
Hodgkin's lymphoma
reed-sternberg cells >large abnorm. lymphocytes
starts in a single lymph nodes or chain of nodes
300
Non-Hodgkin's lymphoma
don't involev reed-sternberg cells
arises from b or t cells
genetic, immunodeficiency, environment, chronic infections
lymph node enlargement, extranodal involvement, modular patterns (diffuse, nodular)
painless lymphadenopathy, fever,
symptom can be aggressive or indolent
301
thrombopoiesis
myeloid stem cells become megakaryocyte
endomitosis of megakaryoblasts > large polyploid megakaryocytes
megakaryocytes fragment into platelets
thrombopoietin regulates platelets productions
302
hemostasis
1.vascular injury and vasoconstriction (decrease blood flow to decrease blood loss)
2. primary hemostasis
-adhesion, activation, secretion, aggregation
3. secondary hemostasis
4. clot contraction (stabilizes clot)
5. fibrinolysis and healing
303
primary hemostasis
von Willebrand factor binds with collagen on platelets so they adhere to the injury site
platelets become spikey shape and release ADP and thromboxane A2 for platelet activation
-releases serotonin and calcium to cause vasoconstriction
platelet aggregation (binds to fibrinogen)
304
nitric oxide and prostacyclin
inhibits platelet aggregation and vasoconstriction
produced by endothelial cells
prevents unnecessary clotting
305
von Willebrand factor
facilitates platelet adhesion to exposed subendothelial collagen
stabilizes factor 8 in circulation
306
thromboxane A2
platelet activator and vasoconstrictor
produced from arachidonic acid
307
fibrinogen
bridges activated platelets together via GP2B/3A receptors
facilitates aggregation
308
secondary hemostasis
activation of clotting factors
-makes fibrin clot
intrinsic pathway: needs Ca and VWF
starts collagen activates factor 12
end 10 to 10a
extrinsic pathway: needs Ca
starts tissue damage, >tissue factor > factor 7
end 10 to 10a
common pathway needs Ca
start 10 to 10a
prothrombin > thrombin
ends fibrinogen > fibrin
309
thrombocytosis
high platelet count
clotting risk
ex. malignant neoplasm
paradoxical hypercoagulation > bleeding bc abnormal platelets
310
thrombocytopenia
low platelet count
hypercoagulation > bleeding risk
ex, autoimmune conditions, bone marrow suppression
311
prothrombin time (PT)
test of extrinsic pathway
in sec
international normalized ratio (INR)
-test that standardizes PT
-monitored closely for clients taking Warfarin
high PT - bleeding risk
low PT - clotting risk
312
partial thromboplastin time (PTT)
test of intrinsic pathway
in sec
monitored closely for clients taking Heparin
high PTT= bleeding risk
low PTT= clotting risk
313
factor V Leiden
mutation of f5 gene encodes factor v
autosomal dominant
314
other
flashcards
Decks in class (16)
# Cards
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112094
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1180250
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N2250104
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N227097
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216349
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Pathophysiology314
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Pathophysiology- week 262
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Pathophysiology- week 323
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Pathophysiology- week 436
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Pathophysiology- week 5 + 611
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Pathophysiology- week 743
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Pathophysiology- week 851
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Pathophysiology- week 923
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Pathophysiology- week 1020
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Pathophysiology- week 1140
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Pathophysiology- week 1243
