Exam #2 Flashcards
(391 cards)
1
Q
Age-Related vs. Age-Induced
A
each age set has different diseases associated with it
2
Q
Age-Related:
Over 65 Years
A
heart disease 38.5% cancer 19.6% stroke 10.4% chronic respiratory disease 7.9% Alzheimer's disease 0.6%
3
Q
Cognitive Dysfunction
A
diseases related to aging in the central nervous system
4
Q
Senscence Genes
A
not entirely proven
responsible for aging
5
Q
Cellular Senescence
A
diploid cells lose ability to divide
6
Q
Replicative Senescence:
Hayflick Limit
A
- some cells become senscent after a certian number of cycles
- telomeres shorten in response to DNA damage and replication
7
Q
Apoptosis
A
self-destruction of cells if genetic lesions is profound and irreparable
8
Q
Mutation Accumulation Theory
A
life today doesn’t give in to natural selection the way it happens in the wild, without selection of the diseased and such mutations accumulate causing new and different diseases then what would happen in nature
9
Q
Antagonistic Pleiotrophy Theory
A
the idea that some genes have a beneficial effect early in life become damaging later in life when its usefulness is over
10
Q
Disposable Soma Theory
A
the idea that the body allocates energy to more important functions
11
Q
Telomere Shortening
A
at each end of chromosomes
prevent fusion into rings or binding to each other
shorten each time the cell divides
when it becomes too short the DNA gets damaged and the cell dies
12
Q
Intrinsic Factor
A
telomere shortening
13
Q
Extrinsic Factor
A
free radical damage
14
Q
Free Radical Damage
A
peroxides and singlet oxygen made in cells
generate free radicals
capable of damaging structural proteins and DNA
15
Q
Progeria
A
accelerated aging disease in children
protein lamin A
die from atherosclerosis, such as heart attack or stroke
16
Q
Nuclear Sclerosis
A
compression of lens fibers in central lens
results in haze in old dogs eyes
17
Q
Presbyopia
A
lens lose some elasticity
compound by reduced contractility of the smooth muscle controlling lens shape
18
Q
Retinal Atrophy
A
periphery of the retina
splitting of sensory retina due to the development of small cysts
19
Q
Microcystoid Degeneration
A
splitting of sensory retina due to development of small cysts due to retinal dystrophy
20
Q
Vitreal Liquefaction
A
normal vitreous filled with gelatinous material
between lens and retina
happens with age
results in retinal detachment
21
Q
Rhematogenous Detachment
A
disease name for the process of complete retinal detachment
22
Q
Asteroid Hyalosis
A
vitreal change
accumulation of small mineralized bodies composed of calcium, sulfur, and phosphorous in vitreal gel
23
Q
Glaucoma
A
intraocular pressure rise
due to senescent deletrious changes in drainage angle between iris and cornea
also known as intraocular pressure
24
Q
Hyaline Degeneration
A
affects ciliary body and associated vessels
results in accumulation of of amorphous material
arcus senilus of corneoscleral junction
25
Arcus Senilus
affects corneoscleral junction
due to lipid accumulation in the cornea
results in opaque arc or ring at the edge of the cornea
26
Drusen
acellular structures
accumulates behind non-sensory part of the retina
central retinal degeneration
27
Age-Related Macular Degeneration (MD)
in people
when too many large drusen formations in macula
associated with mutations in several proteins inhibiting the complement cascade
28
Complement System
part of the innate immune system
| complements the activity of antibodies and white blood cells in eliminating pathogens
29
Benign Hyperplasia Nodules of the Liver
not preneoplastic
| confuse vets in exploratory abdominal operations
30
Splenic Hyperplastic Nodules
common in the aging spleen due to proliferation of large aggregates of lymphocytes, some appear atypical
31
Siderotic Nodules
splenic deposition of iron plaques on elastin in the capsule
| look more innocent than they are
32
Prostatic Hyperplasia
difficult urination and constipation
| affected glands 4x their normal size
33
Pancreatic Hyperplasia
affects the exocrine pancreas
| small flat white plaques on the surface of the gland
34
Osseous Metaplasia
form in the meninges
| fibrosis and plaques of bone
35
Ventricular Enlargements
occurs in brain of 10+ year old dogs
toward front of brain
associated with reduced brain volume
36
Atrophy of the Frontal and Prefrontal Cortex
reduced cognitive function with deposition of one form of amyloid in extracellular plaques
37
Amyloid Deposits
brains of dogs
amount of amyloid peptide deposition varies
toxic to neurons
responsible for cell loss and atrophy in cerebral cortex and hippocampus
38
Neurofibrillary Tangles
occur in the cytoplasm of neurons
typical of AD
not seen in dogs with cognitive dysfunction
39
Forms of Cell Death
necrosis, apoptosis, autophagy, autolysis
40
Necrosis
'becoming dead'
| lethal degeneration of cells, tissues, organs
41
Apoptosis
'separation falling'
under cellular control
'programmed cell death'
42
Autophagy
'self eat'
survival mechanism of cells
usually nutritionally related, starvation
when it can no longer cannibalize effect or duplicate organelles and other inracellular components
43
Autolysis
'destruction'
post-mortem phenomenon
result of cellular disintegration induced by release of lysosomal enzymes into the cytoplasm and activities of post-mortem
quick lysis in intestines, pancreas, gallbladder, liver, kidney, retina
slow lysis in skin, bone, tendons
intermediate lysis in muscle, lungs
rate dependent on temperature and oxygen
44
Coagulative Necrosis
infract
process of cell death when arterial blood supply is abruptly lost
exp. heart attacks/strokes
denaturation of intracytoplastic protein
dead tissue that's infracted will turn to connective scar tissue
45
Liquefactive Necrosis
dead tissue liquefies
in central nervous system (brain/spinal cord)
most evident where little connective tissue stroma
exp. abscess/boil
pus bacteria cause one class of white blood cells (neutrophils)
46
Caseous Necrosis
'cheese-like'
caseating lesion, particularly in lymph nodes and lungs
TB?
due to presence of abundant lipid, coagulated protein.
often contain calcium
47
Fat Necrosis
'steatonecrosis'
when adipose tissue dies
may occur after trauma to mammary tissue
white and dry
48
Gangrene
'gnaw'
tissue necrosis occurs with with concurrent infection
two forms
49
Gangrene:
| Gas
gas-forming bacteria
tissues crepitant due to carbon dioxide due to sugar fermentation
occurs in severe frost bite, ischemia, deep penetrating injuries, appendicitis
50
Gangrene:
| Dry
gradual narrowing of blood vessels
frostbite in calves
some intoxications
51
Features of Necrosis
it has distinctive morphological features
energy independent
no protein synthesis occurs
triggers inflammation
52
Necrosis:
| Mechanism
a fundamental concept is that the formation of free radicals is a final common pathway leading to cellular death
53
White Muscle Disease
'nutritional myopathy'
calves, lambs, foals
muscular disease due to selenium deficiency
low vitamin E and low selenium
54
Free Radical Mechanisms
```
spontaneous decay
superoxide dismutase
catalase
glutathione peroxidase
vitamin E
```
55
Free Radical Creation
```
radiation
intoxication
aging
oxygen toxicity
inflammation
```
56
Features of Apoptosis
```
morphologically distinct
energy dependent
requires protein synthesis
does not trigger inflammation
induced by extrinsic and intrinsic pathways
```
57
Liable Cells
constantly cycling, regenerate rapidly
58
Stable Cells
quiescent or slow cycling cells
| maintain a capacity for cell division/regeneration
59
Permanent Cells
do not cycle
| there is no meaningful capacity for regeneration
60
Crypts of Lieberkuhn
surrounded by reserve/basal cells of the epidermis
| in small intestine
61
Totipotential Stem Cells
from embryo
| potential to differentiate along virtually any cell line
62
Pleuripotential Stem Cells
differentiate along multiple, but not all, cell lines
63
Atrophy
decrease in the size of cells, tissues, organs as a whole
| can be due to decrease of size in individual cells or decrease in number of cells
64
Involution
synonymous with atrophy
refers to normal physiological reduction in size of tissues or organs such as the pregnant uterus after parturition or decrease in size of thymus that occurs early in life
65
Atrophy:
| Decreased Use
exp. skeletal muscle mass when limb is immobilized following a fracture
both types affected but 2 more severely
66
Atrophy:
| Decreased or Faulty Nutrition
'serous atrophy of fat'
body fat stores during dieting/starvation
white/tan fat stores converted to translucent, gelatinous tissue substance
results in atrophy of liver
67
Atrophy:
| Inadequate Blood Flow
sudden abrupt/complete cessation of blood flow
causes necrosis to affected tissue (infraction)
exp. blood clots (thrombi or emboli) occluding blood vessels in the brain/heart causing stroke/heart attack
limiting oxygen and nutrients
68
Thrombi/Emboli
blood clot due to blood coagulation
| intravascular mass capable of lodging
69
Atrophy:
| Increased Local Pressure
space occupying lesion increasing pressure in surrounding tissues resulting in atrophy
70
Hydronephrosis/Hydrocephalus
one kidney swells due to back up of urine
| fluid in skull due to brain swelling
71
Atrophy:
| Hormones
chemicals produced in one part of the body
| atrophy due to deficiency of a hormone
72
Ovariectomy
result in marked artophy of target tissues such as uterus and mammary gland
73
Atrophy of Thyroid Gland
thyroid gland/secretion of thyroid hormone are regulated by thyroid stimulating hormone (TSH) produced by secretory neurons in the hypothalamus
if this area of hypothalamus is destroyed, TSH is no longer produced and thyroid glands atrophy
74
Atrophy:
| Old Age
many tissues suffer some degree of atrophy during aging process
total body mass decreases
decrease in weight of some organs (brain, liver, kidney, spleen)
75
Atrophy:
| Denervation
most applicable to skeletal muscle
| when nerves to skeletal muscles are damaged, muscle becomes small and atrophic
76
Atrophy:
| Immune Mechanisms
body develops antibodies against its own tissues
| exp. pernicious anemia
77
Pernicious Anemia
autoantibodies are produced against parietal cells of the gastric lining (mucosa) resulting in a loss of these cells and atrophy of the mucosa
also produce intrinsic factor
78
Pathogenesis of Anemia
1) intrinsic factor, required for the absorption of vitamin B12 from the small intestine is deficient
2) vitamin B12 is a cofactor for enzymes required for normal production of red blood cells
79
Hashimoto's Thyroiditis
swelling of the thyroid gland resulting in reduced function
| example of atrophy due to autoantibodies
80
Atherosclerosis
atrophy in thyroid gland leads to disturbances in the skin and fat metabolism
leads to hardening in the arteries
81
Hepatic Encephalopathy
when liver atrophy is caused by a portavacal shunt
encephalopathy is not due to atrophy due to the vascular anomaly shunts blood around the liver
the functional capacity for eliminating potential toxins from the blood such as ammonia remains but can't be used
82
Hypertrophy
increase in the size of an organ or tissue due to an increase the SIZE of individual size
exp. right-sided cardiac hypertorophy
83
Hyperplasia
increase in the size of an organ or tissue due to an increase in the NUMBER of cells
exp. congenital hyperplastic
84
Dystocia
from congenital hyperplastic goiter in small ruminants from sufficiently large thyroid glands
85
Thyroid Glands
consists of follicles lined by cuboidal or coumnar epithelial cells
dense pink-staining amorphous proteinaceous fluid content of the follicles is call colloid
86
Brisket Disease:
| 'Cor Pulmonale'
'high altitude disease'
enlargement of skeletal muscles as pathological response
low oxygen tension at high altitudes results in reflex constriction of pulmonary arteries that increase intravascular pressures and work load on right ventricle enlarging it
87
Cushing's Disease
'hyperadrenocorticism'
tumor of pituitary gland secretes excess ACTH
stimulates adrenal cortex to produce excess cortisol
88
ACTH
adrinocorticotropic hormone
89
Acromegaly
excess production of growth hormone resulting in increasing size of tissues over time
90
Erythropoietin
controls red cell production
produced in excess during anemia
bone marrow produces erythoropoietin
91
Excess Nutrition
obesity
| dramatic increase in protein synthesis throughout the body
92
Increased Blood Flow
vascular tumors
fractures
osteomyelitis
-can increase length of limb due to increased blood flow
93
Mechanical Factors
skin callus at point of mechanical stress
94
Osteomyelitis
bone infection caused by bacteria
95
Metaplasia
```
conversion of cells in a tissue or organ from one type to another
usually of the same class
in most cases connective tissue metaplasia insignificant
epithelial metaplasias highly significant
```
96
Metaplasia:
| Chronic Irritation
following permanent tracheostomy
conversion of normal stratified columnar epithelium to stratified squamous epithelium in skin/oral cavities
osteum (opening) not warm or moistened but turbid causing irritation
97
Florid Fibroplasia
connective tissue metaplasia
areas of repair
neoplasms with a proliferative connective tissue component
formation of fibrous tissue
98
Osseous Metaplasia
change of fibrous tissue from fibroplasia into bone
99
Nutritional Deficiency
Vitamin A
required for integrity of many sensitive epithelial tissues
results in the conversion of olumnar epithelial to stratified squamous epithelium in many tissues
exp. submucosal glands of the esophagus in avian species
100
Lacrimal Gland
gland above eyes that secretes tear film
| can be affected by Vitamin A deficiency
101
Hormone Excess Neoplasm
Sertoli cell tumor
- in testes of dogs, secretes estrogen
- conversion of prostatic epithelial cells to stratified squamous epithelium
102
Metaplasia:
| Examples
- squamous metaplasia of submucosal glands in the esophagus can result in blockages and accumulation of keratinaceous debris in the duct lumens
- squamous metaplasia of the urinary system in birds leads to partial obstruction, retention of urates, and gout
- squamous metaplasia in the epithelium lining the trachea and bronchi deaden function predisposing to respiratory disease
103
Gout
arthritis
| acid builds up in blood causing inflammation of joints
104
Dysplasia
disordered development or adaptation
| refers to a proliferative response where there is disorderly replication and maturation of cells
105
Dysplasia:
| Causes
cellular injury over time
| constant low-grade injury that damages but doesn't kill the cells
106
Preneoplastic
leads to development of cancer/tumors
| also dysplasia
107
Melanoma
repeated life-long exposure to solar radiation
malignancy
(also basal and squamous cell carcinomas)
most dangerous skin cancer
leading cause of death in skin cancers
108
Squamous Cell Carcinomas
nonmelenoma cancer
| due to repeated exposure to UV radiation
109
Squamous Cell Carcinomas of Animals
- in conjunctiva and cornea of horses/cattle particularly those with little melanin pigment
- of nasal planum and tips of ears in white cats
- 'hemangioma/hemangiosarcoma' in sparsely haired lightly pigmented abdominal skin in some dogs
110
Hamangioma/Hemangiosarcoma
- abnormal build of blood vessels
| - very quickly growing invasive cancer, affects spleen and heart
111
Hyperplasia
wanes once inductive stimulus removed
112
Oncology
are and science of tumors
113
Neoplasia
'new tissue'
| encompasses benign and malignant masses
114
Cancer
literally means crab
| means malignant neoplasm
115
Tumor/Mass/Growth
clinical swelling
| used as synonyms for neoplasia
116
Benign
```
'-oma'
generally well differentiated and not life threatening
resembles tissue of origin
tends to compress rather than invade
never metastasizes
low rates of mitosis
```
117
Malignant
```
cells tend to be anaplastic
less differentiated
high mitotic rates
tends toward pleomorphism
grows rapidly
```
118
Pleomorphism
cells varying in size and shape
119
Cutaneous Squamous Cell Carcinoma
associated with solar exposure
| rapidly ulcerating mass
120
Metastasis
unequivocal sign of malignancy
| spread from tissue of origin to another location
121
Carcinomas
arise from tissue derived from fetal ectoderm or endoderm
122
Sarcomas
arise from mesenchyme
| -connective tissue, bone, cartilage, muscle
123
Adenocarcinoma
mammary gland tissue tumor
124
Fibrosarecoma
arising from fibrous connective tissue
125
Carcinosarcomas
arise from epithelial and mesenchymal constituents
| common in mammary tumors in dogs
126
Cutaneous Histiocytoma
'button ulcer'
fast growing round cell tumor in young dogs
moderately pleomorphic from an antigen-presenting cell population in skin (dendritic cells)
127
Extramedullary Plasmacytoma
histologically looks malignant
rarely metastasizes
moderately pleomorphic
contains atypically large 'giant' cells
128
Aggressive Tumor in Dogs
histologically low-grade yet biologically high-grade fibrosarcoma of the canine mandible and maxilla
129
Grading and Staging
clinical versus pathological
130
Kaplan-Meier Curves
biological meaning in the form of long-term survival as predicted by histological grade on size and location of tumor and pleomorphism, anaplasia, tissue necrosis, and mitotic rate
131
Anaplasia
loss of differentiation in cells
132
Immunohistochemsitry
characterize the antigenic content of tumors
| detection of estrogen/progesterone for breast cancer detection
133
Molecular Profiling
use of microarray technology
| mRNA extracted from patient's tumor is analyzed to determine which genes are up and down regulated
134
TNM Staging System
```
T= tumor
N= lymph node
M= metastasis
0, I, II, III, IV
based on number 1-4 assigned to TNM
```
135
Stage 0
exp. carcinoma in in situ
136
Stage 1
exp. invaded a little into tissue of origin
137
Stage II
exp. invaded tissue extensively
138
Stage III
exp. spread to local lymph nodes
139
Stage IV
exp. extensive metastasis throughout the body
140
Staging
takes into account size of tumor, depth of penetration, whether it invades adjacent organs, how many lymph nodes have metastases, whether there is spread to distant organs
141
Causes of Cancer
```
neoplastic
trauma/physical
age-related
nutritional
intoxication
infectious
genetic/development
immune-mediated
```
142
Trauma/Physical
burns, solar and x-irradiation, foreign body material
sarcomas at microchip sites
unclear if inflammation is what results in neoplasm or not
143
Age-Related
most cancers occur in second half of life
-accumulation of somatic mutations
-age-related decline in immune competence/surveillance
leukemia in children
144
Secondary Cancer
effects cancer-survivors
| high rate post treatment
145
Infectious
relatively common cause of cancer in young animals
| sequel to Helicobacter pylori
146
Nutritional
high-fat diets
| alcohol
147
Genetic
little information
estimated 10%
BRCA-1 and -2 in breast cancer
148
Immune-Mediated
in immunosuppressed
149
Neoplasm Components
tumor population
supporting fibrous connective tissue matrix
blood supply
inflammation
150
Neoplasm Components:
| Nerves
most lack nerve supply
| pain comes from compression on surrounding tissues
151
Neoplasm Components:
| Inflammation
due to tumor antigens, necrosis, or both
152
Scirrhous or Desmoplastic Reactions
evoke little connective tissue
| induce excessive response
153
DFTD:
| Devil Facial Tumor Disease
```
unusual transmissible tumor
-only other transmissible venereal tumor
spread similar to infectious disease
fatal within 6-9 months
affected by 2
100% fatal within 6 months of appearance
transmitted during fighting/eating
clonal cell line originating in one animal then serially propagated
only 13 chromosomes instead of 14
probably originated from Schwann cells which are responsible for myelin sheath around peripheral nerves
```
154
DFTD:
| Pathogenesis
allografts establish in fresh bitten hosts
evade immune surveillance
develop into large masses that affect breathing, vision and eating
155
Tumor Genes
oncogenes
| tumor suppressors
156
Oncogenes
cause transformation of normal cells into tumor cells
| encode oncoproteins
157
Oncoproteins
proteins responsible for cellular transformation
158
Proto-oncogenes
genes that if mutated or expressed at a high level can become oncogenes
159
Oncogenes:
| Categories
```
growth factors
growth factor receptors
cell cycle regulators
signal transducers
regulatory proteins
('green light' for cell growth)
(lead to gain of function)
```
160
Oncogenic
activate gene expression or gene function
- gene amplification
- gene translocation
- promoter insertion
161
Cyclin B
cell cycle regulator
regulates M phase of mitosis
deregulation leads to cellular transformation
(unregulated proliferation)
162
MYC
transcription factor that regulates transcription of genes that lead to cell proliferation
163
Tumor Suppressors
usually must lose/mutate both copies of gene/allele
loss of function
play critical role in controlling normal cell growth
-many regulate proliferation by governing movement of cell through cell cycle
164
Tumor Suppressors:
| Categories
DNA repair regulators
regulators of apoptosis (cellular suicide)
intracelllular signal transduction regulators
165
p53
'cellular policeman'
not involved in normal cell cycle regulation
increased amount/lifespan of p53 during times of DNA damage
regulates entry into cell cycle
stimulates DNA repair genes
166
p53:
| Inactivation
```
mutations
viral proteins (papilloma viruses)
cellular proteins
-inactivated = loss of function
*greater than 50% of human neoplasms contain a mutation in p53
```
167
Metastasis
spread from site of origin to distant site
primarily via lymphatics (carcinomas) or blood vessels (sarcomas)
tumors originating in the eye or CNS rarely metastasize
no benign tumors metastasize
168
Metastasis:
| Blood (Hematogenous) Pathway
'1st capillary bed theory'
easy for tumor cells to get caught
-liver/lungs common sites for metastatic tumors
more complicated in reality
169
Metastasis:
| Lymphatics
connected to blood circulation
| -not completely separate from hematogenous
170
Metastasis:
| Implantation (Transcoelomic)
tumor breaks through lining of organ, tumor cells are shed ad coat adjacent organs
carcinomatosis
171
Carcinomatosis
seeding of the body cavities with tumor metastases
172
Mechanism for Metastasis
1) cells detach from main tumor mass
2) cells invade BM
- tumor cells actively degrade BM by increased cellular protease activity
3) cells enter/pass the extracellular matrix
- up regulate collagen, fibronectin, ect.
4) cells invade blood vessels/lymphatics
5) travel bloodstream
- form embolus (small clusters)
- emboli may be recognized by immune system
6) extravasate from vessel, invade ECm at metastatic site
7) angiogenesis
8) growth of metastatic tumor
173
Paraneoplastic Effects
```
cachexia
fever
hypoglycemia
hypercalcemia
Sertoli cell tumors
```
174
Paraneoplastic:
| Cachexia
loss of condition (body fat, muscle mass)
diminished immune system
generalized weakness
not simple anorexia/starvation
effects are not proportional to size of tumor
disturbances of metabolism of carbs/proteins/lipids
TNF-a (tumor necrosis factor), IL-1 (interleukin-1), IFN-g (gamma interferon) may be involved
175
Paraneoplastic:
| Fever
can occur without reason
| may be caused by release of cytokine (IL-1 or IL-6) by tumor cells
176
Paraneoplastic:
| Hypoglycemia
low glucose in the serum
can lead to seizure and death
beta cells in the islets of the pancrease produce insulin which decrease blood glucose
some tumors cause hypoglycemia from unknown mechanisms
177
Beta Cell Carcinoma:
| Insulinoma
lead to excess uncontrolled insulin release and lead to hypoglycemia
178
Paraneoplastic:
| Hypercalcemia
increased calcium in serum
excess parathyroid hormone, major regulator of calcium levels in the body
-may produce ectopic parathyroid hormone
occur via direct tumor invasion/destruction of bone
common in lymphoma patients
179
Paraneoplastic:
| Sertoli Cell Tumors
cells of the seminiferous tubules in testes that secrete estrogen/ estrogen-like substances
estrogen usually localized but a large mass releases estrogen causing feminization
-symmetric hair loss, enlarged mammary glands, attractiveness to other male dogs
180
Infectious Cancers
viral and bacterial infections can lead to cancer
181
Human Papillomavirus (HPV)
family of DNA viruses that infect stratified epithelium and mucous membranes
some serotypes cause noncancerous warts
182
HPV:
| Cervical Cancer
HPV-16 and HPV-18 mostly
causes series of cytologic changes that convert squamous epithelium to glandular epithelium
-most clear naturally, chronic become cancer
183
PAP Smear
look for abnormal cells
- most successful cancer screening test
- 80% reduction in cases
- world wide most common cause of cancer death
184
HPV Vaccine
100% effective in prevention of included serotypes
most common serotypes only
prevents precursor change
185
Endogenous
generated within the body, organ, tissue, or cell
186
Exogenous
'foreign' substances from outside the body that gain access to organs, tissues, or cells
187
Nature of Accumulated Intracellular Substances
1) a normal cellular constituent accumulates in excess
2) an abnormal substances accumulates
3) pigments, compound imparting a change in color to cells, tissues, organs
188
Pathogenesis/Significance of Intracellular Accumulations
1) a normal endogenous produced at a normal or increased rate but the rate of metabolism is inadequate
2) an abnormal substance accumulates due to faulty synthesis
3) normal endogenous substances accumulate due to faulty catabolism or degradation
4) an exogenous substance accumulates because it cannot be catabolized
189
Hydropic Change
water insides cells that results in cellular swelling
190
Fatty Change
```
accumulation of lipids in hepatocytes
example of (1)
'hepatic lipidosis', 'hepatic steatosis', 'fatty liver'
```
191
Fatty Change:
| Pathogenesis
inter-related metabolic pathways involving free fatty acids
in the liver FAs are converted to triglycerides
then complexed with apoproteins to form lipoproteins that can be exported from the liver
192
Free Fatty Acids
can be derived from the diet, from chylomicrons in the blood, or from mobilization of fat stores in adipose tissue
193
Anorexia
'starvation'
one of the most common causes of hepatocellular fatty change
mobilization of fat from adipose tissues exceeds the capacity of fatty acid metabolism and fatty acids/triglycerides accumulate in hepatocytes
194
Hypoproteinemia
abnormally low levels of proteins in the blood due to malabsorbtion
195
Ketosis
complex disease of ruminants that results in severe hepatic fatty change
associated with increased energy demands of lactation or twin lambs
fatty liver is due in part to mobilization of fat stores for energy
196
Atherosclerosis
accumulation of lipids in cells
197
Hypothyroidism
...
198
Infraction
...
199
Hyaline Droplet Change
...
200
Proteiuria
...
201
Renal Amyloidosis
...
202
Myoglobin
...
203
Rhabddomyolysis
...
204
Hemoglobin
...
205
Hemolysis
...
206
Russell Bodies
...
207
Mott Cells
...
208
Diabetes Mellitus
...
209
Cushing's Disease
...
210
Cloudy Swelling
...
211
Parkinson's
...
212
Alzheimer's
...
213
Huntington's
...
214
Abnormal Accumulation due to Faulty Synthesis
...
215
Normal Endogenous Accumulation due to Faulty Catabolism/Degradation
...
216
Exogenous Accumulates Because it cannot be Catabolized
...
217
Anthracosis
...
218
Asbestosis
...
219
Silicosis
...
220
Pneumoconiosis
...
221
Mesothelioma
...
222
Plumbism
...
223
Edema
...
224
Hyalin Membranes
...
225
Amyloid
...
226
Amyloidosis
...
227
Immunocyte-Associated Amyloidosis
...
228
Multiple Myeloma
...
229
Osteolytic
...
230
Neoplasms
...
231
Plasmacytomas
...
232
Cachexia
...
233
Acute Phase Proteins
...
234
Familial (localized/systemic) Amyloidosis
...
235
Transthyretin
...
236
Familial Mediterranean Fever
...
237
Amyloid of Aging
...
238
Congophilic Angiopathy
...
239
Senile Plaques
...
240
Neuropile
...
241
Endocrine Amyloidosis
...
242
Prion Diseases
...
243
Proteinuria
...
244
Transmissible Spongiform Encephalopathies
...
245
Long Incubation Periods
...
246
Transmissible
...
247
Brain Lesions
...
248
Mineralization
'calcification' 'ossification'
| process by which certain tissues such as bone and teeth are converted to hard substance
249
Calcium
most abundant cation
mostly stored in bone
involved in numerous cellular processes
excitability of cells in nervous system, contractility of skeletal muscle, and biochemical functions
250
Calcium:
| Failure to Maintain Homeostasis
intracellular calcium accumulation
calcium overload
cell death
251
Regulation of Extracellular Calcium
maintenance of homeostasis by diet and calcium and phosphorus
252
Vitamin D (1,25-dihydroxycholecalciferol)
synthesized in sebaceous glands of the skin via photoactivation of 7-dehydrocholesterol by UV light
subsequent conversion steps in the liver and then kidney form the fully active vitamin if there is a demand for calcium
253
Vitamin D:
| Stimulus
low extracellular calcium
| parathormone stimulates formation 1.25-dihydroxycloecalciferol by the kidney
254
Vitamin D:
| Main Action
'leads to increased extracellular calcium'
| principal action of vitamin D is to increase the absorption of calcium and phosphorus from the intestine
255
Parathormone
'parathyroid hormone'
synthesized by the endocrine (chief) cells of the parathyroid gland
mainly responsible for minute-to-minute regulation of extracellular calcium
256
Parathormone:
| Stimulus
low extracellular calcium
| elevated extracellular phosphorus
257
Parathormone:
| Main Actions
'lead to increased extracellular calcium'
increased mobilization of calcium from bone
stimulates formation of Vitamin D by the kidney, increasing absorption of calcium from the intestine
promotes resorption of calcium from the kidney
promotes excretion of phosphorus in the urine
258
Calcitonin
hormone is synthesized by the C-cells (parafollicular cells) of the thyroid gland
hormone antagonizes the effects of parathormone
259
Calcitonin:
| Stimulus
elevated extracellular calcium
260
Calcitonin:
| Action
'lowers extracellular calcium'
inhibits the parathormone-induced release of calcium from bone
promotes the urinary excretion of phosphorus
261
Dystrophic Calcification
occurs in dying and dead tissue
can't maintain calcium homeostasis
intracellular calcium levels increase
not as common in liquefaction tissue
262
Ischemia
accumulations of calcium in mitochondria
seen in dystrophic calcification
restriction in blood supply
263
Caseous Lymphadenitis
grossly visible calcification includes heart and skeletal muscles and caseating granulomas
264
Leukomalacia
'periventricular'
vitamin E/selenium deficiency
white matter brain injury
related to nutritional myopathy and cardiac necrosis due to drug toxicity
occurs in late term infants and common cause of cerebral palsy
265
Hypotension
causative factor (along with intrauterine infection) of leukomalacia
266
Calcinosis Circumscripta
large calcium deposits occur commonly at sites of persistent trauma such as boney prominences
have gross appearance of a tumor
'tumoral calcinosis'
267
Calcinosis Cutis
form of dystophic calcification
occurs in contet of hyperadrenocorticism
calcium deposits occur in collagen bundles and can be sufficiently severe
268
Cushing's Disease
hyperadrenocorticism
| result calcinosis cutis, a form of dystrophic calcification
269
Metastatic Calcification
associated with elevated extracellular levels of calcium exceeding homeostatic capacity of cells/tissues
specific tissues more prone to mineralization
involve vells and extracellular matrix components such as collagen in BM and elastic fibers in arterial walls
270
Metastatic Calcification:
| Locations
```
gastric mucosa-inner epithelial lining of the stomach
kidneys and lungs
cornea
systemic arteries
pulmonary veins
```
271
Calcium:
| Deposition
favors tissues with acid to alkaline interconversion
272
Hypercalcemia:
| Occurrence
hyperparathyroidism
hyper-vitaminosis D
diseases with extensive destruction of bone
273
Hyperparathyroidism
due to excessive production and secretion of parathormone or a parathormone-like substance
primary, secondary, or associated with a syndrome
274
Primary Hyperparathyroidism
excess production by parathyroid glands
due to hyperplasia and hypersecretion
production of excessive parathormone by parathyroid gland neoplasms
do not respond normally to negative feedback
275
Secondary Hyperparathyroidism:
| Nutritional
too much phosphorus in diet
prolonged feeding of grain-based rations
results in removal of calcium from bone causing bone disease as well
276
Bran Disease
due to prolonged feeding of grain-based rations high in phosphorus and low in calcium
277
Secondary Hyperparathyroidism:
| Renal
chronic kidney disease/renal failure
unable to excrete phosphorus and hyperphosphatemia develops
active form of vitamin D may not be synthesized by kidney
stimulates parathormone production
results in removal of calcium from bone so bone disease occurs also
278
Secondary Hyperparathyroidism:
| Paraneoplastic Syndromes
neoplastic cells produce substances not normal for the cell type
pulmonary epithelial cells do not normally produce parathormone
carcinoma lung cancer produces a metabolically active parathyroid hormone or parathyroid-like substance
produced by neoplastic lymphocytes and neoplastic epithelial cells
279
Lymphoma
parathyroid-like hormone produced by neooplastic lymphocytes resulting in hyperparathroidism
280
Apocrine Adenocarcinoma
parathyroid-like hormone produced by neoplastic epithelial cells in anal sacs of dogs resulting in hyperparathyroidism
281
Hypervitaminosis D
causes hypercalcemia by increasing absorption of calcium from intestines
from overzealous supplementation
some rodenticides can cause potent analogs
Cestrum diurnum and Solanum malacoxylon plants can cause
282
Destruction of Bone
significant cause of hypercalcemia and metastatic calcification in humans
primary (multiple myeloma) and metastatic cancers of bone can cause
283
Paget's Disease
'osteitis deformans'
hypercalcemia occurs
unknown cause
regions of osteoclastic bone resorption followed by period of hectic bone formation
284
Appearance of Soft Tissue Calcification
pathological calcification can only be detected frossly if extensive
pale chalky areas in the tissues
detected by coarse gritty feel
285
Intracellular Fluid
fluid withing cells
| makes up 41% of body
286
Transcellular Fluid Compartment
part of extracellular fluid
fluid in body cavities and eyes
makes up 5% of body
287
Intravascular Fluid Compartment
part of extracellular fluid
consists of vasculature, blood (plasma), and lymphatic vessels (lymph)
smallest compartment at 4%
288
Interstitial Fluid Compartment
part of extracellular fluid
bathes and surrounds cells
makes up 15% of body
289
Renin
hormone produced by juxtaglomerular apparatus in kidney
decreases blood flow (perfusion) to the kidney
may occur in reduction in cardiac output or decreased fluid volume in intravascular compartment
converts angiotensinogen to intermediate angiotensisn I
290
Juxtaglomerular Apparatus
in kidney
| produces renin
291
Angiotensinogen
plasma protein synthesized by the liver
| converted to intermediate angiotensin I by renin
292
Angiotensin I
intermediate of angiotensinogen converted by renin
| metabolized into antiotensin II by antiotensin converting enzyme
293
Angiotensin Converting Enzyme
found in endothelial cells lining blood vessels of the lung and kidney
converts angiotensin I into active form angiotensin II
294
Angiotensin II
active form
metabolized from angiotensin I by antiotensin converting enzyme
acts on aldosterone and vasopressin
net effect to increase fluid volume and blood pressure
restores renal blood flow and serves as negative feedback for renin secretion
295
Aldosterone
mineralocorticoid
296
Vasopressin
antidiuretic hormone, ADH
released from pituitary gland by stimulus from angiostensin II
increases passive pesorption of water from collecting ducts of the kidney, increasing fluid volume
use microfliaments and microtubules
297
Angiotensin II:
| Nervous System
increase activity of sympathetic nervous system
| positive inotropic and chronotropic stimulation of the heart to improve blood flow and blood pressure
298
Inotropic
force of muscle contraction
299
Chronotropic
rate of muscle contraction
300
Angiotensin II:
| Kidney
stimulates absorption of sodium and water from renal tubules
| increases fluid volume
301
Angiotensin II:
| Adrenal Gland
increase aldosterone secretion
increase absorption of sodium and water from the renal tubules increasing blood volume
extrusion of potassium into the tubule which is lost in the urine
302
Aldosterone
mineralocoricoid hormone secreted by zona glomerulosa of the adrenal cortex
303
Mineralocorticoid
class of steroid hormones that balance salt and water in the body
304
Addison's Disease
deficiency of aldosterone secretion
305
Angiotensin II:
| Pituitary Gland
stimulates release of antidiuretic hormone (vasopressin, ADH)
306
Colchicine
drug that treats familial Mediterranean fever
307
Diabetes Insipidus
due either to an absolute deficiency of ADH or to non-responsiveness of the kidney to the action of vasopressin/ADH
308
Angiotensin II:
| Blood Vessels
potent vasoconstrictor
elevates blood pressure
direct effect on the smooth muscle of arterioles
increases sympathetic nervous system activity
309
Atrial Natriuretic Factor
peptide hormone that controls fluid volume
synthesized and stored in granules within myocytes of the atrial myocardium
respond to distension of the atria by release of natriuretic factor (ATF)
antagonistic to other hormones
prevent resorption of sodium and water resulting in diuresis, decreased blood pressure, and inhibits secretion of renin, aldosterone, and vasopressin
310
Diuresis
increased secretion of urine
311
Intracellular Fluid Accumulation
hydropic change
swollen cells with clear, nonstaining cytoplasm
reversible, not all cells die, sometimes normal
312
Hydropic Change
when fluid is redistributed from the interstitial to the intracellular compartment
'intracellular edema'
313
Hypoxia
reduced dissolved oxygen levels
| due to failure of the energy driven sodium-potassium pump
314
Ischemia
restriction in blood supply
| due to failure of the energy driven sodium-potassium pump
315
Extracellular Fluid Accumulation
most dramatic fluid redistribution
| mostly interstitial and transcellular
316
Edema
accumulation of fluid due to redistribution from blood to interstitium that surrounds cells
317
Hydrothorax
fluid accumulation in chest
318
Hydroperitoneum
fluid accumulation in abdomen
| 'ascites'
319
Hydropericardium
accumulation of fluid in the membranous sac that surrounds the heart
320
Hydrocephalus
accumulation of excess fluid in the cerebral ventricular system
321
Hydrostatic Pressure
'blood pressure'
drives fluid from blood out of vasculature into the interstitial
balanced by osmolytes
322
Colloidal Osmotic Pressure
venous end
| osmolytes tend to return fluids to the blood vessels
323
Mechanisms of Abnormal Fluid Distribution
- increased vascular permeability
- increased intravascular hydrostatic pressure
- decreased intravascular colloidal osmotic pressure
- increased tissue colloidal osmotic pressure
- decreased lymphatic drainage
324
Increased Intravascular Permeability
occurs independent other forces
due to inflammation (localized or systemic)
blood vessels leak fluid and plasma proteins
325
Anaphylaxis
cause of increased intravascular permeability
326
Increased Hydrostatic Pressure
'hypertension'
increased pressure and increased permeability
results in redness and swelling
327
Congestive Heart Failure
increased hydrostatic pressure on venous side of circulation
hear not effective pump, backup of blood flow
ascites, hydrothorax, dependent edema of limbs
left-sided has pulmonary edema and hydrothorax
decreased renal perfusion, stimulates renin production, sodium retention, increase interstitial colloidal osmotic pressure
328
Decreased Intracascular Colloidal Osmotic Pressure
due exclusively to hypoproteinemia
alters fluid dynamic to redistribution
due to maldigestion, malnutrition, starvation, gastrointestinal parasitism, severe liver disease
329
Proteinuria
primary portal of protein loss from intestinal tract and kidney
330
Johne's Disease
caused by Mycobacterium avium, subspecies paratuberculosis
| inability to absorb protein from intestine due to inflammation
331
Increased Interstitial Colloidal Osmotic Pressure
neither primary nor dramatic
at sites of inflammation
sodium retention due to congestive heart failure
332
Decreased Lymphatic Drainage
blockage, leads to edema
can be blocked at level of lymphatic vessels or can occur from total obliteration of lymph nodes that are situated along the course of these vessels
accumulates in interstitium
333
Lymphedema
lymphatic obstruction
334
Abscesses
caused by thin walled lymph vessels and can be compressed at sites of infalmmation and space occupying masses
335
SIADH:
| Syndrome of Inappropriate Antidiuretic Hormone (ADH) Hypersecretion
results in hypervolemia
| increases absorption of water from tubules but not ions resulting in hypertonic urine
336
Hyponatremia
from SIADH
| increased absorption of water with ions left behind creating hypertonic urine
337
Meningitis
also have SIADH
338
Iatrogenic
administering fluids intravenously can result in hypercolemia if done too fast or whenn kidneys are comprised and urine production is poor
may manifest as rapidly developing pulmonary edema
339
Idiopathic/Idiosyncratic Water Drinkers
polydipsia
may be due to faulty regulation of thirst
hyponatremia can be a complication
340
Hypovolemia/Dehydration
reflect too little body water
| inadequate intake of fluid to match loss
341
Causes of Hypovolemia
```
insufficient water intake
increased loss due to kidney disease
vomiting/diarrhea
hyperhidrosis/hyperpnea
drugs
diabetes insipidus
hypoadrenocorticism (Addison's disease)
```
342
Insufficient Water Intake
basal urine output is minimum amount of water that must be ingested
ambient temperature, physiological states, physical exertion modify daily needs
salt poisoning due to dehydration
343
Increased Loss due to Kidney Disease
causes loss of specific gravity in urine, level of solutes in urine, and ability to conserve water
low urine specific gravity is sign of kidney disease
results in polydipsia-polyuria cycle
344
Vomiting/Diarrhea
results in significant water loss
loss of H+ resulting in alkalosis
loss of ions such as Na+ and Cl-
345
Drugs
mainly diuretics that increase urine production
346
Diabetes Insipidus
due to deficiency of antidiuretic hormone (pituitary dependent)
due to failure of kidney to respond to ADH (nephrogenic)
brain disease such as inflammation and space occupying masses that prevent storage and release of ADH from pituitary gland
due to polycystic kidney disease, renal amyloidosis, lithium, hereditary causes
aquaporin-2 gene mutation recessive
347
Hypoadrenocorticism (Addison's Disease)
typically due to destruction of the adrenal cortex
adrenal cortex produces cortisone (glucocorticoids) and aldosterone (mineralocorticoid)
due to deficiency in aldosterone
renal tubules are unable to absorb and conserve sodium and water
can create hyponatremia
348
Sequence of Events in Dehydration
1) initial loss of interstitial fluid w/ redistribution to blood to maintain blood volume
2) loss of intracellular fluid to maintain blood volume
3) hyperviscosity of blood and generalized hyperosmolar state
- mainly affect cardiovascular and brain
- heart has difficulty pumping
349
The Brain During Dehydration
mechanisms to protect against osmotic imbalances
hyperosmolarity used to measure context of blood sodium
hypernatremia
350
Brain Dehydration:
| Acute Phase
1-2 days
brain attempts to correct by eliminating ions
brain shrinks
death at this stage and the principal lesion that may be seen as hemorrhage due to tearing of blood vessels in the meninges
351
Brain Dehydration:
| Chronic Phase
3+ days
ionic balance critical for neuronal activity
attempts to restore balance by production of organic osmolytes (such as glutamine, glycine, phosphoinositol)
offset osmotic dysequilibrium for more normal ionic balance
death may occur at this stage
352
Brian Dehydration:
| Dangers of Rehydration
fluid volume increases rapidly in intravascular compartment but brain takes time to eliminate osmolytes
if happens to fast, gradient established and fluid moves from blood to the brain causing brain swelling causing serious brain damage and death
353
Pigment
any normal or abnormal coloring (matter) of the body
354
Melanin
brown pigment coloring skin, iris, freckles (lentigines)
synthesized from the amino acid tyrosine in cells called melanocytes
copper deficiency dilutes melanin
355
Hypomelanosis
too little melanin pigmentation
| can be hereditary or acquired
356
Melanocytopenic Hypomelasnosis
herediatary disease where there is an absence of melanocytes
357
Waardenburg Syndrome
due to defective migration of cells from the neural crest, including cells destine to be melanocytes
hypomelanosis, a patch of white hair, deafness
358
Hirschprung Disease
'Waardenburg syndrome type IV'
| failure of the sympathetic nervous system to develop in the lower large intestine
359
Melanopenic Hypomelanosis
hereditary disease
melanocytes present but fail to produce melanin
can be due to a variety of causes including copper deficiency or autoimmune destruction of melanoytes
360
Albinism
due to absence or a defect in the tyrosinase gene
| form of melanopenic hypomelanosis
361
Hypermelanosis
too much melanin
362
Malanosis
refers to presence of melanin pigmentation where not normally present
363
Hypermelanosis:
| Neoplasm
melanocytoma (benign) or melanoma (malignant)
most common in the skin
associated with exposure to UV light
364
Carcinogenesis
multistep process involving multiple genetic abnormalities that alter the proliferation of cells, interfere with DNA repair, prevent programmed cell death
allows abnormal cells to live and continue to proliferate
365
Apoptosis
programmed cell death
366
Lipofuscin
```
yellow-brown
accumulates in the cytoplasm of cells
formed during autophagy
age-related 'wear-and-tear' pigment
most common in permanent and stable cells
```
367
Autophagy
process that digest effete organelles over the life of the cell
368
Neuronal Ceroid Lipofuscinoses
hereditary neurodegenerative disorders
lysosomal storage disease
chemically complex, consist of lipids, amino acids, autofluorescent
369
Neuronal Ceroid Lipofuscinoses:
| Main Syndromes
based on age of onset, clinical course, pathology
- infantile (Haltia-Santavouri Disease)
- late infantile (Jansky-Bielschowsky Disease)
- late juvenile (Batten-sielmeyer-Vogt Disease)
- adult onset (Kuf's Disease)
370
Porphyrias
'purple pigment'
develops when there are defects in the pathway of heme synthesis resulting in a buildup of potentially toxic heme precursors
371
Photosensitization
photoactive precursors in the heme synthetic pathway accumulate leading to blistering of the skin after exposure to sunlight
372
Hepatogenous Photosensitization
photosensitization in herbivores secondary to sever liver disease due to failure to excrete the photoactivated chlorophyll catabolite phylloerythrin
373
Phylloerythrin
photoactivated chlorophyll
| failure to excrete results in hepatogenous photosensitization
374
Hemosiderin
converted from heme iron by macrophages
375
Biliverdin
degraded from remaining heme molecule
376
Hemolytic Anemias
increased destruction of erythrocytes in diseases
377
Siderophages
macrophage
| accumulates hemosiderin at sites of hemorrhage
378
Hemosiderosis
accumulation of hemosiderin at sites of hemorrhage in spleen and liver
379
Herediatry Hemochromasosis
accumulation of heme iron
defective transport of iron and increased absorption of iron from the intestine
massive accumulation of iron in tissues causing brownish color
most severe in liver, leads to necrosis, scarring, cirrhosis
380
Secondary Hemochromatosis
people receiving repeated blood transfusions
381
Biliverdin/Bilirubin
formed enzymatically in macrophages
bruise colors (blue, green, yellow)
bilirubin is released from macrophages, enters blood, complexed with albumin, dissociates in liver
in the hepatocyte cytoplasm glucuronic acid is enzymatically attached to form conjugated bilirubin and bilirubin glucuronide and excrete in bile
382
Hyperbilirubinemia
increase of bilirubin in the blood either conjugated or unconjugated
383
Jaundice/Icterus
yellow discoloration of tissues due to hyperbilirubinemia
| sign of increased erythrocyte destruction, liver disease, or blockage in flow of bile from hepatoytes to bile ducts
384
True Statement Regarding Cells Types
permanent cells are not capable of cell division and are more likely to respond to sublethal injury by hypertrophy
385
Briefly Explain the Major Defference Between Atrophy and Hypoplasia
atrophy: acquired decrease in size of a cell, tissue, or organ
hypoplasia: congenital decrease in size of a cell, tissue, or organ
386
Mechanism the Best Described the Intracellular Accumulation that Ocurs in Lysosmal Storage Disease
accumulation of normal endogenous substances due to faulty catabolism
387
Explain the Pathogenesis of Reactive Systemic Amyloidosis
1) chronic inflammatory disease states with some non-immunocytic neooplasms
2) the liver synthesizes increased levels of a protein, serum amyloid A (SAA)
3) proteolytic cleavage results in the fibril protein AA deposited in various tissues
388
Define/Explain Difference Between Dystrophic and Metastatic Calcification
- dystrophic occurs in dead, dying tissue, hypercalcemia not required
- metastatic occurs in viable tissue, hypercalcium required
389
Explain the Pathogenesis of Pathological Calcification in Vitamin D Poisoning
hypervitaminosis D leads to hypercalcemia and then to metastatic mineralization
390
What is the Difference Between Melanocytopenic and melanopenic Hypomelanosis
- deficiency of melanocytes (vitiligo/Waardenburg)
| - defective melanin production (albinism)
391
Statement Regarding Hemochromatosis
-massive iron accumulation in the liver leading to liver disease
