Intro to Pathology Flashcards
(249 cards)
1
Q
What is pathology?
A
study of suffering
2
Q
What is a pathologist
A
trained in diagnosis of disease on the gross, microscopic and ultrastructural level
3
Q
what is thanatology?
A
study of death
4
Q
What does thanatology involve?
A
1) signs of death 2 agonal and postmortem processes 3) exam of corps/carcasses 4) determination of cause of death 5) determination of manner of death 6) determination of mechanism of death; final common pathways of death
5
Q
What is agony?
A
1) transition time from life to death
2) loss of fn and coordination of respiratory system, CV and CNS –> generalized organ dysfunction
6
Q
Describe different time durations of agony
A
1) very short: seconds - gun shot wound to heart
2) short: minutes - exsanguination from liver rupture
3) hrs: neoplastic diseases
7
Q
Define cause of death
A
disease or injury responsible for the terminal lethal sequence of events
- may include a root and an immediate cause
- is as specific as possible
8
Q
Give an example of a root and an immediate cause
A
root: husbandry
immediate: marked acute fibrinous pleuropneumonia
9
Q
Define mechanism of death
A
alterations of physiology and biochemistry whereby the cause of death exerts its lethal effect (final terminal events)
-etiologically unspecific
10
Q
What are the types of “manner of death”
A
natural, non-natural (or violent) or undetermined
11
Q
What are violent manners of death?
A
accident, homocide, suicide
12
Q
What are the types of death?
A
somatic and cell death
13
Q
what are the death marks?
A
rigor mortis, pallor mortis (paleness), algor mortis, livor mortis, decomposition, skeletonization/mummification
14
Q
What is death defined as?
A
absence of vital signs
- brain death
- permanent vegetative state
15
Q
What are the 4 aspects of the disease process?
A
etiology = why
pathogenesis = how
morphologic changes
clinical significance
16
Q
Define etiology
A
the science or study of causation (some form of noxious stimulus)
-cause or causative factor
17
Q
Define pathogenesis
A
mechanisms of disease or sequence fo events in the development of a lesion, clinical signs, from inception/initial stimulus to resolution
18
Q
What are morph changes?
A
structural alterations in cells or tissues characteristic of disease or diagnostic of etiology
19
Q
What is clinical significance?
A
functional consequences of morphologic changes
20
Q
What is pathology essentially?
A
study of lesions
-structural and/or functional changes associated with disease
21
Q
What is a lesion?
A
any departure from normal; abnormality in the tissue
-postmortem/euthanasia artifacts vs lesion
22
Q
Define necropsies
A
systematic examination of a corpse or carcass for lesions by a vet or vet pathologist
23
Q
What are some postmortem artifacts?
A
autolysis, scavenging, postmortem clots, rigor mortis, bloody imbibition, biliary imbibition, pseudomelanosis
24
Q
define autolysis
A
putrefaction; inc temp, imc autolysis
25
define bloody imbibition
leakage of vessels
26
define biliary imbibition
gallbladder leaks - greenish coloring
27
define pseudomelanosis
hemorrhage under influence of bacterial enzymes: turn red --> black
28
what are euthanasia artifacts?
deposition of crystallized barbiturates
| -spleen congestion
29
What are agonal lesions?
pulmonary congestion and edema; hypostasis
30
what is hypostasis?
pooling of blood on dependent side (in lungs or kidneys)
31
What are incidental lesions?
lesions that do not cause any clinical disease - can predispose the animalt o clinical signs under certain circumstances
32
What are the characteristics of lesions?
1) location
2) shape (symmetry)
3) size
4) color
5) consistency
6) appearance of cut surface
7) odor
8) taste
33
What is a diagnosis?
concise statement or conclusion concerning the nature, cause or name of a disease as determined from careful investigation of the signs/symptoms and history (evidence based)
34
What is the accuracy of a diagnosis limited by?
history provided and the evidence (lesions) available for study
35
What is a clinical diagnosis?
based on the data obtained from the case history, clinical signs/symptoms and physical examinations
-may only suggest the system involved and usually supplemented by a list of differential diagnoses
36
What is a differential diagnosis?
the "rule outs" in clinical medicine; a list of diseases that could account for the evidence or lesions of the case
37
what is the clinico-pathologic or anatomo-pathologic diagnosis?
based on changes observed in the chemistry of fluids and the structure and function of cells collected from the living patient (smears, aspirates, biopsies)
38
What is a morphologic diagnosis?
lesion diagnosis - based on predominant lesions in tissues
| -addresses the severity, duration, distribution, location, and nature (degenerative, inflammatory, neoplastic)
39
What are morphologic differential diagnoses?
lesion that looks similar or alike
40
What is an etiologic differential diagnosis?
agents/processes that cause same or similar lesions
41
define etiologic diagnosis
even more definitive and names the specific cause of the disease
(only get this by culturing, need fresh tissue)
42
define disease diagnosis
equally specific as etiologic diagnois and states the common name of the disease
43
What are the two causes of disease?
endogenous (intrinsic) = genetic/certain malformation or immunologic factors
exogenous (extrinsic/acquired) = physical or chemical noxes, alimentary causes, infectious organisms
44
genetic causes of disease
heritable = mutation in germline cells --> can be passed on to offspring
inheritable = mutation in somatic cells --> passed on to subsequent generation of cells but NOT to offspring
-spontaneous or caused by env factors
45
Name the types of mutations
1) single gene
2) genome (numeric chromosomal alterations)
3) chromosome (structural chromosomal alterations)
4) complex multigenic disorders
46
Name the consequences of point mutations
1) silent mutation = doesn't alter AA seq of protein
2) Missense mutation = single AA change seq
3) nonsense mutation = produces stop codon in mRNA --> terminates tln of protein
47
Consequences of single gene missense or nonsense?
1) formation of abnormal protein
2) reduced or increased synthesis of protein
3) modification of postranslational mechanisms, or transport of proteins out of cell
48
What types of proteins can be affected?
1) enzymes --> accumulation in cell or lysozome
2) membrane receptors and transporters --> accumulation
3) non-enzyme proteins --> structural
4) unusual drug reactions --> multi-drug resistant gene
49
What are the effects of an enzyme defect?
1) accumulation of substrate (storage disease)
2) metabolic block (lack/deficiency of substrate for norm cell fn)
3) failure to inactivate tissue damaging factors
50
give example of autosomal dominant trait
PSSM
51
give ex of autosomal recessive trait
LWFS
52
give ex of x-linked disorder
hemophilia
53
What are chromosomal disorders
numeric alteration of set of chromosomes (genome mutation)
- entire set may be altered (aneuploidy)
- only the number of inidividual chromosome is altered (down syndrmoe - trisomy 21)
54
how are chromosomal disorders created?
structural alteration of chromosome by deletion, inversion, isochromosome fomration, translocation
-usually sex chromosomes affected --> intersex
55
What are complex multigenic/polygenic disorders?
caused by interactions of multiple genes and environmental factors
-disease only occurs when multiple polymorphisms occur simultaneously and certain env factors are present
56
What are the contributing factors of disease?
disposition, constitution and conition
57
What are the two types of dispositions?
genetic (species, breed, family, gender, individual) and acquired (nutrition, occupation, age)
58
Define constitution
sum of inherited and acquired dispositions of an individual
| -marked individual and temporal variations
59
Define condition
sum of acquired dispositions of an individual influenced mainly by external factors (training, nutrition, climate, hygiene)
60
What are the different physical noxious stimuli?
trauma, temperature, actinic,electricity, climate
61
Describe different types of trauma
1) sharp force injury and gun shot wounds (organ perforation, fractures, exsang)
2) blunt force trauma (distorsion, fractures, dislocation, laceration, contusion)
3) local effects (local infections)
4) systemic effects (anemia, woundd shock, hyperkalemia, bone marrow emboli to lungs (after bone fracture), generalized infection)
62
define wound shock
loss of fluid due to histamine release in damaged tissue (aggravates blood loss)
63
define hyperkalemia
release of intracellular potassium from large number of lethally injured cells --> arrhythmias
64
define crush kidneys
reduced blood supply to kidneys plus increased amt of myoglobin (toxic effect on renal tubules) form damaged muscle cells flooding kidney --> insufficient blood supply; degenerative change in kidney
65
describe different types of temperature physical noxious stimuli
hyperthermia (often in combo ith strenuous exercise), combustio, hypothermia, congelatio
66
describe consequences of hyperthermia
1) denaturing of protein because of heat
2) dehydration due to fluid and electrolyte loss (sweating)
3) vasodilation in skin and vasoconstriction in internal organs --> hypovolemia
4) Heat shock --> DIC, disseminated intravascular coagulation (head exposed to direct heat -->brain overheated, BT norm)
67
describe combustio
burn(dry heat)/scold(hot liquid)
- everything sloughing off because of over exposed sun (reddening of skin)
- animal may burn to death or after burn
68
describe hypothermia
<95 degrees F - not enough blood supply to brain
69
describe congelatio
freezes, damage to internal structure
70
describe different types of actinic
visible sunlight/UV light and ionizing radiation
71
describe visible sunlight/UV light as a noxious stimuli
damaging after photosensitization occurs = presence of photodynamic comp in skin --> damage to non-haired non-pigmented skin regions
-sun burn --> sq cell carcinoma
72
describe types of ionizing radition
- local radiation versus full body radiation, oral uptake
- x-rays, gamma rays
- mitotic active cells and water containing tissues are highly vulnerable
73
Describe different types of photosensitization
1) primary = uptake of photodynamic compounds with food (plants) --> depositio in skin
2) secondary = inherited defect in porphyrin metabolism; aberrant porphyrin metabolites are photodynamic and deposited in skin
3) hepatogenic = only in ruminants;phylloerythrin persists in circulation in animal with liver disease and is deposited in skin
74
What are the consequences of acute total body radiation?
1) central nervous syndrome - death within minutes to hrs, vomiting, cramping,
2) lymphopenia
3) gastro-intestinal syndrome - death w/in 2 wks
4) hematopoietic syndrome - may need bone marrow transplant
5) subclinical or prodromal sndrome - patient can recover
75
What are some skin reactions as a result of ionizing radiation?
1) Epilation (1deg) = loss of keratin and depigmentation of skin and hair
2) Erythema (2deg) = dermatitis, hair loss, depigmentation of re-growing hair
3) Exudate (3deg) = exudative dermatitis with blisters and crusts and permanent alopecia
4) Necrosis and poorly healing ulcers (radiation dermatitis)
76
What are some chronic consequences of ionizing radiation?
1) cancer - leukemia, thyroid, mammary, pulmonary and salivary gland carcinoma, skin cancer
2) Fibrosis - radiation-assoc vasculopathy (hypoperfusion)
3) Others: lymphopenia, infertility (gonad atrophy), cataracts, impaired wound healing
77
What are examples of electrical noxious stimuli?
1) household current - burns, arrhythmia
2) lightening strike
3) power line collisions in birds
78
What are examples of climate noxious stimuli?
1) slow dec in atm pressure and [oxygen], high altitude disease
2) sudden dec in atm P - diver disease
3) sudden inc in atm P (explosion) - pulm hemorrhages
79
What are chemical noxes?
toxins - intoxications (poisoning; exogenous and endogenous
80
How do chemical noxes get into your system?
oral, percutaneous, inhaled, into blood stream (bite)
81
What are exogenous toxins?
1) environmental toxins (lead, mercury)
2) plant toxins (alkaloids, glycosides)
3) Animal toxins (venom)
82
What are endogenous toxins?
by product of metabolism - ammonia, ketones, urates
83
What are toxins made up of?
antigenic and toxiphoric groups
84
What factors influence toxic effects
1) dependent on concentrations
2) route of up-take
3) frequency of up-take
4) toxins must be soluble to be absorbed by cells or at least adherent to cells
85
What are some effects of toxins?
1) cytolysis, altering enzyme activity and cell metabolism
2) biochemical mechanisms (toxify in liver)
3) acute toxicoses vs chronic toxins (carcinogens)
4) reversible vs irreversible effects (cells affected must die off and be replaced)
5) local irritation on skin, alimentary tract and respiratory tract or systemic effects (cardiotoxic, nephrotoxic, hepatotoxic, neurotoxic)
86
What are host defense mechanisms against toxin?
reflexes, elimination and metabolism in the liver
87
What are some pathologic anatomic findings of intoxication?
some have pathogenomic lesions but most have no or unspecific findings
88
How do you test for toxins?
history, CSI, chemical analysis (gastric content, liver, kidney, urine, blood, brain, adipose tissue) - depends on toxin type and time course
89
What are two ways of testing nutrition?
1) quantitative: emaciation (cachexia - def syndrome) and obesity (def)
2) qualitative (hyper/hypo-vitaminoses): lack of essential factors, reduced enteric absorption or presence of capture mols or antagonistic/competing cmpds in food
90
What is a common nutrition pathology?
mineral element deficiency
91
What are mineral elements function?
serve mainly as co-enzymes, regulation of pH in intra and extracellular milieu, and bone formation
92
Give some examples of mineral element deficiencies
1) rickets (P def)
2) tetany (Mg def)
3) milk fever (Ca def)
4) white muscle disease (selenium/vit E def)
5) milk anemia (Fe def)
93
What are the two types of vitamin pathologies?
1) hypovitaminoses (and avitaminoses) - K, A, B1 - due to primary thiamin def or due to presence of thiaminases
2) Hypervitaminoses (fat soluble vits) - A (due to liver diet in cat) and D (iatrogenic)
94
What is dehydration?
lack of water, loss of water (and Na), loss of Na, loss of water via kidney
95
What's the cause of loss of water (and Na)?
1) diarrhea and vomiting
96
What's the cause of loss of sodium?
due to deficient Na reabsorption of renal tubular epithelial cells in acute renal failure (hypotone dehydration)
97
What's the cause of loss of water (not Na) via kidney?
diabetes insipidus and mellitus --> hypertone dehydration, PD
98
What is hyperhydration?
increased infusion of fluid, often iatrogenic
99
What are the different types of hyperhydration?
1) isotone = rate of hydration with physio soln is higher than renal excretion
2) Hypertone = due to inc Na up-take or dec Na excretion in animals with renal insufficiency (inc water excretion)
3) Hypotone = due to infusion with too much hypotone soln, dec water excretion in animals with renal insufficiency --> pulm edema, ascites (accum of clear fluid in abdominal cavity), hydrothorax, brain edema
100
What is parasitism? ex?
negative effect for host; virus, bacteria, fungi, parasite
101
What is an infection?
colonization, attachment, invasion and proliferation of obligate or facultative pathogenic parasite
-infection does NOT equal inflammation
102
What may infection result in?
- local or generalized infection
| - disease or clinically inapparent
103
Can local infection become generalized?
yes
104
Give examples of generalized infection?
1) cyclic course
2) septicemia/sepsis
3) virus induced tumor disease (leukemia)
4) diseases due to infection-assoc immune modulation
5) factor diseases and mixed infections
105
What are some causes of diseases? (immunologic reactions)
1) immune response - cells damaged in immune response to infectious agents
2) hypersensitivity (allergic) rxns - anaphylactic rxn to a foreign protein or drug
3) autoimmune diseases - rxn to self-antigen
106
cells encountering physiologic stresses or pathologic stimuli can undergo___ to achieve ________
adaptation, homeostasis
107
What happens when cells can't maintain homeostasis?
cell injury (demands exceed adaptive capability)
108
Where are cells embedded in?
extracellular matrix
109
Whats the fn of cytoskeleton? describe the different types?
transport of substances through the cell
| microfilaments, intermediate filaments, microtubules
110
What is reversible cell injury?
cell degeneration
111
What does irreversible cell injury lead to?
necrosis
112
What are causes of reversible and/or irreversible cell injury?
O2 deficiency, physical agents, infectious agents, nutritional deficiencies and imbalances, genetic derangement, workload imbalance, chemical drugs and toxins, immunologic dysfunction, aging
113
What is the progression of pathological changes with cell injury?
after 6 hrs - 1st lesions often on ultrastructure
after 12 hrs - changes in cell (cell membrane)
another day or so - gross changes
114
Describe mechanisms of cell injury
- dec ATP --> dec cell function
- membrane and organelle membrane damage:
- ->lysosome --> leakage --> self digestion
- ->mito --> cell death
- ->plasma membrane --> lose cell contents, influx of other comp
- inc intracellular Ca+2/ROPs --> DNA damage and protein breakdown
115
What intracellular systems are highly vulnerable to cell injury?
1) cell membranes
2) aerobic respiration (mito)
3) protein synthesis (ER)
4) genetic apparatus
5) cytoskeleton
116
Define reversible cell injury (cell degen)
cell undergoing functional and morphologic changes as a result of injury --> if stimulus is removed in time, changes resolve (cells can still regenerate)
-once pass certain point, injury becomes irreversible --> cell death
117
name characteristics of irreversible cell injury
reduced oxidative phosphorylation --> ATP depletion (Na/K ATPase) --> cellular swelling (Na remain in cell and osmotically active --> inc water into cell --> organelles swell)
118
Whats another name for cellular swelling?
cell edema
119
What is cell swelling?
disturbance of cellular water balance; increased cell size and volume resulting from an overload of water (hyperhydration)
-most common and fundamental expression of cell injury
120
What causes cell swelling?
failure of cell volume regulation --> swelling, modification and degeneration of organelles
121
What is hypoxia?
reduced oxygen partial pressure in blood or tissue
122
What is ischemic hypoxia?
decreased circulation of tissue in terminal capillary bed
123
What does ischemic hypoxia result in?
O2 deficiency, dec delivery of nutrients and decreased removal of cytotoxic metabolites
124
What can happen to cells who experience ischemic hypoxia?
cells may adapt to mild ischemia (muscle atrophy) or die with severe and sudden onset ischemia
125
What is infarction?
localized area of ischemic necrosis (coagulation)
126
What is anemic hypoxia?
decreased oxygen carrying capacity of blood
127
define hypoxemic hypoxia
respiratory insufficiency (insufficient O2 to lungs), high altitude, crowding in closed rooms
128
define histiotoxic hypoxia
oxidative cellular metabolism is impaired (due to toxic insults such as cyanide toxicity)
129
define hypoglycemic hypoxia
lack of glucose/substrate for oxidation
130
when does hypoxia occur?
reduced amts of saturation of hemoglobin ( really any defect in O2 transportation)
131
When does ischemia occur?
mechanical obstruction in the arterial system (thrombus or embolus)
-catastrophic fall in BP (loss of blood)
132
What is the difference btw hypoxia and ischemia?
hypoxic conditions - glycolytic energy production can occur
-in ischemia - even delivery of substrates needed for glycolysis and disposal of toxic/injurious metabolites are compromised
133
What does tissue sensitivity to hypoxia depend on?
demand of cells (exercise vs sleeping)
134
What tissues are highly/intermediate/low susceptible to hypoxia?
```
high = neurons
intermediate = hepatocytes, cardiomyocytes, renal and intestinal epithelium
Low = fibroblasts, keratinocytes, myocytes
```
135
What are gross lesions?
organ swelling and pallor (enzyme leakage into blood stream); organ changes that are caused by degenerative changes end with "osis"
136
What is dystrophy?
disease that is caused by degenerative changes due to deranged cellular metabolism
137
What is the morphology of cell swelling?
1) cell is enlarged
2) nucleus normal position
3) cytoplasm pale or staining altered
- cloudy; vacuolar degeneration - swollen organelles; hydropic degneration - ballooning degen
138
What are common consequences of hypoxic and toxic injury?
depletion ATP, decreased ATP synthesis
139
What results from dec ATP/ATP synthesis?
inc AMP --> inc anaerobic glycolysis --> inc lactic acid --> dec intracellular pH --> impaired cell enzyme activity
140
T or F: cells with greater glycolytic capacity have an advantage over cells which are more or exclusively reliant on oxidative phosphorylation
True
141
What are cytomorphologic changes of irreversible cell injury?
1) plasma membrane damage
2) Ca entry into cell
3) mito swelling and vacuolization
4) lysosomal swelling
142
What's another name for oxidative stress?
Free radical induced injury; common cause of damage to cell membranes
143
Describe different ways to generate free radicals
1) Cell metabolism (byproduct) - cell redox rxns
2) Enzymatic metabolism of exogenous chemicals (drugs)
3) ionizing radiation - hydrolysis of water into OH and H free radicals
4) Divalent metals - transition metals, catalyze free radical formation, free radicals
144
What are characteristics of free radicals?
extremely unstable, readily react with organic or inorganic cmpds, attack and degrade proteins/nucleic acids and membrane mols
145
define oxidative stress
cell injury occurs when the free radical generation overwhelms radical-scavenging defense mechanisms
146
What are main sites of damage for free radicals?
membranes (cause instability - lipid peroxidation), proteins (structural damage), DNA (cause breaks)
147
the cell's response to injurious stimuli depends on?
type of injury, duration and severity
148
the consequences of cell injury depends on?
type, state and adaptability of injured cell
149
When irreversible ischemic injury persist?
if ischemia persists
150
What are two characteristics of irreversible ischemia?
1) inability to reverse mito dysfunction
| 2) profound disturbances of membrane function
151
What is the sequence of events in a cell injury?
1) Hypoxia - deficiency of O2
2) decrease of oxidative phosphorylatin and then ATP
3) increased glycolysis, increased intracellular lactate (dec pH) and depletion of glycogen stores
4) failure of Na/K pump due to ATP deficiency
5) Net influx of Na, Ca and water with loss of intracellular K and Mg
6) swelling of mito, the cytocavitary network and nucleus
7) detachment of ribosomes, clumping of nuclear chromatin, loss of microvilli, vesiculation of ER
8) severe disruption of cell membranes, influx of Ca into mito and cytosol, overall cell enlargement, release of lysosomal enzymes and clearing of the cytosol
9) irreversible cell injury, cell death
152
What are types of cell death?
1) oncosis - cell death due to a lethal insult
2) apoptosis = programmed/genetically controlled cell death due to a suicide signal
3) autophagia
153
What is oncotic necrosis?
severely damaged membranes --> lysosomal enzymes enter cytoplasm --> digest cell --> cellular contents leak out
154
define necrosis
distinctive morphologic patterns depending on whether enzyme catabolism or protein denaturation predominates
155
What are morphologic patterns of necrosis?
Coagulation, liquefactive, casous, gangrenous and fat necrosis
156
What is coagulation necrosis?
most common manifestation of cell death; characteristic of hypoxic/ischemic death of cells in all tissues
- protein denaturation predominates over enzymatic digestion
- injury/intracellular acidosis denatures enzymatic proteins --> blocks proteolysis
- brain has a lot of fat
157
What does coagulative necrosis appear grossly?
- architecture resembles normal tissue
- lighter in color (coagulation of cytoplasmic proteins and decreased blood flow)
- usually firm
- tissue may be swollen or shrunken
- may see a local vascular/inflammatory rxn to necrotic tissue
158
How does coagulative necrosis appear microscopically?
- original cell shape and tissue architecture preserved
- increased eosinophilia
- hyalinized (glassy appearance)
- vacuolated cytoplasm
- may be mineralized
- shrunken basophilic nucleus
- nuclear fragmentation
159
What are cytoplasmic changes in dead cells?
- loss of differential staining characteristics of nucleus and cytoplasm (eosinophilia)
- massive swelling of cells and organelles with fragmentation
- loss of cell to cell contact
- loss of microvilli and cilia
160
What is liquefactive necrosis?
enzymatic digestion of necrotic cell predominates
161
When does liquefactive necrosis occur?
- in bacterial infections (neutrophils contain potent hydrolases)
- in hypoxic damage of CNS
162
What does liquefactive necrosis appear grossly?
affected tissue is liquefied to a soft, viscous fluid mass
163
What does liquefactive necrosis appear microscopically?
may see degenerative neutrophils and/or amorphous necrotic material
164
When does caseous necrosis occur?
seen with specific bacterial diseases
165
How does caseous necrosis appear grossly?
cheesy; grey white dry, friable to pasty necrotic material; freq with dystrophic calcification
166
How does caseous necrosis appear microscopically?
dead cells persisting as amorphous, coarsely granular eosinophilic debris
- necrotic cells do not retain cellular outline
- necrotic cells do not undergo complete dissolution
- freq association with granulomatous inflammation and thick outer fibrous capsule
167
What is gangrenous necrosis?
ischemic necrosis of extremities; gangrenous inflammation = aspiration penumonia and gangrenous mastitis (very malodorous)
168
What is dry gangrene?
coagulation necrosis of an extremity with subsequent mummification
169
What is wet gangrene?
when the coagulative necrosis of dry gangrene is modified by the liquefactive action of saprophytic/putrefactive bacteria
170
what is gas gangrene (emphysematous)?
clostridial infections with necrosis and gas production
171
How is fat necrosis distinguished?
by its location in body fat stores
172
What is the cause of fat necrosis?
inflammation, Vit E deficiency, trauma, idiopathic
173
How does fat necrosis appear grossly?
firm to hard, white/chalky and gritty areas; can be soft
174
How does fat necrosis appear microscopically?
ares of necrosis of fat tissue
| -see basophilic calcium deposits and often surrounded by inflammatory cells
175
What is hemorrhagic necrosis?
necrosis + hemorrhage;
- usually when venous outflow to tissue is blocked
- hemorrhagic infarction of bowel
176
What is fibrinoid necrosis?
vasculature affected
- freq found in auto-immune disease but also in lead toxicosis
- histo: eosinophilia and hyaline appearance of media of vasculature
177
What are consequences of necrosis?
- biochemical changes: leakage of tissue specific enzymes; detectable in serum
- Inflammation: beginning at transition of necrotic to healthy tissue
178
What is the outcome of necrosis?
1) restitutio ad integrum (regeneration with restoring of normal fn)
2) reparation (scarring, healing without restitution)
3) Demarcation (including sequester formation/sequestration)
179
What factors must be present in order for regeneration to occur?
- if damage was minor
- if texture of tissue was maintained
- if affected tissue/individual has good healing capacity
180
What happens with demarcation of necrosis?
- necrotic tissue is surrounded by area of inflammation (reddened)
- shedding of damaged tissue in skin and mucous membranes (ulcer)
- sequester in lung and bone (with fistulous tract)
181
What is apoptosis?
programmed cell death; nuclear dissolution without loss of membrane integrity; cell dies thru activation of an internally controleld suicide program; may be physiologic or pathologic
182
What are causes of apoptosis?
1) cells undergoing programmed cell death during embryogenesis
2) cells undergoing normal turnover (cell deletion in proliferating pop)
3) immune system (deletion of autoreactive T cell clones in thymus)
4) cell death in neoplasms
5) pathogenic stimuli (viruses, immune-mediated processes)
183
What are mechanisms of apoptosis?
genetically determined, energy-dep sequence of molecular events of initial cell signaling (initiation phase), regulation by regulatory mols, (execution phase) and dead cell removal (phagocytosis
184
describe the two pathways of apoptosis
- extrinsic pathway = receptor-initiated, ligand-binding, initiator capase
- intrinsic pathway = mitochondrial pathway; if cytochrome c is released and other members join --> activation of caspases and executioner caspases; pro=Bak mol, anti=Bcl mol --> which side has larger [ ] of mols dictates end result
185
What is the execution phase of apoptosis?
proteolytic cascade that ultimately results in activation of the execution caspase 3 or 6
186
What is a caspase?
C=cysteine enzyme
aspase=capability to cleave aspartic acid residues
-exist as proenzymes (zymogens) and needs to be cleaved for activation
187
What does a caspase do?
cleave proteins of cytoskeleton and nuclear matrix, proteins involved in txn and tln process, proteins of DNA repair machinery
188
Describe the morphology of apoptosis
1) cell shrinking
2) chromatin condensation
3) Formation of cytoplasmic blebs than apoptotic bodies
4) phagocytosis of apoptotic cells/bodies
189
Describe main differences btw apoptosis and cell necrosis pathways
-both programmed cell death pathways
Apoptosis: cell shrinks --> with budding/blebbing --> clean up by phagocytes
Necrosis --> cell swells --> with blebbing --> elicit inflammatory rxn
190
What are some apoptosis assays?
1) nuclear morphology: chromatin condensation and nuclear lobulation/fragmentation) in histo/EM
2) TUNEL and related assays
3) Caspase assays
4) Cyt C release into cytosol (want to see activated caspases)
191
How does a cell adapt to a "workload" imbalance?
1) atrophy when cells are no longer stimulated (can become necrotic)
2) hypertrophy/hyperplasia when cells are overstimulated
3) metaplasia: reversible, replacement of one adult cell types by another cell types of the same germ line (more to less specialized)
4) Dysplasia
5) Anaplasia
192
Define atrophy
focal or diffuse shrinkage of organ; reduction of cell size and number OR numeric atrophy with lipomatosis (loss of cells but replacement by adipocytes)
193
When does physiologic atrophy occur?
fetal development, thymus atrophy/atrophy of lymphoid tissue, senile atrophy (brown atrophy due to intracellular lipofuscin accumulation), age-independent atrophy (involution of uterus/mammary gland post partum)
194
What are pathologic atrophies?
1) localized = disuse atrophy, neurogenic atrophy, ischemic atrophy, compression/pressure atrophy, nerve cell atrophy
2) Generalized = inanition atrophy (starvation), systemic atrophy
195
Describe the mechanism of atrophy
increased protein degradation through:
1) lysosonal acid hydrolases
2) ubiquitin-proteasome pathway
- often accompanied by increased numbers of autophagic vacuoles
- if not digestible, membrane bound residual bodies remain
196
Define hypertrophy
response to increased stimulation of post-mitotic cell (permanent cells - neurons and cardiomyocytes)
197
Define hyperplasia
response to increased stimulation of cells with mitotic capacity (quiescent and labile)
198
What is metaplasia due to?
chronic damage
199
What are examples of metaplasia?
1) chronic irritation/inflammation = squamous metaplasia of respiratory epith
2) Vit A deficiency = squamous metaplasia of respiratory epith and glandular epith in psittacine birds
3) Hyperestrogenism = prostatic squamous metaplasia in ferret with adrenal tumor/ in dogs with testicular sertoli cell tumor
200
What are intracellular accumulations?
evidence of chronic sublethal cell injury and cellular adaptation
201
What are different types of intracellular accumulations?
1) accumulation of normal cellular comp due to increased production or decreased disposal
2) accumulation of abnormal cellular cop due to production of abnormal mols (endo) or due to up-take of cmpds (exo)
3) Accumulation of pigment
202
Describe characteristics of intracellular accumulations?
1) increase of cell size if severe enough
2) usually harmless to cell but occasional toxic
3) intracytoplasmic or intranuclear
4) may be reversible or permanent
203
What are causes of intracellular accumulations?
1) too much of a normal cell comp (lipid accumulation)
2) genetic or acquired defect of metabolism resulting in prod of non-functional enzymes (storage disease)
3) inability to degrade phagocytized material
204
What are intracellular lipid accumulations due to?
deranged intracellular fat metabolism
| -TAGs, cholesterol esthers, phospholipids
205
Where does intracellular lipid accumulations occur?
in hepatocytes and cardiomyocytes, myocytes and renal tubular epith cells
206
What is hepatocellular degeneration?
fatty liver, hepatic steatosis or lipidosis
207
What are the stages of hepatocellular degeneration?
1) early stages = FAs accumulate in small globules in cytoplasm of hepatocytes; cell have sharply delineated round clear cytoplasmic vacuoles
2) severe or long-standing=globules fuse --> large globule, uniformly light yellow, greasy and friable, floats in water or fixative
208
What is the pathogenesis of hepatocellular lipidosis?
excessive transport of FAs and carbs to liver; abnormal hepatocyte fn, decreased apoprotein/lipoproteins synthesis, impaired secretion of lipoproteins from the liver
209
What does deranged intracellular carb metabolism result in?
intracellular glycogen accumulation --> patho accumulation when glu and gly met is impaired, liver swollen and pale brown in severe cases; histo - cell cytoplasm has irregular clear spaces with indistinct outlines, nucleus central
210
What is characteristic of deranged intracellular protein metabolism?
1) hyaline cartilage - eosinophilic to glassy appearance
2) excessive production of normal protein
3) storage of abnormal proteins (degraded in proteosomes --> accumulate in cells)
4) resorption droplets in renal tubular epith cells (PT - inc urine protein conc --> inc resorption of protein)
211
what are other intracellular accumulations?
autophagic vacuoles, viral inclusion bodies, lead inclusions
212
define autophagocytosis
catabolic mechanism that involves cell degradation of unnecessary or dysfunctional cellular components via lysosomes
213
What mechanisms are involved in autophagocytosis?
1) vacuoles/phagolysosomes may be expelled from the cell or may be accumulate within cells in residual bodies containing lipofuscin
2) damaged/misfolded proteins are constantly marked by ubiquitin for disposal in proteasomes
214
What are extracellular accumulations?
hyaline substances, fibrinoid change, gout and pseudogout, cholesterol and collagen
215
What is gout?
deposition of urates as a result of oversaturation/overfeeding
-uric acids in blood in form of monosodium urate (rel insol in water)
216
How is gout formed?
increased concentration in blood or in synovial fluid or pH changes in fluids --> crystallization and formation of insoluble urate salts
217
Define primary and secondary gout
```
primary = excessive protein intake
secondary = decreased nitrogen excretion (renal disease and dehydration)
```
218
What are the two types of calcification?
dystrophic and metastatic
219
What is dystrophic calcification?
calcification in necrotic tissue (Ca accumulates in mito and cytoplasm); focal to multifocal lesion, normal serum Ca levels, rapid process in cardiomyocytes and muscle cells, bacterial and parasite granulomas; HARMLESS
220
What is metastatic calcification?
generalized intracellular or extracellular Ca salt deposits in previously undamaged tissue (mito); particular at elastic fibers and basement membranes and in cells iwth acidic cytoplasm (lungs); hypercalcemia; hyperparathyroidism
221
What are the different types of hyperparathyroidism?
1) primary = dysfunction
2) secondary renal = retain P, but body wants to maintian P:Ca ratio (PTH activated --> chief cell hyperplasia --> Ca from bones --> become soft --> Ca precipitate in blood
3) secondary nutritional
- mobilize Ca from bone --> hypercalcemia (due to chief cell hyperplasia)
222
What are the two main differences btw dystrophic and metastatic calcification?
dystrophic - necrotic tissue, normocalcemic
| metastatic - begins in healthy tissue, hypercalcemic (deposited in tissues)
223
What are the two pigment types?
exogenous and endogenous pigments
224
What are some exogenous pigments?
```
carbon - usually inhaled --> lung and lung lymph nodes (smoker or living with smoker); particles bronchiolar/alveolar macrophages
dust
tattoos
carotenoids
tetracyclins
melanin --> melanosis
lipfuscin-ceroid --> contain lipids/proteins
hematogenous pigments
```
225
What are carotenoids?
fat-sol pigments of plant origin includign precursors of vit A (b-carotene);
-not detectable in standard histo (washed out)
226
what are tetracyclins?
treatment of pregnant/gravid mother or neonatal animal --> discoloration of bones and teeth of neonate
227
Give examples of hematogenous pigments
hemoglobin, hematin, hemosiderin, hematoidin, bilirubin, porphyrin
228
Describe melanin
black intracellular pigment, produced by melanoblasts/melanocytes
- -> hyperpigmentationn of skin, focal - freckles and moles
- Depigmentation - destruction of melanocytes with release of melanin --> phagocytized and removed; generalized (Cu def); albinism
229
What is albinism
inherited defect of enzyme system for melanin production
230
What is lipofuscin?
yellow brown intracellular pgiment; contains proteins and lipids;
231
What is the morphology of lipofuscin?
- autofluorescent
- may cause brownish discoloration of tissues (brown atrophy)
- accumulates to the degree of visibility at LM (post mitotic cells-neurons and slowly dividing cells-hepatocytes)
- non-degradable end prdt of autophagocytosis of damaged organelles
- usually harmless to cell (unless storage disease)
232
What is hemoglobin?
- red pigment
- degradation in macrophages of liver, spleen and bone marrow
- broken down to heme and globin --> bile acids and iron bind to proteins
- acute severe hemolysis leads to hemoglobinemia and hemoglobinuria
233
Describe hemosiderin
brown pigment
- reserve iron: bound to protein, either ferritin or siderin (non-bioavailable iron)
- siderin is stored in siderosomes (granules)
234
What is generalized hemosiderosis?
usually due to hemolysis, first detectable in macrophages (bone marrow, spleen, liver)
235
What is localized hemosiderosis?
in areas of hemorrhages including in body cavity after intracavitary hemorrhage
236
What is hemochromatosis?
increased enteric iron resorption with massive storage in hepatocytes
237
What is parasite hematin?
waste product of certain parasites
238
What is acid hematin?
melena (blood exposed to HCl in stomach)
239
What is a formalin pigment?
annoying microscopic formalin artifact when pH of fixative < 6
-artifact of processing
240
What is hematoidin?
produced from hemoglobin in tissue after hemorrhage
- detectable 9 days after
- free of iron
- birefringement
- resembles bilirubin
241
What is hyperbilirubinemia a result of?
hemolysis
242
What are the 3 different types of icterus?
1) prehepatic = hemolysis
2) hepatic = damage of hepatocytes or biliary cells --> impaired uptake , metabolism, secretion and transport of bile pigments within the liver
3) posthepatic = extrahepatic cholestasis (main bile duct)
- bilirubin stains tissue yellowish --> adipose, sclera, arteries, tendons
243
Can you see bilirubin in tissues?
no, only in liver
| -don't confuse with carotenoid pigments or localized hemosiderosis
244
What is bilirubin?
end product of hemoglobin metabolism during RBC degradation in cells of mononuclear macrophage system
245
What is hemoglobin?
heme, iron and globin --> bilirubin --> glucoronide --> bile canaliculi --> urobilinogen --> excretion in feces
246
What are types of disturbances of keratosis/cornification?
1) hyperkeratosis - regular but excessive cornification (skin callus)
2) parakeratosis - faulty maturation of the stratum corneum (greasy skin, Zn def)
247
What are concretions?
precipitation of organic material and Ca salts or other minerals
- pathogenesis involves an increased conc of water insoluble cmpds and a crystallization point
- occurs mainly in alimentary tract and urinary tract
248
Give examples of concretions
```
salivary gland - sialoliths
biliary system of liver - choleliths
pancreas - pancreatic calculi
teeth - tartar, dental calculus
urinary tract - sediment or calculi
```
249
What are pseudoconcretions?
stony conglomerations of inspissated exudates (calculi in guttural pouches of horses, calculi in vagina, preputial calculi)
-trichobezoars in GI tract or plant material
