CH1 - Growth Adaptations, Cellular Injury, and Cell Death Flashcards
1
Q
What are the basic principles of growth adapdations?
A
An organ is in homeostasis with the physiologic stress placed on it. An increase, decrease, or change in stress on an organ can result in growth adaptations.
2
Q
What leads to an increase in organ size?
A
An increase in stress
3
Q
Hypertrophy occurs via what?
A
an increase in the size
4
Q
Hyperplasia occurs via what?
A
an increase in the number of cells
5
Q
What does hypertrophy involve?
A
gene activation, protein synthesis, and production of organelles.
6
Q
What does Hyperplasia involve?
A
the production of new cells from stem cells.
7
Q
Permanent tissues are… Do they undergo hypertrophy or hyperplasia?
A
cardiac muscle, skeletal muscle, and nerve, cannot make new cells and undergo hypertrophy only.
8
Q
Pathologic hyperplasia leads to what?
A
(e.g., endometrial hyperplasia) can progress to dysplasia and,eventually cancer.
9
Q
What is an exception to pathologic hyperplasia leading to cancer?
A
benign prostatic hyperplasia (BPH), which does notincrease the risk for prostate cancer,
10
Q
What leads to a decrease in organ size?
A
A decrease in stress (e.g., decreased hormonal stimulation, disuse, or decreased nutrients/blood supply) (atrophy).
11
Q
Atrophy occurs via?
A
a decrease in the size and number of cells
12
Q
How does a decrease in cell number occur?
A
via apoptosis.
13
Q
Decrease in cell size occurs via what?
A
ubiquitin-proteosome degradation of the cytoskeleton and autophagy of cellular components.
14
Q
What happens in ubiquitin-proteosome degradation?
A
intermediate filaments of the cytoskeleton are tagged with ubiquitin and destroyed by proteosomes.
15
Q
What does autophagy of cellular components involve?
A
generation of autophagic vacuoles that fuse with lysosomes whose hydrolytic enzymes breakdown cellular components.
16
Q
What happens in METAPLASIA?
A
change in stress on an organ leads to a change in cell type
17
Q
Metaplasia most commonly involves?
A
change of one type of surface epithelium (squamous, columnar, or urothelial) to another
18
Q
How do metaplastic cells handle the new stress?
A
they are better able to handle the new stress.
19
Q
Esophagus is normally lined by what?
A
nonkeratinizing squamous epithelium (suited to handle friction of a food bolus)
20
Q
Barrett esophagus
A
Acid reflux from the stomach causes metaplasia to nonciliated mucin-producing columnar cells (better able to handle the stress of acid
21
Q
Metaplasia occurs via what?
A
programming of stem cells, which then produce the new cell type.
22
Q
Is Metaplasia reversible?
A
with removal of the driving stressor.
23
Q
Can metaplasia progress to cancer?
A
Under persistent stress, can progress to dysplasia and eventually result in cancer.
24
Q
What is an exception to metaplasia leading to cancer?
A
apocrine metaplasia of breast with benign epithelial alteration of breast tissue, which means that epithelial cells are undergoing an unexpected change.
(apocrine means related to sweat glands, but this is only a resemblance. It’s not actually sweat gland related), which carries no increased risk for cancer.
25
Vitamin A deficiency can result in what?
metaplasia,
26
Vitamin A is necessary for what?
differentiation of specialized epithelial surfaces such as the conjunctiva covering the eye.
conjunctiva - the mucous membrane that covers the front of the eye and lines the inside of the eyelids, composed of non-keratinized, stratified squamous epithelium with goblet cells, and also stratified columnar epithelium. The conjunctiva is highly vascularised, with many microvessels. Conjunct- latin origin for join together = eye lid and eye ball
27
Keratomalacia
In vitamin A deficiency, the thin squamous lining of the conjunctiva undergoes metaplasia into stratified keratinizing squamous epithelium.
28
Myositis Ossificans
Mesenchymal (connective) tissues can undergo metaplasia. A classic example is myositis ossificans in which muscle tissue changes to bone during healing after trauma
29
DYSPLASIA is?
Disordered cellular growth
30
Dysplasia most often refers to?
proliferation of precancerous cells
31
Cervical intraepithelial neoplasia (CIN)
represents dysplasia and is a precursor to cervical cancer
32
Dysplasia often arises from?
longstanding pathologic hyperplasia (e.g., endometrial hyperplasia) or metaplasia (e.g., Barrett esophagus)
33
Is dysplasia is reversible?
yes, with alleviation of inciting stress.
34
In dysplasia what happens if stress persists?
dysplasia progresses to carcinoma irreversible)
35
What is aplasia?
it is failure of cell production during embryogenesis (e.g., unilateral renal agenesis)
36
What is hypoplasia?
it is a decrease in cell production during embryogenesis, resulting in a relatively small organ (e.g., streak ovary in Turner syndrome)
37
When does cellular injury occur?
when a stress exceeds the cells ability to adapt
38
The likelihood of injury depends on what?
the type of stress, its severity, and the type of cell affected.
39
What are highly susceptible to ischemic injury? As opposed to?
neurons whereas, skeletal muscle is relatively more resistant.
40
Slowly developing ischemia
eg: renal artery atherosclerosis, results in ATROPHY
41
acute ischemia
eg: renal artery embolus, results in INJURY
42
What are common causes of cellular injury?
inflammation, nutritional deficiency or excess, hypoxia, trauma, and genetic mutations.
43
What is HYPOXIA?
Low oxygen delivery to tissue; important cause of cellular injury
44
What is the final electron acceptor in the electron transport chain of oxidative phosphorylation?
Oxygen
45
Decreased oxygen results in what?
impairs oxidative phosphorylation, resulting in decreased ATP production
46
What does a lack of ATP leads to?
cellular injury
47
What are some causes of hypoxia?
include ischemia, hypoxemia, and decreased 02 - carrying capacity of blood = anemia
48
Ischemia is?
decreased blood flow through an organ
49
Ischemia arises with?
1. Decreased arterial perfusion (eg atherosclerosis) 2. Decreased venous drainage (eg Budd-Chiari syndrome) 3. Shock?generalized hypotension resulting in poor tissue perfusion
50
Hypoxemia is?
a low partial pressure of oxygen in the blood (Pao2\< 60 mm Hg, SaO2\<90%).
51
Hypoxemia arises with
1. High altitude 2. Hypoventilation 3. Diffusion defect 4. V/Q mismatch
52
High altitude to hypoxemia, how?
Decreased barometric pressure results in decreased PaO2
53
Hypoventilation to hypoxemia, how?
Increased Paco, results in decreased PaO2
54
Diffusion defect to hypoxemia, how?
PAO2 not able to push as much O2 into the blood due to a thicker diffusion barrier (e.g., interstitial pulmonary fibrosis)
Latin interstitium "interval," literally "space between," from inter "between" + stare "to stand,"
55
V/Q mismatch to hypoxemia, how?
Blood bypasses oxygenated lung (circulation problem, eg: right-to-left shunt), or oxygenated air cannot reach blood (ventilation problem, eg: atelectasis)
Atelectasis is the collapse of part or, much less commonly, all of a lung
Greek atelēs ‘imperfect’ + ektasis ‘extension.’
56
Decreased O2-carrying capacity arises with what?
hemoglobin (Hb) loss or dysfunction
57
What are some examples of Decreased O2-carrying capacity?
1. Anemia 2. Carbon monoxide poisoning 3. Methemoglobinemia
Methemoglobinemia is a condition caused by elevated levels of methemoglobin in the blood. Methemoglobin is a form of hemoglobin that contains the ferric [Fe3+] form of iron. The affinity for oxygen of ferric iron is impaired.
58
Anemia leading to decreased O2 carrying capacity.
(decrease in RBC mass) PaO2 normal; SaO2 normal
59
Carbon monoxide poisoning
CO binds hemoglobin more avidly than oxygen
60
What is the PaO2 and SaO2 for carbon monoxide poisoning?
PaO2 normal; SaO2 decreased
61
Exposures for Carbon monoxide poisoning
include smoke from fires and exhaust from cars or gas heaters.
62
Classic finding for Carbon monoxide poisoning
cherry-red appearance of skin.
63
Early sign of exposure for Carbon monoxide poisoning
headache; significant exposure leads to coma and death.
64
What is Methemoglobinemia?
Iron in heme is oxidized to Fe3+ which cannot bind oxygen
65
PaO2 and SaO2 for Methemoglobinemia?
PaO2 normal; SaO2 decreased
66
Methemoglobinemia is Seen with?
oxidant stress (eg sulfa and nitrate drugs) or in newborns
67
Classic finding for Methemoglobinemia?
cyanosis with chocolate-colored blood.
68
Treatment for Methemoglobinemia?
intravenous methylene blue, which helps reduce Fe3+ back to Fe2+ state.
69
Hypoxia results in low ATP how?
impairs oxidative phosphorylation resulting in decreased ATP.
70
Low ATP disrupts what?
key cellular functions including 1. Na/K pump 2. Ca2+ pump 3. Aerobic glycolysis
71
Disruption of Na/K pump results in what?
sodium and water buildup in the cell
72
Disruption of Ca2+ pump results in what?
Ca2+ buildup in the cytosol of the cell
73
Disruption of Aerobic glycolysis results in what?
switch to anaerobic glycolysis. Lactic acid buildup results in low pH, which denatures proteins and precipitates DMA.
74
The hallmark of reversible injury is
cellular swelling.
75
Cytosol swelling results in
loss or microvilli and membrane blebbing.
76
Swelling of the rough endoplasmic reticulum (RER) results in
dissociation of ribosomes and decreased protein synthesis.
77
The hallmark of irreversible injury is
membrane damage.
78
Plasma membrane damage results in
1. Cytosolic enzymes leaking into the serum {e.g cardiac troponin) 2. Additional calcium entering into the cell
79
Mitochondrial membrane damage results in
1. Loss of the electron transport chain (inner mitochondrial membrane) 2. Cytochrome c leaking into cytosol (activates apoptosis)
80
Lysosome membrane damage results in
hydrolytic enzymes leaking into the cytosol, which in turn, are activated by the high intracellular calcium.
81
The end result of irreversible injury is
cell death.
82
The morphologic hallmark of cell death is
loss of the nucleus,
83
loss of the nucleus occurs via
nuclear condensation (pyknosis), fragmentation (karyorrhexis), and dissolution (karyolysis = nuclear fragments broken down into building blocks)
greek = puknós, “compact”
karyo- greek kernel
Greek rexis- breaking, bursting
Greek lusis ‘loosening,’
84
The two mechanisms of cell death are
necrosis and apoptosis.
85
NECROSIS
A. Death of large groups of cells f**ollowed by acute inflammatio**n B. Due to some underlying pathologic process; never physiologic C. Divided into several types based on gross features
86
GROSS PATTERNS OF NECROSIS
1. Coagulative necrosis, 2. liquefactive necrosis, 3. Gangrenous necrosis 4. Caseous necrosis 5. Fat necrosis 6. Fibrinoid necrosis
87
What is Coagulative necrosis?
Necrotic tissue that remains **firm**, cell s**hape and organ structure are preserved** by coagulation of proteins, but the nucleus disappears
**cell structure remains but** **nucleus** **is gone**
coagulation - changing into solid or semi-solid state
Usually NOT CAUSED by severe trauma, toxins or an acute or chronic immune response. As a result protein cytoskeleton is not digested by proteolytic enzymes.
Latin coagulat- ‘curdled,
88
Coagulative necrosis is Characteristic of?
ischemic infarction of any organ except the brain
89
Area of infarcted tissue for Coagulative necrosis?
It is often wedge-shaped (pointing to focus of vascular occlusion) and pale (because won't enter tissue).
90
What is Red infarction
arises if blood re-enters a loosely organized (so it can hold blood) tissue (e.g. pulmonary or testicular infarction)
when testicular torsion occurs, the thick walled artery still allows blood to enter testicle, but thin walled vein collapses. The result is blood enters but can not leave.
Fresh blood can not enter because blood piles up.
91
What is Liquefactive necrosis?
Necrotic tissue that becomes **liquefied because of hydrolytic enzymes - usually from immune cells**;
enzymatic lysis of cells and protein results in liquefaction.
92
Liquefactive necrosis is Characteristic of?
Brain infarction, abscess, pancreatitis
93
What type of necrosis for brain infarction?
Liquefactive necrosis - Proteolytic enzymes from microglial cells liquefy the brain using hydrolytic enzymes.
94
What type of necrosis for abscess?
Liquefactive necrosis - hydrolytic enzymes from neutrophils liquefy tissue
95
What type of necrosis for pancreatitis?
Liquefactive necrosis - Proteolytic enzymes from pancreas liquefy parenchyma. auto-digestion
96
What is Gangrenous necrosis?
Coagulative necrosis that resembles mummified tissue (dry gangrene) - often lower extremeties of popliteal artery partially obstructed -\> ischemia of lower limb.
seen in diabetics
"looks like gangrene"
gran- "to gnaw," gras- "to devour
97
Gangrenous necrosis is characteristic of?
ischemia of lower limb and GI tract
98
What is wet gangrene?
superimposed infection of dead tissues occurs, then liquefactive necrosis ensues (wet gangrene).
Infection -\> acute inflmmation-\> PMN's -\> hydrolytic enzymes -\> liquefactive necrosis.
99
What is Caseous necrosis?
Soft and friable necrotic tissue with cottage cheese-like appearance. It's liquefactive necrosis, that is thickened into a "coagulative-like" gel due to thinkening agents (wall of fungus ro TB)
100
What is caseous necrosis characteristic of?
granulomatous inflammation due to tuberculous or fungal infection
101
What is fat necrosis?
Necrotic adipose tissue with chalky-white appearance due to deposition of calcium on fat released from necrotic acdipocytes
102
What is fat necrosis characteristic of?
trauma to fat (eg. breast) and pancreatitis-mediated damage of peripancreatic fat
103
Fat necrosis and saponification
Fatty acids released by trauma (eg to breast) or lipase (eg pancreatitis) join with calcium via a process called saponification which is an example of dystrophic calcification in which calcium deposits on dead tissues.
sapon- "soap" (see soap (n.)) + -ficare - to make
dystrophic - dys - bad, trophic- nourishment
104
dystrophic calcification
the necrotic tissue acts as a nidus for calcification in the setting of normal serum calcium and phosphate e.g. saponification = dead fat reacts with Calcium
**Dystrophic calcification** with saponification seen also in tumors that outgrow their blood supply causing neoplastic cells in tumor core to necrose and be saponified with calcium.
**_Examples_**
1) psammoma bodies in papillary carcinoma of the thyroid
2) meningiomas
3) papillary serious carcinoma of the ovary
105
Dystrophic calcification vs metastatic calcification
high serum calcium or phosphate levels lead to calcium deposition in normal tissues throughout the body (eg. hyperparathyroidism leading to nephrocalcinosis)
106
Fibrinoid necrosis
**Necrotic damage to blood vessel wall endothelial cells**, Leaking of proteins (including fibrin) into vessel wall results in bright pink staining of the wall microscopically
107
What is fibrinoid necrosis characteristic of?
malignant hypertension and vasculitis
**_malignant hypertension -\> can be seen in preeclampsia -\> fibrinoid necrosis of placenta_**
1) headache
2) renal failure
3) papilledema - condition in which increased pressure in or around the brain causes the part of the optic nerve inside the eye to swell.
108
What is apoptosis?
Energy (ATP)-dependent, genetically programmed cell death involving single cells or small groups of cells.
109
Examples of apoptosis include
1. Endometrial shedding during menstrual cycle 2. Removal of cells during embryogenesis 3. CD8+ T cell-mediated killing of virally infected cells
110
Morphology of apoptosis
1. Dying cell shrinks, leading cytoplasm to become more eosinophilic (pink -\> because cytoplasm becomes concentrated in cell as cell shrinks) 2. Nucleus condenses (pyknosis) and fragments (karyorrhexis).
puknós, “compact”
[karyo- kernel + G. rhexis, rupture]
111
Apoptotic bodies
fall from the cell and are removed by macrophages; apoptosis is not followed by inflammation
112
Apoptosis is mediated by
**caspases**
1) activate proteases (trash cytoskeleton)
2) endonucleases (an enzyme that cleaves DNA by separating nucleotides)
due to
1) ) cellular injury
2) DNA damage
3) decreased hormonal activation of bcl2
113
Proteases
break down the cytoskeleton.
114
Endonucleases
break down DNA,
115
How are caspases activated?
1. Intrinsic mitochondrial pathway 2. Extrinsic receptor-ligand pathway 3. Cytotoxic CD8+ Tcell-mediated pathway
116
What is the main molecule in the intrinsic mitochondrial pathway?
Cytochrome C
Bcl2 stabilizes Cyt C in Mitochondria
when Bcl2 get inactivated by (membrane damage, DNA damage, or decreased hormonal stimulation) CytC can leak out of mitochondria ancaspasese caspapses.
117
What happens to Bcl2 in the intrinsic mitochondrial pathway?
Cellular injury, DNA damage, or loss of hormonal stimulation leads to inactivation of Bcl2
118
In the intrinsic mitochondrial pathway lack of Bcl 2 results in what?
allows cytochrome c to leak from the inner mitochondrial matrix into the cytoplasm and activate caspases.
119
What is the extrinsic receptor-ligand pathway?
FAS ligand binds to (CD95) FAS death receptor and TNF binds TNF receptor (both activate caspases)
Tcells leave BM and go to thymus for education
1) positive selection -\> can you bing self-antigen + MHC
2) Negative selection -\> do you bind self-antigen too strongly -\> if they do, TCell is destroyed because bound cell ex[resses FAS ligand which binds to death receptor on Tcell
120
What is an example of FAS ligand binding to FAS death receptor (CD95) on the target cell activating caspases
negative selection of thymocytes in thymus
121
Cytotoxic CD8+ T cell-mediated pathway releases what?
perforins and granzyme ex CD8+ T-cell killing of virally infected cells is an example.
Perforin is a pore forming cytolytic protein found in the granules of cytotoxic T lymphocytes
Granzymes are serine proteases that are released by cytoplasmic granules within cytotoxic T cells and natural killer (NK) cells. They induce apoptosis in cancerous or virally infected cells
122
Perforins
secreted by CD8+ T cell create pores in membrane of target cell
123
Granzyme
secreted from CD8+ T cell enters pores and activates caspases
124
Free radicals are what?
chemical species with an unpaired electron in their outer orbit.
125
When does physiologic generation of free radicals occur?
it occurs during oxidative phosphorylation
oxygen accepts 4 electrons to make water. If oxygen does not accept all 4 electrons, free radicals are generated "physiologically"
126
How are free radicals generated physiologically?
Cytochrome c oxidase (complex IV) transfers electrons to oxygen. Partial reduction of O2 + e' -\> superoxide (O2.-) + e'
- \>hydrogen peroxide (H202)+ e' -\>hydroxyl radicals (OH.-) + e'
- \> H2O (water)
127
Pathologic generation of free radicals arises with?
Ionizing radiation, inflammation, metals, drugs and chemicals
128
Ionizing radiation and Pathologic generation of free radicals
water hydrolyzed to hydroxyl free radical OH.-
Hydroxyl Free Radical is **MOST DAMAGING**
129
Inflammation and Pathologic generation of free radicals
PMN's kill microbe via 1) oxygen dependent 2) oxygen INDEPENDENT mechanisms
1) oxygen dependent = **Oxidative Burst**
**NADPH oxidase** generates superoxide (O·̄2) ions from O2
during oxygen dependent killing by neutrophils.
Superoxide dismutase will convert SUPEROXIDE -\> Hydrogen Peroxide
Myeolperoxidase will convert Hydrogen Peroxide to HOCl (Bleach)
Hypochlorous acid (HClO) is a weak acid that forms when chlorine dissolves in water, and itself partially dissociates, forming ClO-. HClO and ClO- are oxidizers, and the primary disinfection agents of chlorine solutions
130
Metals and Pathologic generation of free radicals
(e.g., copper and iron) Fe generates hydroxyl free radicals (Fenton reaction).
hydroxyl free radicals are the most dangerous free radical
IN diseases where Fe builds up, e.g. Hemochromatosis -\> cirrhosis in liver and tissue damage throughout the body is mediated through excess Fe generated hydroxyl free radicals **(Fenton reaction)**.
Wilson's disease- excess of Cu -\> Generates free radicals -\> tissue damage
131
Drugs and chemicals and Pathologic generation of free radicals
P450 system of liver metabolizes drugs (e.g acetaminophen), generating free radicals.
132
Free radicals cause
cellular injury via
1) peroxidation of lipids -\> damage cells
2) oxidation of DNA and proteins, damage cells -\> oncogenesis b/c damage DNA -\> mutation, aging
DNA damage is implicated in aging and oncogenesis.
133
Elimination of free radicals occurs via what?
1) Antioxidants -
2) Enzymes
3) Metal carrier proteins e.g. transferrin in blood or ferritin in liver and Mphage. They hide away metal so that free radicals not generated
134
Elimination of free radicals via Antioxidants
glutathione and vitamins A , C, and E
135
Elimination of free radicals via Enzymes
SOD (takes Superoxide radical -\> H2O2 )
catalase (H2O2 -\> Hydroxyl radical)
glutathione peroxidase (Hydroxyl radical to water) using glutathione antioxidant for part of the reaction
136
Superoxide dismutase
(in mitochondria) superoxide (O2.- -\>H202)
137
Glutathione peroxidase
(in mitochondria) GSH + free radical GSSH and H202
138
Catalase
(in peroxisomes) H2O2 ?\> O2 and H202
peroxisomes- organelles involved in catabolism of very long chain fatty acids, branched chain fatty acids, D-amino acids, and polyamines, reduction of reactive oxygen species – specifically hydrogen peroxide
139
Elimination of free radicals via Metal carrier proteins
transferrin and ceruloplasmin (keep Fe and Cu sequestered while traveling in blood)
140
Free Radical Injury
Carbon tetrachloride (CCl4) and Reperfusion Injury
141
Carbon tetrachloride - What is it used for?
Organic solvent used in the dry cleaning industry
142
How is CCl4 metabolized?
Converted to CCl3'-(Carbon trichloride) free radicals by P450 system of hepatocytes -\> damages membrane of Hepatocytes
Step 1 ) reversible (cell swelling), Rough ER swells, Ribosomes pop off -\> Protein synthesis ↓
Protein synthesis ↓ -\> Apolipoproteins can not bind up cholesterol and lipids and take it out of liver to other sites via blood -\> FATTY CHANGE OF THE LIVER (because fat is accumulating in liver)
143
CCl4 results in what?
cell injury with swelling of RER, ribosomes detach, impairing protein synthesis. Decreased apolipoproteins lead to fatty change in the liver
Apolipoproteins are proteins that bind lipids (oil-soluble substances such as fat and cholesterol) to form lipoproteins. They transport the lipids through the lymphatic and circulatory systems. The lipid components of lipoproteins are insoluble in water.
144
Reperfusion injury
Return of blood to ischemic tissue results in production of O2-derived free radicals, which further damage tissue. Leads to a continued rise in cardiac enzymes (troponin) after reperfusion of infarcted myocardial tissue
Return of blood brings inflammatory cells to necrotic tissue _ fresh O2 coming in -\> Free radical generation -\> further damage to an even larger area of surrounding cardiac myocytes -\> Increased cardiac enzymes in blood after reperfusion of the blocked artery
145
What is an amyloid?
It is a misfolded protein that deposits in the extracellular space (OUTSIDE THE CELL), thereby damaging tissues.
146
What are the shared features of amyloid proteins?
1) beta-pleated sheet configuration
2) Congo red staining
3) apple-green birefringence when viewed microscopically under polarized light
4) Deposition can be systemic or localized
5) Deposition often around blood vessels in Extracellular space
systemic amyloidosis can be split into Primary and secondary types
147
What is primary amyloidosis?
It is systemic deposition of AL amyloid, which is derived from immunoglobulin light chain
AL amyloid deposit in various tissues around the body = primary amyloidosis
148
What is primary amyloidosis associated with?
plasma cell dyscrasias (e.g multiple myeloma) = abnormalities of the plasma cell -\> overproduction of light chain relative to heavy chain -\> leaks out into blood -\> becomes misfolded -\> deposits in ECS of tissues
dyscrasia - abnormal or disordered state of the body or of a bodily part
dus- ‘bad’ + krasis ‘mixture.’
149
Secondary amyloidosis is?
systemic deposition of AA amyloid, which is derived from serum amyloid-associated protein (SAA = acute phase reactant).
Therefore, Secondary amyloidosis is the product of chronic inflammation
150
What is SAA?
It is an acute phase reactant that is increased in chronic inflammatory states, malignancy, and Familial Mediterranean Fever (FMF).
inflammatory states e.g.
1) autoimmune disease
2) rheumatoid arthritis
3) chronic osteomyelitis - long progressive infection in bone marrow
4) Cancer can cause a low grade chronic inflammatory state as a reaction to tumros
SAA-\> AA-\> deposits
151
What is FMF due to?
a dysfunction of neutrophils (autosomal recessive) and occurs in persons of Mediterranean origin.
Dysfunctioning neutrophils can create attack of acute inflammation NOT in response to infection -\> fever, and causes inflammatsurfacessal surfases -\> classic findings
heart serosa affected -\> pericardium -\> can mimic Myoc Infarc
Abdomen serosa -\> mimics acute appendicitis
Acute serosal inflammation, and inflammation in general -\> production of acute phase reactants by liver (SAA) -\> gets released into blood where misfolds and deposits in tissues Extracellular space as AA
152
What does FMF present with?
episodes of fever and acute serosal inflammation
153
FMF can mimic what?
appendicitis, arthritis, or myocardial infarction
154
How does FMF result in AA amyloid deposition in tissues?
High SAA during attacks deposits as AA amyloid in tissues
155
What is the most common organ involved in systemic amyloidosis?
kidney (usually nephrotic syndrome = \<3.5 g/day of protein loss in urine)
156
What are the clinical findings of systemic amyloidosis?
Nephrotic syndrome
Restrictive cardiomyopathy or arrhythmia - heart can't fill properly because walls become less compliant
Tongue enlargement
malabsorption due to thickening of the wall of bowel
hepatosplenomegaly
157
Diagnosis of systemic amyloidosis requires what?
tissue biopsy, Abdominal fat pad and rectum are easily accessible biopsy targets.
158
Damaged organs of systemic amyloidosis must be...
transplanted. Amyloid cannot be removed.
159
What is localized amyloidosis?
Amyloid deposition that is usually localized to a single organ
160
What is senile cardiac amyloidosis?
**Non-mutated** serum transthyretin (second to albumin most common protein in blood) deposits in the heart slowly over lifetime.
Usually **asymptomatic**; present in 25% of individuals \> 80 years of age
Transthyretin (TTR) is a transport protein in the serum and cerebrospinal fluid that carries the thyroid hormone thyroxine (T4)
senile - having or showing the weaknesses or diseases of old age
Latin senilis, from senex ‘old man.’
161
Familial amyloid cardiomyopathy
**Mutated** serum transthyretin deposits in the heart leading to **restrictive cardiomyopathy -\> can't pump properly -\> eventually cardiac failure**, 5% of African Americans carry the mutated gene.
IS NOT asymptomatic like NON-MUtated form
162
Non-insulin-dependent diabetes mellitus (type II -\> reistance to insulin at the level of skeletal muscle and adipose tissue)
Initially body fights insulin insensitivity by overproducing insulin. Amylin (derived from insulin) deposits in the islets of the pancreas
co-secreted with insulin from the pancreatic β-cells in the ratio of approximately 100:1. Amylin plays a role in glycemic regulation by slowing gastric emptying and promoting satiety, thereby preventing post-prandial spikes in blood glucose levels.
163
Alzheimer disease
amyloid beta (derived from J-amyloid precursor protein) deposits in the brain forming amyloid plaques
164
Gene for J-APP is present on...
chromosome 21.
165
Downs syndrome and Alzheimers?
Most individuals with Down syndrome (trisomy 21) develop Alzheimer disease by the age of 40 (early-onset).
166
Dialysis-associated amyloidosis
β₂ microglobulin-deposits in joints, because not filtered well via dialysis
β₂ microglobulin also known as B2M is a component of MHC class I molecules, which are present on all nucleated cells. It stabilizes MHC class I
167
Medullary carcinoma of the thyroid
Calcitonin (produced by tumor cells) deposits within the tumor ('tumor cells in an amyloid background').
Calcitonin - made by parafollicular cells C-cells of the thyroid. Acts to reduce blood calcium (Ca2+), opposing effects of PTH
168
Why can't permanent tissues make new cells?
Because they do not have stem cells.
169
Fibrocystic breast disease
noncancerous breast lumps. sometimes cause discomfort periodically related to hormones of menstrual cycle. affects 30-60% of women lifetime prevalence of FBC may be as high as 70% to 90%.
170
Apocrine metaplasia
reversible transformation of cells to an apocrine phenotype.
Apocrine - exocrine gland cells that Cells bud their secretions off by producing membrane-bound vesicles in the lumen.
female \>50.y.o. Metaplasia happens when there is an irritation to the breast (breast cyst).
apo- away + Greek krinein ‘to separate.’
171
KERATOMALACIA
Replacement of the normal NON-KERATINIZED SQUAMOUS EPITHELIUM OF conjunctivae by an inappropriate keratinized stratified squamous epithelium.
172
Is inflammation more likely to cause growth adaptation or injury?
adaptation
173
Fat necrosis
often seen in breast trauma
as a mass - giant cell immune reaction to the fat - \> calcification
NOT ductal carcinoma is situ which also has calcification
