Module 1 - Altered Cellular and Tissue Biology Flashcards
1
Q
Describe cellular adaptation
A
- This is when cells adapt to their environment to escape and protect themselves from injury
- An adapted cell is neither normal nor injured - condition lies between these 2 states
- It is reversible changes in size, number, phenotype, metabolic activity or functions of cells
2
Q
Give examples of adaptive changes in cells
A
- Atrophy - decrease in cells size
- Hypertrophy - increase in cell size
- Hyperplasia - increase in cell number
- Metaplasia - reversible replacement of one mature cell type by another less mature cell type or a change in the phenotype
3
Q
What is Dysplasia?
A
- This is deranged cellular growth, not a true adaptation
- It is atypical hyperplasia
4
Q
Atrophy
A
Decrease or shrinkage in cellular size
5
Q
Where is atrophy most common?
A
Skeletal muscle, heart, secondary sex organs, brain
6
Q
True or False: Atrophy can be physiological or pathological.
A
True
7
Q
True or False: Atrophy is only physiological.
A
False
8
Q
What does an atrophic muscle cell contains less of?
A
ER, mitochondria and myofilaments.
9
Q
What causes immediate reduction of O2 consumption and amino acid uptake in muscular atrophy
A
Nerve loss.
10
Q
What are the mechanisms of atrophy?
A
- Decreased protein synthesis
- Increased protein catabolism
- Ribosome biogenesis may also play a role
11
Q
What is the primary pathway of protein catabolism?
A
UPS - ubiquitin-proteasome pathway.
12
Q
An increase in proteasome activity is characteristic of what changes?
A
Atrophic muscle changes
13
Q
Deregulation of UPS leads to what?
A
Abnormal cell growth and is associated with cancer and other diseases.
14
Q
What accompanies atrophy due to chronic malnutrition?
A
It is accompanied by self eating process called autophagy that creates autophagic vacuoles.
15
Q
What are autophagic vacuoles?
A
- membrane bound vesicles within the cells
- it contains cellular debris and hydrolytic enzymes which function to breakdown substances to the simplest unit of fat, carbs, or protein.
16
Q
What happens to the levels of hydrolytic enzymes during atrophy?
A
It rises rapidly
17
Q
What do these autophagic vacuoles do?
A
This is where hydrolytic enzymes are isolated to prevent uncontrolled cellular destruction. This process protects uninjured organelles from injured organelles. Theyare eventually engulfed and destroyed by lysosomes.
18
Q
Give an example of granules that can persist and resist breakdown.
A
Examples are granules that contains lipofuscin - yellow brown pigment - usually accumulates in liver cells, myocardial cells, and atrophic cells.
19
Q
Give examples of Atrophy
A
- Physiological - occurs in early development e.g. thymus gland undergoes physiological atrophy during childhood.
- Pathological -
- decreases in workload, pressure, use, blood supply, nutrition, hormonal stimulation, and nervous system stimulation. e.g. individuals immobilized in bed for a prolonged period of time, aging causes brain cells to become atrophic, endocrine-dependent organs can shrink as hormonal stimulation decreases.
20
Q
Hypertrophy
A
-Compensatory increase in the size of the cell in response to mechanical stimuli (also mechanical load or stress).
-Examples are from repetitive stretching, chronic pressure or volume overload.
-This can lead to increases in size of organ.
21
Q
Which are the 2 organs most prone to hypertrophy/enlargement?
A
Heart and kidneys
22
Q
What is involved in cardiac hypertrophy?
A
It involves changes in signaling and transcription factor pathways which leads to increased protein synthesis - this leads to LVH.
23
Q
What remains intact with physical hypertrophy?
A
Myocardial structure and function despite increased workload of the heart.
24
Q
Give examples of physical hypertrophy.
A
- Normal growth and development
- moderate endurance exercise training
- pregnancy
- early phases of increased pressure and volume loading on the adult human heart
25
What is associated with pathological hypertrophy in the heart?
Structure and functional changes to the heart.
26
Pathological hypertrophy is secondary to what conditions/factors?
- HTN, coronary heart disease, problem valves.
- Aging, strenuous exercise, sustained workload, or stress
27
What is a key risk factor to heart failure?
Pathological hypertrophy
28
What are the results of the structural and functional manifestations of pathological hypertrophy?
- Interstitial fibrosis
- Cellular death
- Cardiac cardiac function
29
What is hyperplasia?
This is the increased number of cells resulting from an increased rate of cellular division.
30
When does hyperplasia occur as a response to injury?
It occurs when the injury has been severe and prolonged enough to have caused cellular death.
31
Hyperplasia and a. ___________ often occur together. Both take place if the cells can b.______________ DNA.
1. Hypertrophy
2. Synthesize
32
What are to types physiological hyperplasia?
1. Compensatory
2. Hormonal
33
Compensatory Hyperplasia
Adaptive mechanism that enables certain organs to regenerate
34
Give an example of Compensatory hyperplasia.
- Removal of part of the liver --> leads to hyperplasia of hepatocytes to compensate for the loss. Even removal of 70% of liver, regeneration is complete in about 2 weeks.
- Callus or thickening of the skin - because of hyperplasia of epidermal cells in response to a mechanical stimulus
35
What are induced and play a critical role in liver regeneration?
Several growth factors and cytokines (chemical messengers).
36
What types of cells cannot divide again once differentiated?
neurons, skeletal muscle cells.
37
Significant hyperplasia occurs in what areas?
1. epidermal and intestinal epithelial
2. hepatocytes
3. bone marrow cells
4. fibroblasts
Some hyperplasia is noted in bone, cartilage, and smooth muscle cells
38
Hormonal hyperplasia
occurs chiefly in estrogen-dependent organs, such as the uterus and breast.
39
Give an example of hormonal hyperplasia
After ovulation, for example, estrogen stimulates the endometrium to grow and thicken in preparation for receiving the fertilized ovum. If pregnancy occurs, hormonal hyperplasia, as well as hypertrophy, enables the uterus to enlarge
40
Pathological hyperplasia
abnormal proliferation of normal cells, usually in response to excessive hormonal stimulation or growth factors on target cells
41
What is the most common pathological hyperplasia
Most common - Pathological hyperplasia of the endometrium caused by an imbalance between estrogen and progesterone secretion, with over secretion of estrogen
Benign prostatic hyperplasia is another example which results from changes in hormone balance.
If hormonal imbalance is corrected, then hyperplasia regresses.
42
Dysplasia
- is not a true adaptive change
- refers to abnormal changes in the size, shape, and organization of mature cells
- atypical hyperplasia
43
Where does dysplastic changes often occur?
Epithelial tissue of the cervix and respiratory tract
- they are strongly associated with common neoplastic growth
- often adjacent to cancerous cells
44
Metaplasia
Reversible replacement of one mature cell type (epithelial, mesenchymal) by another, sometimes less differentiated cell type.
45
Give an example of metaplasia
The best example of metaplasia is replacement of normal columnar ciliated epithelial cells of the bronchial (airway) lining by stratified squamous epithelial cells - e.g. cigarette smoking. If stimulus is removed then can be reversed, if not, then dysplasia and cancerous transformation can occurs.
46
When does cellular injury occur?
When the cell is unable to maintain allostasis - a normal or adaptive steady state - in the face injurious stimuli or stress.
Injured cells may recover (reversible) or die (irreversible)
47
Give examples of injurious stimuli
1. Hypoxia
2. free radicals
3. infectious agents
4. physical and mechanical factors
5. immunological reactions
6. genetic factors
7. nutritional imbalances
48
What are the types of injuries?
1. Adaptation
2. Active cellular injury
3. reversible
4. Irreversible
5. Necrosis
6. Apoptosis or programmed cellular death
7. Autophagy
8. Chronic cellular injury
9. Accumulations or infiltrations
10. pathological calcification
49
What are the responses Adaptation?
Atrophy, hypertrophy, hyperplasia, metaplasia
50
What are the responses to Active cellular injury
Immediate response of entire cell
51
What are the responses to Reversible?
- loss of ATP
- cellular swelling
- detachment of ribosomes
- autophagy of lysosomes
52
What are the responses to Irreversible?
"Point of no return" structurally when severe vacuolization of mitochondria occurs and Ca++ moves into cell
53
What are the responses to Necrosis
Common type of cellular death with severe cell swelling and breakdown of organelles
54
What are the responses to Apoptosis
Cellular self destruction for elimination of unwanted cell populations
55
What are the responses to autophaghy?
Eating of self, cytoplasmic vesicles engulf cytoplasm and organelles, recycling factory
56
What are the responses to chronic cellular injury (subcellular alterations)
Persistent stimuli response may involve only specific organelles or cytoskeleton (e.g. phagocytosis of bacteria)
57
What are the responses to pathological calcifications?
Dystrophic and metastatic calcifications
58
The extent of cellular injury depends on what factors?
1. type
2. state (including level of cell differentiation and increased susceptibility to fully differentiated cells.)
3. adaptive processes of the cell
4. as well as the type, severity, and duration of the harmful stimulus
59
Give an example of a modifying factor that can profoundly influence the extent of injury?
Nutritional Status
60
Yes or No: Would 2 individuals exposed to an identical stimulus incur the same degree of cellular injury?
No
61
What are the biochemical mechanisms involved with cellular injury and death?
1. ATP depletion
2. Mitochondrial damage
3. Oxygen and oxygen free derived free radical membrane damage
4. Protein folding defects
5. DNA damage defects
6. Calcium level alterations
62
Give examples of common forms of cellular injury?
1. hypoxic injury - most common
2. free radicals and reactive oxygen species injury
3. chemical injury
63
Describe ATP depletion
- Loss of mitochondrial ATP and decreased ATP synthesis
- results include cellular swelling, decreased protein synthesis, decreased membrane transport, and lipogenesis --> all changes that contribute to loss if integrity of plasma membrane
64
Describe ROS - reactive oxygen species
Lack of oxygen is key in progression of cellular injury in ischemia (reduced blood supply); activated oxygen species (ROS, O2*–, H2O2, *OH) cause destruction of cell membranes and cell structure
65
Describe Ca++entry
Normally intracellular cytosolic calcium concentrations are very low; ischemia and certain chemicals cause an increase in cytosolic Ca++ concentrations; sustained levels of Ca++ continue to increase with damage to plasma membrane; Ca++ causes intracellular damage by activating a number of enzymes
66
Describe mitochondrial damage
Can be damaged by increases in cytosolic Ca++, ROS; two outcomes of mitochondrial damage are loss of membrane potential, which causes depletion of ATP and eventual death or necrosis of cell, and activation of another type of cellular death (apoptosis)
67
Describe Membrane damage
Early loss of selective membrane permeability found in all forms of cellular injury, lysosomal membrane damage with release of enzymes causing cellular digestion
68
Describe Protein misfolding, DNA damage
Proteins may misfold, triggering unfolded protein response that activates corrective responses; if overwhelmed, response activates cell suicide program or apoptosis; DNA damage (genotoxic stress) also can activate apoptosis
69
What is the single most common cause of cellular injury?
Hypoxia
70
What are the main consumers of Oxygen?
Mitochondria
71
________ are also possible hypoxia signalling molecules.
ROS
72
What is the most common cause of hypoxia?
Ischemia
73
What is somatic death?
Somatic death is the death of the whole person
74
How long after death does post mortem changes appear?
Within minutes, is diffuse and does not involve components of the inflammatory response.
75
What are the most notable manifestations of somatic death?
cessation of respiration and circulation
76
What happens to the body temp after death?
falls gradually immediately then more rapidly (around 1 degree celsius/hour). After 24 hours, body temp = environment. If death caused by infective disease, body temp may continue to rise for a short time.
77
Algor Mortis
Postmortem reduction of body temp.
78
Livor mortis
Purple discoloration after death. Happens when gravity causes blood to settle in the most dependent, or lowest tissues.
79
Rigor Mortis
Muscle stiffening - happens when acidic compounds accumulate within the muscles because of breakdown of carbs and depletion of ATP.
80
What muscles are initially affected with rigor mortis?
Smaller muscles , particularly the muscles of the jaw.
81
When does rigor mortis affect the whole body?
Within 12-14 hours
82
When does rigor mortis diminishes and body becomes flaccid?
at 36-62 hours.
83
When are signs of putrefaction generally obvious?
24-48 hours after death.
84
Postmortem autolysis
Release of enzymes and lytic dissolution
85
Describe Autophagy
- eating of self
- as a "recycling factory", it's a self-destructive process and a survival mechanism
- involves delivery of cytoplasmic contents to the lysosomes for degradation
86
What are the major forms of autophagy
1. Macroautophagy
2. Microautophagy
3. Chaperone-mediated authophagy
87
Describe macroautophagy?
involves with sequestration and transportation of parts of the cytosol in an autophagic vacuole (autophagosome)
88
What is microautophagy?
inward invagination of the lysosomal membrane for cargo delivery
89
Describe chaperone-mediated autophagy
chaperone-dependent proteins that direct cargo across the lysosomal membrane
90
What is apoptosis?
- An active process cellular destruction called program cellular death
- happens in normal and pathological tissue change
91
Give examples of pathological states that can involve death by apoptosis
1. Severe cellular injury
2. Accumulation of misfolded proteins
3. Infections (particularly viral)
4. Obstruction in tissue ducts
5. Dysregulated apoptosis
92
Describe apoptosis in relation to severe cellular injury?
When cellular injury exceeds repair mechanisms, the cell triggers apoptosis. DNA damage can result either directly or indirectly from production of free radicals.
93
Discuss apoptosis in relation to misfolded proteins?
This state may result from genetic mutations or free radicals. Excessive accumulation of misfolded proteins in the ER leads to a condition known as ER stress (see Chapter 1). ER stress results in apoptotic cellular death. This mechanism explains several degenerative diseases of the CNS and other organs
94
Discuss apoptosis in relation to infection
Apoptosis results directly from the infection or indirectly from the host immune response. Cytotoxic T lymphocytes respond to viral infections by inducing apoptosis and, therefore, eliminating the infectious cells. This process can cause tissue damage, and it is the same for cellular death in tumours and rejection of tissue transplants.
95
Discuss apoptosis in relation to tissue duct
In organs with duct obstruction, including the pancreas, kidney, and parotid gland, apoptosis causes pathological atrophy.
96
Discuss apoptosis in relation to Dysregulated Apoptosis
is either excessive or insufficient apoptosis and contributes further to disease. For instance, a low rate of apoptosis can permit the survival of abnormal cells, for example, mutated cells that can increase cancer risk. Defective apoptosis may not eliminate lymphocytes that react against host tissue (self-antigens), leading to autoimmune disorders. Excessive apoptosis is known to occur in several neuro-degenerative diseases, from ischemic injury (such as myocardial infarction and stroke), and from death of virus-infected cells (as seen in many viral infections).
97
What are the 2 different pathways that converge on caspase in relation to apoptosis?
1. Mitochondrial (intrinsic) pathway
2. Death receptor (extrinsic pathway)
98
What does cellular death eventually lead to?
Necrosis or cellular dissolution.
99
What is necrosis?
The sum of cellular changes after local cellular deathand the process of cellular digestion (autodigestion or autloysis)
100
What are the structural signs that indicate irreversible injury and progression to necrosis?
Dense clumping and progressive disruption both of genetic material and of plasma and organelle membranes.
101
What happens when membrane integrity is lost during necrosis?
Necrotic cell contents leak out and may cause the signaling of inflammation in surrounding tissue.
102
What happens in the alter stages of necrosis?
- Disruption of organelles occur
- karyolysis is underway (nuclear dissolution and lysis of chromatin from the action of hydrolytic enzymes)
- in some cells, nucleus shrinks and becomes small, dense mass of genetic material.
103
What is karyorrhexis
Fragmentation of the nucleus into smaller particles or nuclear dust.
104
Give examples of the type of Necrosis.
1. Coagulative Necrosis
2. Liquefative necrosis
3. Caseous necrosis
4. Fatty Necrosis
5. Gangrenous Necrosis
6. Gas Gangrene
105
Where does coagulative necrosis occur primarily?
Kidneys, heart, and adrenal glands.
106
What does coagulative necrosis result from ?
Hypoxia by severe ischemia or hypoxia caused by chemical injury, especially ingestion of mercuric chloride.
107
What do you call the area of coagulative necrosis?
Infarct
108
What causes coagulation in relation to coagulative necrosis?
It is a result of protein denaturation, which causes the protein albumin to change from a gelatinous, transparent state to a firm opaque state.
109
What commonly cause liquefactive necrosis?
It commonly results from ischemic injury to neurons and glial cells in the brain.
110
List some bacterial infection that can cause liquefactive necrosis?
Staphylococci, Streptococci, e. coli
111
What commonly causes caseous necrosis?
It usually results from tuberculous pulmonary infection especially by Mycobacterium tuberculosis.
112
Caseous necrosis is a combination of what types of necroses?
Coagulative and liquefactive.
113
Why does liquefactive necrosis readily affect dead brain tissue?
Because brain cells are rich in digestive hydrolytic enzymes and lipids and the brain contains little connective tissue.
114
Explain the process of liquefactive necrosis?
Cells initiate autodigestion by their own hydrolases, so the tissue becomes soft, liquefies, and segregates from healthy tissue, forming cysts.
115
Explain what happens in caseous necrosis.
The dead cells disintegrate, but the hydrolases do not completely remove all the debris. Tissues resemble clumped cheese in that they are soft and granular. A granulomatous inflammatory wall encloses areas of caseous necrosis.
116
What is fatty necrosis?
Fat necrosis is cellular dissolution caused by powerful enzymes, called lipases that occur in the breast, pancreas, and other abdominal structures
117
Where does fatty necrosis usually occur?
breast, pancreas, and other abdominal structures
118
Explain the process of fatty necrosis.
Lipases break down triglycerides, releasing free fatty acids that then combine with calcium, magnesium, and sodium ions, creating soaps (saponification). The necrotic tissue appears opaque and chalk-white.
119
What is the appearance of the necrotic tissue from fatty necrosis?
opaque and chalk-white.
120
What causes gangrenous necrosis?
It results from severe hypoxic injury, which commonly occurs because of arteriosclerosis, or blockage, of major arteries, particularly those in the lower leg
121
What type of gangrene is the result of coagulative necrosis?
Dry Gangrene
122
What does dry gangrene look like?
skin becomes very dry and shrinks, resulting in wrinkles, and its colour changes to dark brown or black.
123
How does wet gangrene develop?
It develops when neutrophils invade the site, causing liquefactive necrosis.
124
Where does wet gangrene usually occur?
Internal organs
125
Describe some of the manifestations of wet gangrene?
Area becomes cold, swollen, and black. A foul odor is present, and death is a possibility if systemic symptoms become severe.
126
What does gas gangrene result from?
This type of gangrene is the result of infection of injured tissue by one of many species of Clostridium.
127
Describe the process of Gas gangrene
These anaerobic bacteria produce hydrolytic enzymes and toxins that destroy connective tissue and cellular membranes and cause bubbles of gas to form in muscle cells. Gas gangrene can be fatal if enzymes lyse the membranes of red blood cells, destroying their oxygen-carrying capacity. Shock is the main cause of death.
128
What is the main cause of death with gas gangrene?
Shock
129
What is an important manifestation of cellular injury?
Intracellular accumulation of abnormal amounts of various substances and the resultant metabolic disturbances
130
What does cellular accumulations or infiltration results from ?
from sublethal, sustained injury of cells but also from normal (but inefficient) cell function.
131
What are the 2 categories of substances than can produce accumulations?
(1) normal cellular substances (such as excess water, proteins, lipids, and carbohydrates) and (2) abnormal substances, either endogenous (such as a product of abnormal metabolism or synthesis) or exogenous (such as infectious agents or a mineral).
132
Abnormal accumulations of substances can occur in what parts of the cell?
It can occur in the cytoplasm (often in the lysosomes) or in the nucleus
133
What are some of the reasons why abnormal accumulations occur?
(1) There is insufficient removal of the normal substance because of altered packaging and transport, such as what happens with fatty change in the liver, (e.g., steatosis).
(2) An abnormal substance, often the result of a mutated gene, accumulates because of defects in protein folding, transport, or abnormal degradation.
(3) There is inadequate metabolism of an endogenous substance (normal or abnormal), usually because of lack of a vital lysosomal enzyme, and these are called storage diseases.
(4) Harmful exogenous materials, such as heavy metals, mineral dusts, or microorganisms, accumulate because of inhalation, ingestion, or infection.
134
What is the most common degenerative change with cells?
Cellular swelling
135
In hypoxic injury, what does movement of fluids and ions into the cell associated with?
it is associated with failure of metabolism and loss of ATP production.
136
What happens during metabolic failure caused by hypoxia?
reduced levels of ATP and ATPase permit sodium to accumulate in the cell while potassium (K+) diffuses outward.
137
What happens when intracellular Na+ concentration increases?
increases osmotic pressure, drawing more water into the cell. The cisternae of the ER swell, rupture, and then unite to form large vacuoles that isolate the water from the cytoplasm, a process called vacuolation.
138
What is the process of vacuolation?
This is when the ER swell, rupture, and then unite to form large vacuoles that isolate the water from the cytoplasm
139
What is cytoplasmic swelling?
Oncosis
140
What happens with progressive vacuolation?
cytoplasmic swelling called oncosis
141
What happens when cellular swelling affects all the cells in an organ ?
the organ increases in weight and becomes distended and pale.
142
True of False: Cellular swelling is non-reversible and lethal
False - cellular swelling is reversible and sub-lethal. It is an earlier manifestation of almost all types of cellular injury.
143
What clinical manifestations are associated with cellular swelling?
high fever, hypokalemia, and certain infections
144
Where does lipids and carbs usually accumulate?
Spleen, liver, and CNS
145
What happens when lipids and carbohydrates accumulate in the CNS?
It can cause neurological dysfunction and severe intellectual disability. Lipids accumulate in Tay-Sachs disease, Niemann-Pick disease, and Gaucher's disease
146
What is the most common site of intracellular lipid accumulation or fatty change (steatosis)?
liver cells
146
What is the most common cause of fatty change in the liver in developed countries?
alcohol abuse
147
What are other causes of fatty change?
diabetes mellitus, protein malnutrition, toxins, anoxia, and obesity.
148
What happens once lipid fill the cells?
vacuolation pushes the nucleus and other organelles aside. The liver's outward appearance is yellow and greasy.
149
What are some of the mechanisms instigated by cellular injury that leads to lipid accumulation?
1. Increased movement of free fatty acids into the liver (starvation, e.g., increases the metabolism of triglycerides in adipose tissue, releasing fatty acids that subsequently enter liver cells)
2. Failure of the metabolic process that converts fatty acids to phospholipids, resulting in the preferential conversion of fatty acids to triglycerides
3. Increased synthesis of triglycerides from fatty acids (increased levels of the enzyme α-glycerophosphatase can accelerate triglyceride synthesis)
4. Decreased synthesis of apoproteins (lipid-acceptor proteins)
5. Failure of lipids to bind with apoproteins and form lipoproteins
6. Failure of mechanisms that transport lipoproteins out of the cell
7. Direct damage to the ER by free radicals released by alcohol's toxic effects
150
When does intracellular accumulations of glycogen occur?
It occur in genetic disorders called glycogen storage diseases and in disorders of glucose and glycogen metabolism.
151
What is the results of glycogen accumulation?
excessive vacuolation of the cytoplasm.
152
What is the most common cause of glycogen accumulation?
the disorder of glucose metabolism (i.e., diabetes mellitus)
153
What does protein provide to the cells?
It provides cellular structure and constitute most of the cell's dry weight.
154
How does accumulation of protein damage the cell?
1. Cellular organelle damage may occur when metabolites (enzymes produced when the cell attempts to digest some proteins) are released from lysosomes.
2. Additionally, when excessive amounts of protein are present in the cytoplasm, they may push against cellular organelles, disrupting organelle function and intracellular communication.
155
Where does excess of protein primarily accumulate?
1. pithelial cells of the renal convoluted tubules of the nephron unit
2. in the antibody-forming plasma cells (B lymphocytes) of the immune system
156
Where does endogenous pigments come from?
Endogenous pigments come from amino acids, for example (e.g., tyrosine, tryptophan). They include melanin and the blood proteins porphyrins, hemoglobin, and hemosiderin.
157
What is the most common exogenous pigment?
carbon (coal dust), a pervasive air pollutant in urban areas. Inhaled carbon interacts with lung macrophages and travels by lymphatic vessels to regional lymph nodes. This accumulation blackens lung tissues and involved lymph nodes.
Other exogenous pigments include mineral dusts containing silica and iron particles, lead, silver salts, and dyes for tattoos.
158
Where does melanin accumulate?
accumulates in epithelial cells (keratinocytes) of the skin and retina.
159
What is the function of melanin?
it protects the skin against long exposure to sunlight and is an essential factor in the prevention of skin cancer
160
What stimulates syntheses of melanin?
Ultraviolet light (e.g., sunlight)
161
What does melanin look like?
brown-black pigment
162
Where is melanin derived from?
derived from the amino acid tyrosine. Melanocytes synthesize this pigment and melanosomes, membrane-bound cytoplasmic vesicles store it.
163
What is the most essential of the normal endogenous pigment?
Hemoproteins
164
What's included as hemoproteins?
hemoglobin and the oxidative enzymes or cytochromes.
165
What can cause hemoprotein accumulation in cells?
Excessive storage of iron that transfers from bloodstream to cells
166
How does iron enter blood?
(1) tissue stores, (2) the intestinal mucosa (mainly the stomach), and (3) macrophages that remove and destroy dead or defective red blood cells.
167
The amount of iron in the blood plasma depends of what other factor?
It depends also on the metabolism of the major iron transport protein, transferrin.
168
What are the 2 forms of iron in tissue cells?
1. Ferritin
2. when increased levels of iron are present, as hemosiderin.
169
What is hemosiderin?
a yellow-brown pigment derived from hemoglobin.
170
What is hemosiderosis
is a condition in which excess iron is stored as hemosiderin in the cells of many organs and tissues.
171
What is hemosiderosis common in?
- is common in individuals who have received repeated blood transfusions or prolonged parenteral administration of iron.
- is also associated with increased absorption of dietary iron, and conditions where iron storage and transport are impaired, as well as hemolytic anemia (when there is excessive breakdown of red blood cells).
- Excessive alcohol (e.g., wine) ingestion also can lead to hemosiderosis.
172
What is hemochromatosis?
(a genetic disorder of iron metabolism and the most severe example of iron overload), are associated with liver and pancreatic cell damage.
173
What is bilirubin?
is a normal, yellow-to-green pigment of bile derived from the porphyrin structure of hemoglobin.
174
3 circumstances that can lead to hyperbilirubinemia?
(1) mass destruction of red blood cells (erythrocytes), such as in hemolytic jaundice; (2) diseases affecting the metabolism and excretion of bilirubin in the liver; and
(3) diseases that cause obstruction of the common bile duct, such as gallstones or pancreatic tumours. Certain medications (specifically chlorpromazine [Largactil] and other phenothiazine derivatives), estrogenic hormones, and halothane (Fluothane) (an anaesthetic) can cause the obstruction of normal bile flow through the liver.
175
What are the 2 causes that unconjugated bilirubin causes?
1. uncoupling of oxidative phosphorylation and
2. a loss of cellular proteins.
These two changes could cause structural injury to the various membranes of the cell.
176
What is an important mechanism of cellular calcification?
influx of extracellular calcium in injured mitochondria.
177
Pathological calcification can be _______ or ________
dystrophic or metastatic
178
Where does dystrophic calcification occur
1.occurs in dying and dead tissues in areas of necrosis
179
Where is dystrophic calcification present?
It is present in chronic tuberculosis of the lungs and lymph nodes, advanced atherosclerosis (narrowing of the arteries because of plaque accumulation), and heart valve injury, and centre of tumours.
180
What does calcification of heart valve interfere with?
interferes with their opening and closing and causes heart murmurs
181
What can predispose arteries to severe narrowing and thrombosis which can lead to MI?
Calcification of coronary artery
182
Psammoma bodies
Several layers of calcium salts that clump together. They resemble grains of sand.
183
What does metastatic calcification consist of?
mineral deposits that occur in undamaged normal tissues as the result of hypercalcemia
184
What are the conditions that can cause hypercalcemia?
hyperparathyroidism, toxic levels of vitamin D, hyperthyroidism, idiopathic hypercalcemia of infancy, Addison's disease (adrenocortical insufficiency), systemic sarcoidosis, milk-alkali syndrome, and the increased bone demineralization that results from bone tumours, leukemia, and disseminated cancers.
185
What is urate?
major end product of purine catabolism because of the absence of the enzyme, urate oxidase.
186
What are systemic manifestations of cellular injury?
1. Fever
2. Increased HR
3. Leukocytosis
4. Pain
5. Presence of cellular enzyme
6. Lactate dehydrogenase (LDH) (LDH isoenzymes)
7. Creatine kinase (CK) (CK isoenzymes)
8. Aspartate aminotransferase (AST/SGOT)
9. Alanine aminotransferase (ALT/SGPT)
10. Alkaline phosphatase (ALP)
11. Amylase
12. Aldolase
