Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Foundations of Disease > Exam 1: Cell Injury and Cell Death > Flashcards

Exam 1: Cell Injury and Cell Death Flashcards

1
Q

Response to Stress

A
  • Cells and organs in homeostasis
  • Response to stress ⇒ adaptation or death
  • Response dependent on severity and length of stress
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Adaptations

A

In response to changes in physiologic and pathologic stimuli to maintain homeostasis.

When stress removed, can recover without harm.

Includes:

  • Hypertrophy
  • Hyperplasia
  • Atrophy
  • Change in phenotype
    • Metaplasia
    • Dysplasia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Hypertrophy

A

Increase in cellular size and functional activity.

  • Physiologic
    • Muscle hypertrophy w/ inc. workload
      • ↑ protein synthesis ⇒ ↑ myofilament size ⇒ ↑ force generation
      • Ex:
        • Bodybuilder ⇒ inc. demand
        • Heart ⇒ chronic hemodynamic overload
  • Pathologic
    • Cancer
    • Response to injury
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Cardiac Hypertrophy

Pathogenesis

A
  1. Mechanical sensors ⇒ production of growth factors and agonists
  2. Activation of signal transduction pathways
  3. Activation of transcription factors
  4. Inc. synthesis of muscle proteins
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Hyperplasia

A

Increase in cell number.

  • Occurs in response to stimuli
  • Can occur with hypertrophy
  • Only seen in tissues where cells can divide
  • Physiologic vs Pathologic
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Physiologic Hyperplasia

Examples

A
  • Breast glandular epithelium
    • Puberty or pregnancy
  • Liver regeneration
    • Regenerate after donation
  • Bone marrow
    • Make more RBCs after bleed or hemolysis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Pathologic Hyperplasia

Examples

A
  • Endometrial hyperplasia
    • Causes abnormal bleeding
    • Due to excess estrogen ⇒ imbalance between estrogen/progesterone
  • Benign prostatic hyperplasia
    • In response to androgens
    • Increases with age
    • No increased risk for neoplasm
  • Response to viral infection
    • Ex. HPV ⇒ warts
      • Viral factors can interfere with host proteins that regulate cell proliferation
      • Can be a cancer precursor
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Atrophy

A
  1. ↓ cell size & organelles
    • ↓ metabolic demands
    • Attempt to prolong survival
    • May diminish cell function
    • May lead to irreversible injury and death
  2. ↓ size of organ or tissue
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Physiologic Atrophy

Examples

A
  • Embryonic development
  • Shrinkage of uterus after delivery
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Pathologic Atrophy

Examples

A
  • Decreased workload
    • Atrophy of disuse
  • Loss of innervation
  • Diminished blood supply
    • Seen in brain w/ age
  • Inadequate nutrition
    • Marasmus ⇒ cachexia
  • Loss of endocrine stimulation
    • Uterus after menopause
  • Pressure
    • Enlargeing tumor compresses normal tissue
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Protein and Organelle

Clearance

A

Two pathways to clear damaged proteins and organelles:

  1. ↓ protein synthesis
    • In response to ↓ metabolic activity
  2. ↑ protein degradation
    • Ubiquitin-proteasome pathway
      • Activation of ubiquitin ligases
      • Ubiquitin attached to proteins
      • Degraded in proteasomes
    • Autophagy
      • Cells “eats” it own components
      • Debris may remain as residual bodies ↑ lipofuscin granules
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Metaplasia

A

One cell type is replaced by another normal cell type.

  • Reversible change
  • Usually in response to stress
  • New cell type more able to withstand stress
  • Stem cells ‘reprogrammed’ to differentiate along new path
    • Signaled by cytokines, growth factors, ECM components
    • Promotes expression of genes that drive differentiation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Squamous Metaplasia

A
  • Columnar ⇒ squamous epithelium
  • Most common epithelial metaplasia
  • In areas of chronic irritation
    • Ex. bronchi of smokers
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Barrett’s Esophagus

A

“Intestinal metaplasia”

  • Squamous ⇒ columnar epithelium w/ globlet cells
  • Due to gastric reflux
  • Can lead to cancer
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Osseous (cartilaginous)

Metaplasia

A
  • Production of cartilage or bone in areas of tissue injury
  • Causes:
    • Chronic irritation
    • Stress
    • Tissue damage
  • Ex:
    • Irritation due to dentures
    • Injury to muscle ⇒ myositis ossificans
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Cell Injury

A

Reversible vs Irreversible

  • Stimulus
    • Limit of adaptive response exceeded
    • Exposed to injurious agent or stress
    • Deprived of essential nutrients
    • Compromised by mutations that affect essential cellular constituents
  • Time lag between injury and effects
    • Signs of reversible injury takes longer
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Cellular Injury

Causes

A
  • Oxygen deprivation
    • Hypoxia, ischemia
  • Physical agents
    • Mechanical, temp, radiation, electrical, pressure
  • Chemical agents
    • Pollutants, poisons, drugs, metabolists
  • Infectious agents
    • Virus, bacterial, fungi, parasites
  • Immune reactions
    • Exogenous, autoimmune
  • Genetic derangements
    • Enzymes, structural proteins
  • Nutritional imbalance
  • Proliferation errors (DNA)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Reversible Injury

Changes

A
  • Functional changes
    • ↓ oxidative phosphorylation
      • Depletes ATP and glycogen stores
    • ↓ transporter function
      • Loss of membrane activity and integrity
    • Defects in protein synthesis
    • Cytoskeletal damage
    • DNA damage
  • Morphological changes:
    • Cellular swelling ⇒ due to ∆ in ion concentration and water influx
    • Mitochondrial swelling & amorphous densities
    • RER swelling & ribosome detachment
    • Clumping of nuclear chromatin
    • Membrane blebbing & loss of microvilli
    • Cytoplasmic vacuoles
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Cell Injury

Mechanisms

A
  • Mitrochondrial damage
    • ↓ ATP
    • ↑ ROS
  • Calcium entry
  • Membrane damage
  • Protein misfolding
  • DNA damage
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Depletion of ATP

Causes

A
  • ATP produced through:
    • Ox Phos of ADP
    • Glycolysis
  • ↓ [ATP] caused by:
    • ↓ O2 supply
    • ↓ nutrient supply
    • Mitochondrial damage
    • Toxins
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Depletion of ATP

Effects

A

If [ATP]intracellular falls to 5-10% of normal:

  • ↓ Na/K pump activity ⇒ cell swelling
  • ∆ cellular metabolism ⇒ shift to anaerobic glycolysis
    • Depletes glycogen stores
    • Produces lactic acid
      • ↓ cellular pH ⇒ ↓ enzyme activity
  • ↓ calcium pump activity ⇒ Ca2+ influx ⇒ damage to many cellular components
  • Ribosome detach from RER & polysomes dissociate ⇒ ↓ protein synthesis
  • ↑ protein misfolding ⇒ accumulation in RER ⇒ activation of misfolded protein response ⇒ cell injury & cell death
  • Irreversible damage to mitochondrial & lysosomal membranes ⇒ necrosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Mitochondrial Damage

A
  • Causes:
    • ↑ [Ca2+]cytosol
    • ROS
    • O2 deprivation
  • Types of mitochondrial damage:
    • Formation of mitochondrial permeability pore ⇒ failure of ox phos ⇒ ↓ [ATP]
    • Abnormal ox phos ⇒ ↑ [ROS]
    • Release of sequestered proteins from intermembrane space ⇒ apoptosis
      • Ex. cytochrome C & BCL proteins that activate caspases
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Loss of Calcium Homeostasis

A
  • Caused by ↓ ATP ⇒ influx of calcium
  • Key event in cell death
  • ↑ [Ca2+]intracellular effects:
    • Irreversibly poisons mitochondria
    • Inhibits many cellular enzymes
    • Activation of lytic enzymes
      • Phospholipases, proteases, endonucleases, ATPases
    • Initiates free radical formation
    • Denatures cellular proteins
      • Can lead to initiation of unfolded protein response
    • Activation of apoptosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Free Radicals

Characteristics

A
  • Have a single unpaired e- in an outer orbital
  • Extremely reactive with cellular macromolecules
  • ROS are a type of oxygen-derived free radical generated within cells
  • Build up if not scavenged and disposed of properly
  • Initiates autocatalytic rxns ⇒ propagates more free radicals
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Free Radical

Generation

A
  • Redox rxns during normal metabolism
    • Small amount of partially reduced intermediates generated
    • Superoxide anion, hydrogen peroxide, hydroxyl ions
  • Absorption of radiant energy (UV, X-rays) and ionizing radiation
    • Hydrolyzes water ⇒ free radicals
  • Activated WBCs generate ROS during inflammation (respiratory burst)
  • Enzymatic metabolism of exogenous chemicals/drugs
  • Transition metals (Fe, Cu) can donate or accept free electrons during rxns
    • Can catalyze formation of TOS
    • Binding to storage/transport proteins reduces reactivity
  • Nitric oxide can act as a free radical
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Free Radical

Removal

A
  • Inherently unstable ⇒ decay spontaneously
  • Cells have non-enzymatic & enzymatic mechanisms to remove free radicals
    • Non-enzymatic
      • Antioxidants ⇒ prevent formation or inactivate/scavange free radicals
        • Vit E, A, and C
        • Glutathione
      • Free Fe and Cu
    • Enzymatic ⇒ enzymes act as free radical scavening systems
      • Catalase, superoxide dismutase, glutathione peroxidase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Free Radical

Pathologic Effects

A
  1. Lipid peroxidation in plasma/organellar membranes
    • Attack double bonds in unsaturated FAs of membrane lipids
    • Generates peroxide
    • Results in autocatalytic chain reaction ⇒ propagation
    • Causes membrane damage
  2. Oxidative modification of proteins
    • Damage enzyme active sites
    • Disrupt conformation of structural proteins
    • Enhance degradation of misfolded proteins
  3. Lesions in DNA
    • Single or double stranded breaks in DNA
    • Crosslinking of strands
      • Implicated in cell aging and malignancy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Membrane Permeability

Defects

A
  • Mechanisms of injury:
    • ROS ⇒ lipid peroxidation
    • ↓ phospholipid synthesis
    • ↑ phospholipid breakdown
      • Products accumulate & have detergent effect on membranes
    • Cytoskeletal abnormalities
      • Due to proteases affected by ↑ cytosolic calcium
  • Results in damage to:
    • Mitochondrial membranes ⇒ apoptosis
    • Plasma membranes
    • Lysosomal membranes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

DNA and Protein

Damage

A
  • Cell initiates suicide program if:
    • DNA damage too severe to be corrected
    • Level of misfolded proteins too high
  • Results in death by apoptosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Ischemic and Hypoxic

Injury

A
  • Ischemia results from hypoxia due to ↓ blood flow
    • Usually due to blockage in arterial flow
    • Can be due to reduced venous drainage
      • Worsens hypoxia by also affecting anerobic energy generation
  • Reversible if oxygen flow restored in time
  • Organs respond differently to hypoxia d/t differences in metabolic activity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Organ Response to Anoxia

A

Cell death will begin in:

  • Neurons ⇒ 3-5 minutes
  • Myocardia ⇒ 20-30 minutes
  • Renal tubule cells ⇒ 30-60 minutes
  • Hepatocytes ⇒ 1-2 hours
  • Skeletal muscle ⇒ many hours
  • CT ⇒ many hours
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Chemical (Toxic) Injury

A
  • Direct toxicity
    • Chemicals injure cells by combining with molecular components
    • Ex. mercuric chloride poisoning, cyanide, chemotherapy
  • Conversion to toxic metabolites
    • Usually done by cytochrome P-450 mixed function oxidases
    • Ex. carbon tetrachloride, acetaminophen
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

___ leads to cell death.

A

Irreversible cell injury

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

‘Point of no return’ between reversible and irreversible damage characterized by…

A
  • Inability to reverse mitochondrial dysfunction
  • Lack of ox phos and ATP generation
  • Profound disturbances in membrane function
35
Q

Reversible vs Irreversible

Cell Injury

36
Q

Cell Death

A
  • End result of progressive cell injury
  • Many pathologic causes ⇒ ischemia, infection, toxins
  • Can be a normal process ⇒ embryogenesis, maintaining homeostasis
  • Two pathways ⇒ necrosis & apoptosis
37
Q

Necrosis

Overview

A
  • Always pathological
    • Ischemia, toxins, infections, trauma
  • Results from cell membrane damage
    • Loss of ion homeostasis
    • Cell contents leak into EC space ⇒ inflammatory response
    • Lysosomal enzymes enter cytoplasm & digest cell ⇒ necrosis
38
Q

Necrosis

Morphological Changes

A

Takes many hours for histologic or gross changes to be visible.

  • Cytoplasmic changes
    • ↑ eosinophilia
      • Loss of RNA
      • Denatured proteins
    • Vacuoles
    • Myelin figures
      • From damaged cell membranes
      • Degraded into FA, may calcify
  • Nuclear changes
    • Karyolysis ⇒ nuclear fragmentation
    • Pyknosis ⇒ nuclear contration
    • Karyorrhexis ⇒ fragmentation of pyknotic nuclei
  • Plasma membrane destruction
    • Enzymes & proteins leak out into ECM and blood
    • Detectable in blood within 2 hours of necrosis
39
Q

Coagulative Necrosis

A
  • Typically caused by ischemia or infarction
  • Dead tissue structure preverved for several days
    • Area called an infarct
  • Injury denatures enzymes ⇒ no proteolysis of dead cells ⇒ see eosinophilic cells without nuclei
  • Dead cells eventually cleared by WBCs via phagocytosis and lysosomal digestion
  • Typically seen with MI’s
40
Q

Liquefactive Necrosis

A
  • Results from focal bacterial or fungal infections
  • PMNs and Mφ degrade necrotic material and pathogen ⇒ pus
  • Seen in CNS s/p hypoxic injury
41
Q

Gangrenous Necrosis

A

(Clinical term)

  • Limb ischemia ⇒ coagulative necrosis ⇒ dry gangrene
  • Superimposed bacterial infection ⇒ liquefactive necrosis ⇒ wet gangrene
42
Q

Caseous Necrosis

A
  • ‘Cheese-like’ central necrotic area of a granuloma
  • Seen in tuberculosis and some other infectious
  • Caseation appears pink, amorphous, and granular
43
Q

Fat Necrosis

A
  • Focal areas of destruction
  • Usually specific to the release of pancreatic lipases or trauma to the breast
  • Fat reacts with calcium ⇒ saponification ⇒ soap
  • Appears chalky-white grossly
  • Shows outlines of necrotic fat cells microscopically
44
Q

Saponification

A

Deposition of chalky white material in areas of fat necrosis.

  • Results from combo of FA’s released from intracellular stores + extracellular calcium
  • Ex. dystrophic calcification
  • Serum calcium is normal
45
Q

Apoptosis

Overview

A
  • Programmed cell death ⇒ highly regulated
  • Serves many normal functions
  • Activated by either an intrinsic or extrinsic pathway
    • Relies on sequential activation of proteases through cleavage or caspase cascades
  • No inflmmatory reaction triggered
46
Q

Physiologic Apoptosis

Examples

A

Serves many normal functions:

  • Response to DNA or protein damage
  • Embryologic development
    • Ex. Webs between fingers
  • Tissue remodeling
  • Normal turnover
  • Involution of hormone-dependent tissues
  • Cell loss in proliferating cell populations
    • Ex. lymphocytes that don’t express useful antigen receptors
  • Elimination of self-reactive lymphocytes
  • Death of neutrophils after activation
47
Q

Pathologic Apoptosis

Examples

A
  • After exposure to toxins
  • Death of cells with mutations or DNA damage
    • Removes potentially cancerous cells
  • Improperly folded proteins
    • Caused by mutations or free radical damage
    • Accumulates in ER ⇒ ER stress ⇒ apoptosis
  • Death of infected cells
    • Viral infections ⇒ adenovirus, HIV
    • Host immune responses ⇒ hepatitis
  • T-cell mediated mechanisms
    • Kill tumor cells
    • Reject transplants
  • Atrophy in parenchymal glands when ducts obstructed
48
Q

Apoptosis

Morphological Changes

A
  • Degradation of cellular DNA and proteins
  • Organelles tightly packed ⇒ cell shrinkage
  • Chromatin condensation
    • Aggregates under nuclear membrane
    • Nucleus may break up
  • Formation of cytoplasmic blebs & apoptotic bodies
    • Membranes remain intact
  • Phagocytosis of apoptotic cells or cell bodies before materials leak out ⇒ no inflammatory response
49
Q

Apoptosis

Mechanism

A
  • Results from activation of enzymes
    • Caspases
      • Inactive proenzymes
      • Must undergo enzymatic cleavage for activation
      • Cleaved caspases are a marker of apoptotic cells
  • Activation depends on balance between pro- and anti- apoptotic signals
  • Two phases:
    1. Initiation ⇒ some caspases become active
    2. Execution ⇒ other caspases trigger degradation of cellular components
50
Q

Apoptosis

Intrinsic Initiation Pathway

A

“Mitochondrial pathway”

  • Major mechanism
  • Results from ↑ permeability of outer mitochondrial membrane
  • Releases pro-apoptotic molecules into cytosol
    • Cytochrome C ⇒ initiates apoptosis
    • BCL2 family ⇒ controls release
      • Some anti-apoptotic ⇒ BCL-2, BCL-XL, MCL-1
      • Some pro-apoptotic ⇒ BAX and BAK
      • Some are sensors ⇒ regulate the balance
  • Path activates initiator caspase-9
51
Q

Apoptosis

Extrinsic Initiation Pathway

A

“Death Receptor-Initiated Pathway”

  • Triggered by activation of death receptors on plasma membrane of some cells
  • Death receptors
    • Members of TNF receptor family
    • ‘Death domain’ site required
      • Protein-protein interactions delivers apoptotic signals
  • Type I TNF receptor (TNFR1) ⇒ best known
  • Fas (CD95) receptor ⇒ found on many cells
    • Binds Fas ligand (FasL)
      • Found on T cells that recognize self-Ag
        • Eliminate self-reactive lymphocytes
      • Found on some cytotoxic T-cells
        • Kill virus-infected and tumor cells
    • Fas-FasL binding brings together Fas molecules
      • Forms binding site for FADD (Fas-associated death domain)
      • FADD binds inactive Caspase-8 via death domain ⇒ activation
  • Path activates initiator caspase-8 and caspase-10
52
Q

Apoptosis

Execution Phase

A

Intrinsic and extrinsic initiation pathways converge at the activation of executioner caspases:

  • Executioner caspases ⇒ caspase-3 and caspase-6
    • Acts on cellular components
    • Results in:
      • Cleavage of DNA
      • Degradation of nuclear matrix
      • Degradation of proteins
      • Etc.
  • Apoptotic bodies removed by phagocytes
    • May be recruited by cell surface markers on apoptotic bodies
      • Thrombospondin
      • C1q
53
Q

Decreased Apoptosis

A

Defective apoptosis ⇒ increased cell survival:

  • Survival of abnormal cells
    • TP53 mutations
      • Defective DNA repair
      • ↑ susceptibility to accumulation of mutations
      • ↑ cancer risk
        • Most common genetic abnl found in human cancers
  • Failure to remove self-reactive and dead cells
    • ↑ risk of autoimmune disorders
54
Q

Increased Apoptosis

A

Increased apoptosis ⇒ excessive cell death

  • Neurodegenerative diseases
    • Apoptosis due to mutations and misfolded proteins
  • Ischemic injury
    • E.g. MI and stroke
  • Death of virus infected cells
55
Q

Apoptosis

vs

Necrosis

56
Q

Autophagy

Overview

A
  • Cell digests its own constiuents
  • Protects against nutriend deprivation
  • Performs intracellular “quality control’
  • Involved in elimination of intracellular infections
  • Rodels cellular components to meet needs
57
Q

Autophagy

Types

A
  1. Chaperone-mediated autophagy
  2. Microautophagy
  3. Macroautophagy
58
Q

Chaperone-mediated Autophagy

A

Direct translocation across lysosomal membrane by chaperone proteins.

59
Q

Microautophagy

A

Inward invagination of lysosomal membrane for delivery.

60
Q

Macroautophagy

A

Sequester and transport portions of cytoplasm in double-membrane bound autophagic vacuoles (autophagosome) to lysosomes.

Primary mode of autophagy.

61
Q

Intracellular Accumulations

A
  • Material accumulates in cytosol, organelles, or nucleus
  • May be reversible or irreversible
  • Can cause damage if extreme
62
Q

Metabolic Derangement

Pathways

A
  1. Inadequate removal of normal substances
    • Due to defect in packaging or transport
    • Ex. Steatosis in liver
  2. Accumulation of abnormal endogenous substances
    • Due to defective folding, packaging, or secretion
  3. Failure to degade metabolites
    • Due to inherited enzyme deficiences
    • “Storage diseases”
  • Deposit and accumulate abnormal exogenous substances
    • Due to inability to degrade or excrete substances
    • Ex. carbon in macrophages
63
Q

Steatosis

A

“Fatty change”

  • Abnormal accumulation of lipids/TAGs in parenchymal cells
  • Seen in liver and other organs
  • Causes:
    • Toxins
    • Protein malnutition
    • DM
    • Obesity
    • Anoxia
64
Q

Atherosclerosis

A
  • Smooth muscle cells and macrophages filled with lipid vacuoles
    • Contains mostly cholesterol and cholesteryl esters
  • Forms plaques on blood vessel walls
65
Q

Xanthomas

A

Cholesterol accumulation in macrophages in subepithelial CT of skin and tendons.

66
Q

Cholesterolosis

A

Accumulation of cholesterol-laden macrophages in lamina propria of the gallbladder.

67
Q

Niemann-Pick Disease

Type C

A

Lysosomal storage disorder leading to abnormal accululation of cholesterol in cells.

68
Q

Protein Accumulations

Appearance

A

Appears as rounded eosinophilic droplets, vacuoles, or aggregates in the cytosol.

69
Q

Protein Droplets

A

Protein resorption droplets in proximal renal tubules.

Found in patients with protein loss via urine.

70
Q

Immunoglobulin accumulation in plasma cells are called…

A

Russell bodies

71
Q

Alpha 1 Antitrypsin Deficiency

A

Defective intracellular transport and secretion of critical proteins.

Material builds up in ER of hepatocytes.

72
Q

Cytoskeletal Protein

Accumulation

A
  • Alcoholic Hyaline
    • Made of keratin intemediate filaments
    • Accumulates in the liver
  • Amyloid
    • Accumulates inside and between cells
    • Many organs affected
73
Q

Hyaline Change

A
  • Homogeneous, glassy pink material
  • Accumulates inside or between cells
  • Non-specific marker for cell injury
  • Extracellular hyaline can be seen in walls of arterioles with chronic HTN
74
Q

Glycogen Accumulation

A
  • Stored in healthy cells
  • Can be deposited in excessive amounts w/ abnormalities in glucose or glycogen metabolism
  • Appears as clear vacuoles in cytoplasm
    • Stained with PAS
  • Accumulates in glycogen storage diseases
75
Q

Exogenous Pigment

Accumulation

A
  • Coal dust (anthracotic pigment)
    • Accumulates in lungs and lymph nodes
    • Excessive amounts can produce serious disease
    • Ex. Coal workers pneumoconiosis
  • Tattoos
    • Pigments phagocytosed by derml macrophages
76
Q

Endogenous Pigment

Accumulation

A
  • Lipofuscin
  • Melanin
  • Hemosiderin
77
Q

Lipofuscin

A
  • Golden brown fine granules
  • ‘Wear and tear’ pigment
  • Contains lipid and proteins from membranes
  • Does not cause injury
  • Increases with age
  • Often seen in liver and heart
78
Q

Hemosiderin

A
  • Golden-brown granules
  • Derived from hemoglobin
  • Forms where there is local or systemic excess of iron
  • Normally see small amounts in macrophages
    • Bone marrow
    • Spleen
    • Liver
  • Local excess can accumulate in areas of bleeding
  • Systemic excess causes deposition in many tissues ⇒ hemosiderosis
79
Q

Abnormal deposition of calcium salts is called…

A

pathologic calcification

80
Q

Dystrophic Calcification

A
  • Local deposition of calcium in dying tissues
  • Serum calcium levels normal
  • See fine, white clumps w/ gritty texture
    • Basophilic on H&E
81
Q

Metastatic Calcification

A
  • Deposition of calcium salts in normal tissue
  • See hypercalcemia
  • May affect GI mucosa, kidneys, lungs, and blood vessels
  • If very severe, can affect organ function
82
Q

Cellular Aging

Overview

A

Progressive decline in cellular function and viability.

Results from:

  • Genetic abnormalities ⇒ mechanistic alterations
  • Accumulation of cellular and molecular damage
    • Due to exposure to exogenous influences
83
Q

Cellular Aging

Mechanisms

A
  • DNA damage
    • DNA repair mechanisms unable to correct all errors
    • Damage accumulates over time
    • Werner syndrome ⇒ see premature aging
  • Cellular senescence
    • Normal cells stop dividing after a fixed number of divisions
      • Telomeres shorten each time
      • Telomerase absent in most somatic tissues
      • Cancer cells have reactivated telomerase ⇒ proliferates indefinitely
    • Become arrested in a non-diving state ⇒ senescence
  • Defective protein homeostasis
  • Deregulated nutrient sensing
    • Caloric restriction shown to increase lifespan
      • Associated with IGF-1

Foundations of Disease (46 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions