Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

*USMLE Step 1, General Principles > Growth Adaptations, Cellular Injury, and Cell Death > Flashcards

Growth Adaptations, Cellular Injury, and Cell Death Flashcards

1
Q

Hypertrophy - Mechanism

A

Gene activation, protein synthesis, production of organelles

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

Hyperplasia - Mechanism

A

Production of new cells from stem cells or resting cells

  1. Labile (stem) cells - Continuously divide
  2. Stable cells - Resting cells in Go phase of cell cycle that may be stimulated to enter cell cycle
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Atrophy - Mechanism (2)

A
  1. Decrease in cell size
    a. Increased catabolism of cell organelles and reduction of cytosol via autophagy in which autophagic vacuoles fuse with lysosomes
    b. Increased catabolism of proteins by ubiquitin-proteasome pathway and decreased protein synthesis
  2. Decrease in cell number by apoptosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Metaplasia - Mechanism

A

Reprogramming of stem cells to utilize progeny cells with a different pattern of gene expression

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

Metaplasia - Barrett esophagus

A

Squamous epithelium –> Non-ciliated columnar epithelium with mucus-secreting cells and goblet cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Metaplasia - Mainstem bronchus (smoking)

A

Pseudostratified columnar epithelium –> Squamous epithelium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Metaplasia - Schistosoma haematobium infection (urinary bladder)

A

Transitional (urogenital) epithelium –> Squamous epithelium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Metaplasia - Myositis ossificans

A

Mesenchymal tissue –> Bone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Metaplasia - Keratomalacia

A

Specialized epithelium (conjunctivae) –> Keratinizing, stratified squamous epithelium

(Vitamin A deficiency)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Dysplasia - Mechanism

A

Disorderly proliferation of cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Dysplasia - Microscopic features (2)

A
  1. Increased mitotic activity with NORMAL mitotic spindles

2. Increased nuclear size and chromatin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Pathologic metaplasia without risk of progression to dysplasia and neoplasia?

A

Apocrine metaplasia of the breast (fibrocystic change)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Reversibility

  • Metaplasia
  • Dysplasia
  • Neoplasia
A
  • Metaplasia and dysplasia reversible

- Neoplasia irreversible

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Hypoxia

A

Inadequate oxygenation of tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

PaO2 - Contributing factors (4)

A
  1. Percent O2 in inspired air
  2. Atmospheric pressure
  3. Ventilation (PAO2 in the lungs)
  4. Perfusion and diffusion (Normal O2 exchange in the lungs through the alveolar-capillary membrane)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

SaO2 - Contributing factors (5)

A
  1. Percent O2 in inspired air
  2. Atmospheric pressure
  3. Ventilation (PAO2 in the lungs)
  4. Perfusion and diffusion (Normal O2 exchange in the lungs through the alveolar-capillary membrane)
  5. Valence of heme iron in Hb

Fe2+ (ferrous, reduced) binds O2
Fe3+ (ferric, oxidized) does NOT bind O2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Hypoxia - Clinical findings (4)

A
  1. Cyanosis - Bluish discoloration of the skin and mucuous membranes (SaO2 < 80%)
  2. Confusion
  3. Cognitive impairment
  4. Lethargy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Oxidative phosphorylation (electron transport chain) - Cellular location

A

Inner mitochondrial membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Causes of tissue hypoxia (3)

A
  1. Ischemia
  2. Hypoxemia
  3. Decreased O2 carrying capacity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Ischemia - Definition

A

Decreased arterial blood flow to tissue or venous outflow from tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Hypoxemia - Definition

A

Decrease in PaO2 (PaO2 < 60 mm Hg, SaO2 < 90%)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Causes of hypoxemia (6)

A
  1. Decreased inspired PO2 (PiO2)
  2. Respiratory acidosis
  3. Ventilation defect
  4. Perfusion defect
  5. Diffusion defect
  6. Cyanotic congenital heart disease
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Hypoxemia: Causes of decreased PiO2 (2)

A
  1. Breathing at high altitude

2. Breathing reduced %O2 mist

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Hypoxemia: Respiratory acidosis - Definition

A

Retention of CO2 in the lungs

Increased PACO2 always produced decreased PAO2 (Dalton’s law - PO2 + PCO2 + PN2 = 760 mm Hg)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Hypoxemia: Ventilation defect - Definition
- Lung perfused but not ventilated | - Impaired O2 delivery to alveoli
26
Hypoxemia: Perfusion defect - Definition
Lung ventilated but not perfused
27
Hypoxemia: Diffusion defect - Definition
Decreased diffusion of O2 through the alveolar-capillary interface Examples - Interstitial pulmonary fibrosis, pulmonary edema
28
Hypoxemia: Cyanotic congenital heart defect - Definition
Shunting of venous blood into arterial blood causes a drop in PaO2
29
Causes of decreased O2-carrying capacity (4)
1. Anemia 2. Methemoglobinemia (metHb) 3. Carbon monoxide (CO) poisoning 4. Factors causing a left-shifted Hb-O2 dissociation curve
30
Methemoglobinemia - Definition
Hb with oxidized Fe3+ (ferric iron) groups
31
Methemoglobinemia - Causes (3)
1. Oxidant stress - Nitrite- or sulfur-containing drugs 2. Congenital deficiency of cytochrome b5 reductase 3. Decreased levels of cytochrome b5 reductase (newborns, until approx. 4 months of age)
32
Methemoglobinemia - Mechanism of hypoxia (2)
1. metHb decreases the number of O2-binding sites, since O2 cannot bind Fe3+ in metHb 2. metHb impairs O2 unloading (left-shifts Hb-O2 dissociation curve) by stabilizing R state
33
Methemoglobinemia - Pathognomonic clinical finding
Chocolate-colored blood (increased deoxy-Hb)
34
Methemoglobinemia - Treatment (2)
IV methylene blue, vitamin C
35
Cytochrome b5 reductase system
Cytochrome b5 reductase catalyzes the enzymatic reduction of metHb and the enzymatic oxidation of NADH Fe3+ reduced to Fe2+ NADH oxidized to NAD+
36
NADPH-methemoglobin reductase system
NADPH-methemoglobin reductase catalyzes the enzymatic reduction of metHb and the enzymatic oxidation of NADPH - Located in the pentose phosphate shunt Fe3+ reduced to Fe2+ NADPH oxidized to NADP+
37
Methemoglobinemia - IV methylene blue (MOA)
Accelerates the enzymatic reduction of metHb by NADPH-methemoglobinemia reductase - NOT normally operational in reducing metHb
38
Carbon monoxide poisoning - Mechanism of hypoxia (3)
1. CO-Hb decreases the number of O2-binding sites, since binds Hb with 200x affinity versus O2 2. CO-Hb impairs O2 unloading (left-shifts Hb-O2 dissociation curve) by stabilizing R state 3. CO-Hb inhibits cytochrome oxidase in ETC, thereby preventing O2 consumption and ATP production
39
CO poisoning - Pathognomonic clinical finding
Cherry-red skin
40
CO poisoning - Early sign of exposure
Headache
41
CO poisoning - Treatment
100% O2 therapy
42
Factors causing a left-shifted Hb-O2 dissociation curve (6)
1. metHb 2. CO 3. HbF 4. Increased 2,3-BPG 5. Decreased temperature 6. Decreased H+ / increased pH / alkalosis
43
Anemia - PaO2 - SaO2 - Hb-O2 dissociation curve - Cytochrome oxidase
Anemia - PaO2 - NORMAL - SaO2 - NORMAL - Hb-O2 dissociation curve - NORMAL - Cytochrome oxidase - NORMAL
44
Methemoglobinemia - PaO2 - SaO2 - Hb-O2 dissociation curve - Cytochrome oxidase
Methemoglobinemia - PaO2 - NORMAL - SaO2 - DECREASED - Hb-O2 dissociation curve - LEFT-SHIFTED - Cytochrome oxidase - NORMAL
45
Carbon monoxide poisoning - PaO2 - SaO2 - Hb-O2 dissociation curve - Cytochrome oxidase
Carbon monoxide poisoning - PaO2 - NORMAL - SaO2 - DECREASED - Hb-O2 dissociation curve - LEFT-SHIFTED - Cytochrome oxidase - INHIBITED
46
Cyanide poisoning - PaO2 - SaO2 - Hb-O2 dissociation curve - Cytochrome oxidase
Cyanide poisoning - PaO2 - NORMAL - SaO2 - NORMAL - Hb-O2 dissociation curve - NORMAL - Cytochrome oxidase - INHIBITED Cyanide inhibits cytochrome oxidase (complex IV) in the electron transport chain, which prevents O2 consumption. Shutdown of the ETC prevents the diffusion from blood to tissue 2/2 loss of the diffusion gradient.
47
Hallmark of reversible cell injury
Cellular swelling with loss of microvilli and membrane blebbing
48
Reversible cell injury - Decreased ATP synthesis in the mitochondria 2/2 hypoxia causes (2)
1. Anaerobic glycolysis - Net gain of 2 ATP 2. Na-K ATPase dysfunction
49
Reversible cell injury - Anaerobic glycolysis causes (3)
1. Lactic acidosis 2. Low pH denatures structural/enzymatic proteins 3. Low pH precipitates DNA (chromatin clumping)
50
Reversible cell injury - Na-K ATPase dysfunction causes
Na+ and water to buildup in the cell --> Cellular swelling
51
Reversible cell injury - Swelling of the cytosol causes (2)
1. Loss of microvilli | 2. Membrane blebbing
52
Reversible cell injury - Swelling of the endoplasmic reticulum (ER) causes (2)
1. Dissociation of ribosomes, leading to decreased protein synthesis 2. Fatty change 2/2 decreased synthesis of apolipoproteins
53
Hallmark of irreversible cell injury
Membrane damage
54
Irreversible cell injury - Prolonged decreased ATP synthesis in the mitochondria 2/2 hypoxia causes
Ca2+ ATPase pump dysfunction, thereby increasing cytosolic [Ca2+]
55
Irreversible cell injury - Increased cytosolic [Ca2+] activates enzymes (4)
1. Phospholipase - Increases cell and organelle membrane permeability 2. Proteases - Damages cytoskeleton 3. Endonucleases - Degrades nuclear chromatin (karyolysis) 4. Caspases - Triggers apoptosis
56
Irreversible cell injury - Increased cytosolic [Ca2+] activates phospholipase, which damages cell and organelle membranes (4)
1. Plasma membrane 2. Inner mitochondrial membrane 3. Outer mitochondrial membrane 4. Lysosomal membrane
57
Irreversible cell injury - Consequences of mitochondrial membrane permeability/damage (3)
1. Cytochrome c in the ETC (inner mitochondrial membrane), is released into the cytosol, where it activates caspases, thereby triggering apoptosis 2. Pro-apoptotic proteins sequestered in the mitochondrial matrix (b/w inner and outer mitochondrial membranes) are released into the cytosol (activate apoptosis) 3. Mitochondrial conductance channels (pores) are opened, leading to loss of H+ ions and loss of the membrane potential, eliminating oxidative phosphorylation function
58
Hallmark of cell death
Loss of nucleus
59
Mechanism of nuclear loss (3)
1. Pyknosis (condensation) 2. Karyorrhexis (fragmentation) 3. Karyolysis (dissolution)
60
Cell death - Types (2)
Apoptosis and necrosis
61
Coagulative necrosis - Definition
Necrosis with preservation of the structural/architectural outline of dead cells
62
Coagulative necrosis - Mechanism (2)
1. Denaturation of enzymes and structural proteins | 2. Inactivation of intracellular enzymes, including lysosomal enzymes, prevents autophagy
63
Gross manifestation of coagulative necrosis
Infarction | - Exception is cerebral infarction
64
Pale (ischemic) infarction - Mechanism
Increased density of tissue prevents RBCs released from damaged vessels from diffusing through the necrotic tissue - Heart, kidney, spleen
65
Hemorrhagic (red) infarction - Mechanism
Loose-textured tissue allows RBCs released from damaged vessels to diffuse through the necrotic tissue - Lung, bowel, testicle
66
Liquefactive necrosis - Definition
Necrosis with degradation of tissue that softens and becomes liquified
67
Coagulative necrosis - Mechanism
Release of lysosomal enzymes by necrotic cells and/or the release of hydrolytic enzymes by neutrophils entering the tissue - Note that the release of lysosomal enzymes occurs prior to the denaturation of structural and enzymatic proteins, opposite that of coagulation necrosis
68
Gross manifestation of liquefactive necrosis (2)
1. Cerebral infarction - Autocatalytic effect of hydrolytic enzymes released by neuroglial cells 2. Bacterial abscess - Hydrolytic enzymes released by neutrophils liquefy dead tissue, producing a cavity filled with purulent material
69
Caseous necrosis - Infections (3)
1. Mycobacterium tuberculosis (TB) 2. Nocardia 3. Fungal infections
70
Caseous necrosis - Mechanism
Caseous material is produced by the release of lipid from the cell walls (mycolic acid) of M. tuberculosis, Nocardia, and systemic fungi after immune destruction by macrophages in the granulomas
71
Enzymatic fat necrosis - Pathologic condition - Mechanism
- Enzymatic fat necrosis of the peripancreatic fat 2/2 acute pancreatitis - Pancreatic lipase and phospholipase hydrolyze triacylglycerols in fat cells with release of fatty acids - Ca2+ combines with the fatty acids to produce soap (saponification --> dystrophic calcification)
72
Traumatic fat necrosis - Pathologic condition - Mechanism
- Non-enzymatic fat necrosis in fatty 2/2 blunt trauma or surgery (e.g., breast trauma) - Ca2+ combines with the fatty acids released 2/2 blunt trauma to produce soap (saponification --> dystrophic calcification)
73
Necrosis types a/w the pancreas (2)
1. Liquefactive necrosis of the pancreatic parenchyma | 2. Enzymatic fat necrosis of the peripancreatic fat
74
Dystrophic calcification
Abnormal deposition of Ca2+ in NONVIABLE TISSUES in the setting of NORMAL Ca2+/phosphate levels
75
Metastatic calcification
Abnormal deposition of Ca2+ in VIABLE TISSUES in the setting of ABNORMAL (ELEVATED) Ca2+ and/or phosphate - Elevated phosphate drives Ca2+ into tissues
76
Fibrinoid necrosis - Definition/mechanism
Deposition of pink-staining proteinaceous material (fibrin) in damaged tissue
77
Fibrinoid necrosis - Conditions (3)
1. Malignant hypertension 2. Immune vasculitis 3. Pre-eclampsia (fibrinoid necrosis of the placental vessels)
78
Free radicals - Targets (2)
1. Nucleic acids (oxidation of DNA) | 2. Cell membranes (lipid peroxidation)
79
Brown atrophy
Undigested lipids derived from lipid peroxidation of autophagized organelle membranes are stored as RESIDUAL BODIES (LIPOFUSCIN/LIPOCHROME) in PRIMARY LYSOSOMES - Brown/yellow "wear and tear" pigment
80
``` Reactive oxygen species (ROS): O2 + 1e = O2 + 2e = O2 + 3e = O2 + 4e = ```
O2 + 1e = superoxide (O2•-) O2 + 2e = hydrogen peroxide (H2O2) O2 + 3e = hydroxyl radical (OH•) O2 + 4e = 2H2O
81
Most destructive free radical
Hydroxyl radical (OH•)
82
Antioxidants (4)
Vitamin A, vitamin C, vitamin E, glutathione
83
Glutathione - Oxidized and reduced forms
Oxidized form - GSSG | Reduced form - 2GSH
84
Antioxidant that best neutralizes hydroxyl radical (OH•)
Vitamin C
85
Reactive oxygen species - Superoxide dismutase (SOD) - Cellular location - Catalyzed reaction
``` Superoxide dismutase (mitochondria) 4 O2•- + (4H+) --> 2H2O2 + 2O2 ```
86
Reactive oxygen species - Glutathione reductase - Cellular location - Catalyzed reaction
Glutathione reductase (mitochondria) 1. H2O2 (generated from SOD) is reduced to form 2H20 2. Reduced glutathione (2GSH) is oxidized to form oxidized glutathione (GSSG)
87
Reactive oxygen species - Catalase - Cellular location - Catalyzed reaction
Catalase (peroxisomes) | 2H2O2 --> 2H2O + O2
88
Acetaminophen - Metabolism in normal doses
CYP450 system - Smooth ER of hepatocytes | - Metabolized to glucuronate or sulfate conjugates that are excreted by the kidneys
89
Acetaminophen - Metabolism in toxic doses
CYP450 isoenzyme CYP2E1 - Smooth ER of hepatocytes | - Metabolized to toxic intermediate NAPQI
90
Acetaminophen - Metabolism in normal doses in alcoholics
- Alcohol induces CYP2E1 synthesis, causing a
91
Acetaminophen poisoning - Liver cell necrosis | - Initial site
Centrilobar zone III around the central venules | - Greatest concentration of CYP2E1 in zone III
92
Amyloidosis - Mechanism of injury
Amyloid deposits in interstitial tissue, which results in organ dysfunction 2/2 pressure atrophy of adjacent cells
93
Amyloidosis - Congo red stain with polarizing microscopy
Amyloid stains red with Congo red stain and exhibits apple green birefringence under polarizing microscopy 2/2 beta-pleated sheet configuration of misfolded proteins
94
Primary amyloidosis is the systemic deposition of ___ amyloid which is derived from ___
Primary amyloidosis is the systemic deposition of AL AMYLOID which is derived from Ig light chains synthesized in plasma cells
95
Primary amyloidosis a/w (1)
Plasma cell dyscrasias
96
Secondary amyloidosis is the systemic deposition of ___ amyloid which is derived from ___
Secondary amyloidosis is the systemic deposition of AA AMYLOID which is derived from SERUM AMYLOID A (SAA), an acute phase reactant synthesized by the liver
97
Secondary amyloidosis a/w (3)
1. Chronic inflammatory states 2. Malignancy 3. Familial Mediterranean fever
98
Familial Mediterranean fever - Inheritance - Pathology - Clinical findings (3)
FMF is an AR "auto-inflammatory" disorder characterized by excess IL-1 production a/w systemic AA amyloid deposition, fever, and inflammation of serosal surfaces (pleura, peritoneum, synovium)
99
Systemic amyloidosis - Organ most commonly targeted with amyloid deposition - Diagnosis
- Amyloid deposition most commonly in kidney - Diagnosis with abdominal fat pad or rectal biopsy - End-organ failure 2/2 amyloidosis must be transplanted
100
Senile cardiac amyloidosis - Amyloid protein - Amyloid protein derivation - Clinical findings
- Amyloid derived from TTR (ATTR) - Transthyretin (TTR) - T4 and retinoic acid carrier protein - Usually asymptomatic; present in 25% of patients > 80y/o
101
Familial amyloid cardiomyopathy - Amyloid protein - Amyloid protein derivation - Clinical findings
- Amyloid derived from mutated TTR (ATTR) - Mutated transthyretin (TTR) - Restrictive cardiomyopathy
102
Type II diabetes mellitus - Amyloid protein - Amyloid protein derivation
- Amyloid derived from islet amyloid polypeptide (AIAPP) - Islet amyloid polypeptide (IAPP), also called amylin - IAPP/amylin co-secreted with insulin
103
Alzheimer disease - Amyloid protein - Amyloid protein derivation
- Aβ amyloid | - β-amyloid precursor protein (β-APP), chromosome 21
104
Dialysis-associated amyloidosis - Amyloid protein - Amyloid protein derivation - Clinical findings
- Amyloid derived from β2M (Aβ2M) - β2-microglobulin (MHC class I light chain) - Amyloid deposition in joints, synovial membranes, and tendon sheaths --> Carpal tunnel syndrome, joint pathology
105
Medullary carcinoma of the thyroid - Amyloid protein - Amyloid protein derivation - Clinical findings
- Amyloid derived from calcitonin (A-Cal) - Calcitonin produced by neoplastic parafollicular C cells of the thyroid - Tumor in an amyloid background

*USMLE Step 1, General Principles (3 decks)

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