Chapter 1 Flashcards
Pathology is the study of ______
disease (suffering)
Etiology is defined as:
Origin of disease (why)
Pathogenesis is defined as:
Steps in development (how)
What are the 4 types of cellular adaptations to stress
Hypertrophy
Hyperplasia
Atrophy
Metaplasia
Define Hypertrophy
Increase size of cells/organ, with no new cells
cells are incapable of replication
Define Hyperplasia
increase number of cells
cells must be able to replicate
Defne Atrophy
Reduction in cell/organ size
decreased protein synthesis
increased protein breakdown
decreases overall function but not dead!
Denervation and ischemia to a muscle will cause _______
atrophy
Features of cerebral atrophy
narrowed gyri
widened sulci
Causes of cerebral atrophy
atherosclerosis (ischemia)
alzheimer disease
cerebral palsy
malnutrition
Define Metaplasia
reversible replacement of 1 mature (differentiated) cell type by another
more resilient cell type
What is a common cause of metaplasia
adaptation to prolonged stressors like chronic irritation from smoking or GERD
2 consequences of metaplasia
altered structure can decrease function
risk for malignant transformation
injury occurs once stressors…
exceed a cells ability to adapt
directly induce abnormalities
2 types of injury
reversible and irreversible
3 steps of necrosis
Karyolysis, pyknosis and karyorrhexis
5 general types of necrosis
coagulative, liquifactive, caseous, fat, and fibrinoid
Coagulative Necrosis is caused by…
ischemia (aka, ischemic necrosis)
Define solid organ infarction
phenomenon that occurs when coagulative necrosis occurs in a solid organ like a kidney.
tissue structure is preserved due to the denaturation of proteolytic enzymes, which lasts for a few days-weeks
Gangrenous necrosis
coagulative necrosis in an extremity
commonly caused by peripheral vascular disease (diabetes, atherosclerosis)
dry, wet, gas –> all equally gross
Liquifactive necrosis
dead cells get completely digested
WBC enzymes produce a liquid viscous mass
eventual phagocytosis
2 instances of liquifactive necrosis
infections (bacterial: pus and abscess; fungal)
CNS ischemia/Hypoxia
Caseous Necrosis
“cheese-like” appearance: friable
ENCLOSED WITHIN A DISTINCTIVE BORDER
Most common cause of Caseous Necrosis
Tuberculosis (TB)
“caseating granuloma”
Granuloma is defined as…
walled-off collection of macrophages
Fat necrosis
localized fat destruction
2 causes for fat necrosis
acute pancreatitis: leaked pancreatic enzymes which cause fat saponification
trauma to breast
Fibrinoid Necrosis
Caused by autoimmune reactions in which immune complexes + fibrin are deposited into arterial walls
Requires histological evaluation
Examples of conditions that cause Fibrinoid Necrosis
Polyarteritis Nodosa
Systemic Lupus Erythmatosus
Malignant Hypertension
Transplant Rejections
Apoptosis
Programmed/regulated cell death
caused by enzymatic breakdown
intact membranes –> no inflammation
Mitochondrial (Instrinsic) Pathway of Caspase Activation
Decrease GF, DNA damage, Misfolded proteins
Increased mitochondrial membrane permiability
Utilizes Caspase 9
Death Receptor (Extrinsic) Pathway of Caspase Activation
Binding with surface molecules “death receptors”
eliminates self-reactive lymphocytes or virus infected cells
utilizes Caspase 8
What is autophagy
Lysosomal digestion of a cell’s components
Depletion of ATP as a mechanism of cellular injury
hypoxia, nutritional deficiency, mitochondrial damage, toxins
decrease oxidative phosphorylation (glycolytic capacity in liver and brain)
ATP-dependent pumps (increase Na and Ca) Glycolysis (decrease pH)
Mitochondrial damage as a mechanism of cellular injury
Hypoxia, toxins, irradiation
disrupted membranes –> necrosis
increased ROS production –> Apoptosis
influx of calcium as a mechanism of cellular injury
ischemia and toxins
activates enzymes –> apoptosis
Oxidative stress as a mechanism of cellular injury
ischemia-reprofusion, toxins, irradiation, cellular aging (redox), inflammation (macrophages and neutrophils)
accumulation of ROS –> apoptosis
Defects in membrane permiability as a mechanism of cellular injury
ischemia, toxins, physical trauma, complement activation
phospholipids: decrease production & increase breakdown
involves many important membranes (mitochondrial, planma, lysosome)
hallmark of tissue necrosis
DNA and protein damage as a mechanism of cellular injury
severe oxidative stress, irradiation, abnormal protein folding
severe/irreparable damage
stimulates apoptosis
Ischemia and hypoxic injury impacts aerobic and anaerobic metabolism
aerobic: mitochondrial damage (decrease ATP, Increase ROS
anaerobic: decrease glycolysis substrates, increase waste
ischemia and hypoxic injuries are reversible, true or false?
True, if blood supply and oxygen are restored in a timely manner
Persistent ischemia
irreversible injury
ruptured membranes
necrosis and minimal apoptosis
Ischemia reprofusion injury
temporary ischemia where restoration of blood flow causes inflammation which increases ROS
Direct chemical injury
combination with cellular organelles
cells that absorb, use, excrete or store a toxin
inhibits use of ATP or damages membranes
Indirect chemical injury
biologic conversion produces a reactive metabolite
Intracellular accumulations are caused by (4)
Abnormal metabolism (fatty liver disease)
Defective protein folding/transport (mutations)
Defective or absent enzymes
Ingestion of indigestible materials (silica, asbestos, coal dust)
Fatty change (steatosis)
abnormal accumulation of lipids within tissue parenchyma
triglycerides are common intracellular inclusions
Alcoholic liver disease and non-alcoholic liver disease
2 types of pathologic calcification
dystropic calcification
metastatic calcification
dystropic calcification
accumulation of Ca within damaged tissue
traumatized cells and necrotic cells
normal Ca metabolism
Fibrodysplasia ossificans progressiva
dysfunctional soft tissue repair any trauma --> heterotopic ossification joint ankylosis (fusion) severe deformation and dysfunction
Metastatic calcification
accumulation of Ca within normal tissues
caused by abnormal Ca homeostasis (hypercalcemia)
may deposit into any tissue
most common are vessels, kidneys, lungs, GI tract
Cellular aging
reduced functional capacity of cells caused by accumulation of cellular/molecular damage
3 causes of cellular aging
DNA damage: accelerated by ROS
Replicative senescence: shortened telomeres –> no more mitosis
defective protein homeostasis: decreased synthesis, increased turnover, more misfolding
Progeroid syndromes
accelerated aging
progeroid syndrome in teens
Bloom Syndrome
Progeroid syndrome in adults (40s)
Werner Syndrome
Karyolysis
Nuclear fading - chromatin dissolution due to action of DNAases and RNAases
Pyknosis
Nuclear shrinkage - DNA condenses into shrunken basophilic mass
Karyorrhexis
Nuclear fragmentation - pyknotic nuclei membrane ruptures & nucleus undergoes fragmentation
myocardium subjected to persistent increased load, as in hypertension or with narrowed (stenotic) valve, adapts by undergoing…
hypertrophy
pathologic adaptations are…
responses to stress that allow cells to modulate their strucure and function and thus escape injury
metaplasia is thought to arise by…
reprogramming of stem cells to differentiate along a new pathway rather than a phenotypic change
hypoxia
oxygen deficiency
ischemia
loss of blood supply
lipfuscin
wear and tear pigment that can accumulate in a variety of tissue as a function of age or atrophy
