6_Cell Adaptation

Question 1

what are the cellular responses to injuries?

Answer 1

• may be reversible or irreversible
  
  1. alterations in size
  2. alterations in differentiation
  3. proliferation
  4. programmed cell death (apoptosis)

Question 2

modes of cellular adaptation:

increases and processes

Answer 2

• Increases:
  
  • Regeneration –> replacement of losses by cellular multiplication
  • Hyperplasia –> increase in cell number above normal
  • Hypertrophy –> increase in cell size above normal

Question 3

modes of cellular adaptation:

decreases and processes

Answer 3

Decreases

• Hypoplasia –> decrease in cell NUMBER below normal
• Atrophy –> decrease in cell SIZE below normal
• Involution –> loss of cellular content of organs (usually by apoptosis)

Question 4

modes of cellular adaptation:

changes and processes

Answer 4

Changes

• Modulation –> reversible modification of phenotype
• Metaplasia –> replacement of cells by a diff’t type of cell
• Neoplasia –> transformation into a cancer cell
• Subcellular adaptations –> adaptation of intracellular organelles

Question 5

hypertrophy:

causes, and examples

Answer 5

• Inc. functional demand - myocardial hypertrophy from HTN or aortic stenosis
• Endocrine stimulation of hormones - pituitary hormones; menstrual cycle
• Local mitogens - macrophage response
• Inc. nutrition - muscle and adipose hypertrophy from extra calories
• Inc. Blood Flow - asymmetrical limb growth following unilateral AV fistula
• Mechanical factors - skin after traction
• Pharm agents - salivary gland following isoproterenol
• Imbalance b/w anabolism/catabolism - bone (osteoporosis, osteopetrosis)

Question 6

Hyperplasia:

define, mech, ex

Answer 6

• def: increased cell number
  
  • can increase size and functional capacity in affected organ
  • can be accompanied by cellular hypertrophy
• mech: results from stimulation of target tissues by hormones or growth factors
  
  • if prolonged – can be precursor of cancer (unopposed estrogen stim of endometrium)
  • can be response to homeostatic disturbance; parathyroid secondary hyperplasia following hypocalcemia
• ex: regeneration of liver following partial hepatectomy

Question 7

primary hyperparathyroidism:

define

Answer 7

• sporadic/ component of MEN syndrome
• all four glands or asymmetric involvement w/ sparing of 1-2 glands
• combined weight rarely exceeds 1.0gm
• fat is inconspicuous

Question 8

graves disease:

define, histology, untreated cases

Answer 8

• def: autoimmune disorder that causes hyperthyroidism, or overactive thyroid
• histo: symmetrical diffuse hyperplasia of thyroid gland; soft meaty cut surface
• untreated:
  
  • tall, follicular epithelial cells forming papillae that encroach on colloid;
  • pale colloid w/ scalloped margins

Question 9

goiter:

define, assoc. w/ which drug

Answer 9

• enlargement of the thyroid; asymmetrically enlarged glands (colloid-rich follicles w/ areas of follicular hyperplasia)
  
  • manifestation of thyroid disease
  • degree of thyroid enlargement is proportional to the level and duration of thyroid hormone deficiency
• pathogenesis
  
  • impaired synthesis of thyroid hormone; compensatory rise in the serum TSH level
    
    • hypertrophy and hyperplasia of thyroid follicular cells to ensue a euthyroid metabolic state
  • in case, the compensatory responses are inadequate the result is goitrous hypothyroidism

Question 10

atrophy:

characteristics, fxn, example

Answer 10

• atropy: decreased cell size, can be due to hunger, pressure of follicular adenoma
• fxn: diminished functional capacity w/o cell death;
  
  • can decrease size and capacity of affected organ
• ex:
  
  • striated muscle atrophy following denervation;
  • immobilization or decreased work load;
  • cardiac myocytes in severe coronary artery disease

Question 11

involution:

define, mechanism, cause, result

Answer 11

• def: decrease in cell number
• mechanism: apoptosis (e.g. cell suicide)
• cause:
  
  • common in hormone withdrawal; or can occur in development
  • breast or endometrium during menstrual cycle or postmenopausal
  • changes in thyroid and adrenal cortex w/ hypopituitarism
• result
  
  • in decreased size and functional capacity of affected organ

Question 12

metaplasia:

define, deficiency, example

Answer 12

• def: replacement of one type of differentiated cell by another derived from the same germ layer
  
  • change in gene expression in epithelial stem cells, or undifferentiated mesenchymal cells
• deficiency: loss of protection conferred by mucuous secretions and ciliary removal of particulate matter
• example:
  
  • squamous metaplasia of resp. tract lining in smokers;
  • better able to survive than normal mucosa
  • inc. risk of cancer

Question 13

metaplasia of:

• cervix
• intestinal

Answer 13

• cervix:
  
  • Squamous metaplasia of cervix uteri after infection by papilloma viruses
• intestinal:
  
  • intestinal metaplasia: replacement of esophageal squamous mucosa by columnar epithelium;
  • “barrett’s esophagus” w/ inc. risk of cancer development

Question 14

tissue repair from injury:

two processes

Answer 14

• regeneration: dependent on proliferative capacity
• connective tissue formation: (avascular tissue; “scar”)

Question 15

what are the 3 states of proliferative capacity of cells?;

how are they different?

Answer 15

• permanent: non-proliferative, terminally differentiated;
  
  • e.g. neurons, myocardial cells
• stable: quiescent, G0 phase of cell cycle; but capable of divsion;
  
  • e.g. hepatic, renal tubular, and pancreatic parenchymal cells, fibroblasts, smooth muscle cells, and endothelim
• labile: continuously dividing, both stem and mature cells; ex.
  
  1. bone marrow hematopoeitic cells
  2. most surface epithelia: squamous (skin, cervix, vagina, oral cavity)
  3. columnar epithelia: G-I tract, fallopian tubes, uterus
  4. transitional epithelia of urinary tract

Question 16

regeneration:

define, mech, ex

Answer 16

• def: the ability to regenerate tissue from stem cells; following damage
• mech: driven by cytokines, growth factors, and by cellular interactions w/ extracellular matrix
• ex: regeneration of liver following 90% hepatectomy
  
  1. proliferation of both hepatocytes and progenitor oval cells in the canals of herring
  2. mediated by cytokines and growth factors (i.e. EGF and HGF)
  3. hepatocyte proliferation followd by Kuppfer, stellate, adn endothelial cells
  4. dependent on structural integrity of liver; cirrhosis ensues in absence

Question 17

types of cell death:

and description

Answer 17

• necrosis: features involve denaturation of cell proteins w/ enzymatic digestion of the cell
• apoptosis: cell suicide involv. activation of caspases (proteases) that digest cell proteins;
  
  • fragmentation of the cell into apoptotic bodies that are phagocytosed
• necroptosis (programmed necrosis): common features of both necrosis and apoptosis w/o caspase activation
• pyroptosis: cell suicide accompanied by fever-inducing IL-1

Question 18

karyolysis; chromatolysis:

define

Answer 18

disappearance of chromatin substance and nuclear membrane w/ retention of cellular shape

(cell death terminology)

Question 19

karyorrhexis:

(define)

Answer 19

• breakage of the nucleus into small fragments

(cell death terminology)

Question 20

pyknosis:

define

Answer 20

condensation of the nuclear material into small, deeply staining fragments

(cell death terminology)

Question 21

cell death term –> usage:

• cell death
• necrosis
• oncotic necrosis
• apoptosis

Answer 21

• cell death –> irreversible loss of cell functions;
  
  • not detectable morphologically
• necrosis –> morphologic changes following cell death
• oncotic necrosis –> necrosis en masse; cell swelling, pyknosis, karyolysis
• apoptosis –> individual cells; pyknosis, karyloysis, cell shrinkage, and fragmentation

Question 22

cell necrosis:

what are the morphological changes assoc. w/ necrosis?

Answer 22

• necrotic changes: assoc. w/ dead cells in living tissue; differ from post-mortem auto-lysis
• nuclear changes:
  
  1. fading of stainable chromatin (Karyolysis)
  2. nuclear condensation (Pyknosis), and /or fragmentation (karyorrhexis)
• cytoplasmic changes:
  
  1. protein denaturation w/ maintenance of cell outlines (coagulative necrosis)
  2. enzymic digestion of dead cells (liquifactive necrosis)

Question 23

what are the 4 morphological variants of necrosis:

Answer 23

• coagulative necrosis: typical in cell death resulting from ischemia/hypoxia
  
  • parenchymal infarction;
  • e.g. acute renal infarct
• liquefactive necrosis: typical of CNS infarctions and bacterial infarctions
• caseous necrosis: cheesy macroscopic appearance of necrotic tissues; most often assoc. w/ mycobacterium tuberculosis
  
  • e.g. pulmonary tuberculosis
• fat necrosis: liquefactive necrosis of adipose tissue adjacent to injured exocrine glands; seen in acute pancreatitis
  
  • e.g. acute pancreatitis

Question 24

gangrene:

define, and two types

Answer 24

• def: infarction of exremities
• types
  
  • dry gangrene: sterile, predominantly coagulative necrosis
  • wet gangrene: secondarily infection, w/ liquefactive necrosis

Question 25

apoptosis:

define, modulating factors

Answer 25

• define: form of cell death usually distinct from necrosis in causes, mechanisms, and consequences
• modulating factors:
  
  • mediated by activation of a series of events effected by a number of gene products

Question 26

how is apoptosis different from necrosis?

Answer 26

• Necrosis: outside factors kill the cell;\
  
  • ALWAYS anormal/pathological
• Apoptosis: the cell kills itself;
  
  • sometimes normal/physiological
  • sometimes normal in development

Question 27

what are the differences b/w these types of cell death?

• excitotoxicity
• DNA damage
• necroptosis

Answer 27

• excitotoxicity - death of neurons in response to high brain glutamate levels following stroke
• DNA damage - PARP (poly-ADP)-ribose polymerase caused overconsumption of vital NADH
• necroptosis - necrosis induced by the tumor necrosis factor receptor (TNF) which usually induces apoptosis