cell injury

What are the 3 categories of tissues based on proliferative capacity?

1. continuously dividing

2. stable

3. permanent

what are examples of continuously dividing tissues?(6)

1. skin

2. oral cavity

3. vagina

4. cervix

5. exocrine ducts

6. GI tract

what are stable cells?

cells that can divide in response to injury

examples of stable cells/tissues? (4)

1. endothelial cells

2. fibroblasts

3. smooth muscle

4. solid organs (liver, kidney, pancreas)

what are permanent cells?

cells with no proliferation after birth

examples of permanent cells

neurons

cardiac muscle

skeletal muscle

what can happen when a cell experiences stress or injury?

adaptation or

cell injury (resulting in cell death)

what are endogenous causes of cellular stress/injury?

hypoxia,

immunologic/autoimmune rxns,

genetic abnormalities,

aging

what are exogenous causes of cellular stress / injury? (4)

toxins (smoke, pollutants)

infectious pathogens

nutritional imbalance

physical agents (trauma)

what are the 4 major cellular adaptations to stress?

Hypertrophy

hyperplasia

atrophy

metaplasia

what is hypertrophy

increase in size of cell (increase size of organ)

hypertrophy usually occurs in what type of cells?

cells w limited capacity to divide

physiological example of hypertrophy

uterine enlargement during pregnancy

pathological example of hypertrophy?

cardiac enlargement secondary to hypertension

what is hyperplasia?

increase in number of cells

hyperplasia occurs in what type of tissue?

tissues capable of cell division

what are the two physiologic forms of hyperplasia?

hormonal (breast development)

compensatory (liver regeneration)

what commonly causes pathologic hyperplasia?

excessive hormonal or growth factor stimulation

examples of pathologic hyperplasia?

endometrial hyperplasia

benign prostatic hyperplasia

is hyperplasia the same as neoplasia(cancer)?

no hyperplasia is a controlled process

what is atrophy

decrease size of cells

what causes the loss of cell substance in atrophy?

decrease in protein synthesis and increased protein degradation

What are the 5 main causes of Atrophy?

1. decreased workload (ex use muscle less → become smaller)

2. diminished blood supply

3. inadequate nutrition

4. loss of endocrine stimulation

5. aging

what is metaplasia?

one cell type is replaced by another cell type

why does metaplasia occur?

adaptation allows new cell type to better withstand stress

classic example of metaplasia

in smokers ciliated columnar epithelium → stratified squamous epithelium in the trachea/bronchi

why is metaplasia clinically important?

it may predispose to malignant transformation

what is dysplasia?

disordered cellular growth involving proliferation of precancerous cells

is dysplasia necessarily cancer?

No. it may be reversible but may progress to cancer

what is aplasia?

failure of cell production during embryogenesis → missing structure

what is hypoplasia?

decrease in cell production during embryogenesis → relatively small structure

When does cell injury occur?

When stress exceeds the cells adaptive ability

what determines the extent of cell injury? (3)

• type of injury

• duration

• type of cell

name the 5 types of cell injury

1. Hypoxia/ischemia

2. oxidative stress

3. toxins

4. DNA damage

5. inflammation

how long can neurons tolerate ischemia without irreversible injury?

3-5 mins

how long can myocardial cells tolerate ischemia without irreversible injury?

1-2 hours

how long can skeletal muscle tolerate ischemia w out irreversible damage

hours

what is hypoxia

oxygen deficiency

what is ischemia?

reduced blood supply → oxygen def

blockage of an artery is an example of what?

ischemia

how can hypoxia cause cell death?

decreased o2 → failure of metabolic pathways →necrosis

Why do metabolic pathways fail in the absence of oxygen?

ATP production requires oxygen and cellular metabolism requires ATP

what are some example diseases that may cause hypoxia?

lung disease and anemia

where do ROS come from?

small amount from respiration and energy generation

mostly produced in phagocytic leukocytes (neutrophils and macrophages)

when do ROS accumulate? (3)

1. absorption of radiant energy (UV, x-ray)

2. metabolism of exogenous chemicals (ex drugs )

3. inflammation

2 mechanisms to minimize injury from reactive oxygen species?

1. free radical scavengers

2. antioxidants

what are 3 free radical scavengers that minimize injury from ROS ?

1. superoxide dismutase

2. glutathione peroxidase

3. catalase

name the 2 ways antioxidants work to protect cells from oxidative stress

1. block formation of free radicals

2. scavenge after they have been formed

examples of antioxidants

vitamin A,E,C and β-carotene (exogenous)

True or False: Antioxidants can be endogenous or exogenous

true

what are 3 mechanisms of how ROS cause injury to cell

1. membrane damage

2. protein crosslinking (misfolding)

3. DNA damage

what is reversible cell injury?

normal function and morphology can return when stimulus is removed

most common change in reversible cell injury?

swelling

what is irreversible cell injury?

cells cannot recover and will die

what are 3 main causes of irreversible cell injury?

1. inability to restore mitochondrial fntn

2. loss of structure/ fntn of plasma membrane and intracellular membrane

3. loss of DNA and chromatin structural integrity

pyknosis

nuclear condensation

(irreversible shrinking and condensation of nucelus)

karyorrhexis

fragmentation

karyolysis

dissolution- nucleus just fades away

what are the 2 mechanisms of cell death?

apoptosis

necrosis

what happens to the cell membrane in necrosis

membrane falls apart

what happens after the membrane falls apart in necrosis?

enzymes leak out and digest the cell

what major tissue response does necrosis cause?

inflammation

name all the 6 patterns of necrosis

1. coagulative

2. liquefactive

3. gangrenous

4. caseous

5. fat

6. fibrinoid

what pattern of necrosis causes infarction of a solid organ?

coagulative

what organ is the major exception to coagulative necrosis after hypoxia?

brain

gross appearance of coagulative necrosis

tissue appears firm

what happens to cell outlines in coagulative necrosis

they remain preserved

nuclear appearance in coagulative necrosis

no nucleus

H&E color coagulative necrosis

pink

what pattern of necrosis is caused by bacteria/ fungal infections?

liquefactive necrosis

hypoxia in the CNS (brain) causes what pattern of necrosis

liquefactive necrosis

gross appearance of liquefactive necrosis

dissolution of tissue into viscous liquid

ischemia of a limb causes what pattern of necrosis

gangrenous necrosis

what is the underlying pattern in gangrenous necrosis?

coagulative necrosis

what does gangrenous necrosis resemble grossly?

mummified tissue (coagulative necrosis)

what can become superimposed on gangernous necrosis

liquefactive necrosis

What might cause ischemia of a limb, leading to gangrenous necrosis

uncontrolled diabetes

what pattern of necrosis is cause by tuberculosis?

caseous

gross appearance of caseous necrosis

cheese like, friable (flakey) yellow white tissue

histological hallmark of caseous necrosis

caseating granulomas

what is a granuloma

group of macrophages

what is a caseating granuloma

a granuloma w central necrosis

what pattern of necrosis is caused by pancreatitis

fat necrosis

what enzyme initiates fat necrosis?

lipase

what accumulates after fat-cell breakdown?

calcium

gross appearance of fat necrosis

chalky white deposits in fat

histological appearance of fat necrosis

outlines of dead fat cells w no nuclei

fibrinoid necrosis occurs where

blood vessels

what 2 conditions are associated w fibrinoid necrosis

1. immune-mediated conditions

2. hypertension

histopathological features of fibrinoid necrosis

eosinophilic deposits in wall of bv

Pyknosis → karyorrhexis → karyolysis means?

Condensation → fragmentation → dissolution.

what happens to nucleus during apoptosis

condenses and shrinks

what structures form from the dying cell by apoptosis

apoptotic bodies

who removes apoptotic bodies

macrophages

does apoptosis cause inflammation?

no! necrosis does tho