Cell Injury

How does the heart enlarge? Cardiac muscle cells do not divide

cells need to enlarge: synthesize more cellular or cytosolic components

hypertrophy definition

increase in cell size

mechanism of hypertrophy (mechanical and trophic triggers)

stressor → stretch of myocytes or release of growth factors or hormones → signaling pathway to proteins

physiological vs pathological hypertrophy

physiological: stronger heart (good for you), during exercise

pathological: cell injury and progression to heart failure, 24/7

pathological hypertrophy

trying to make heart feel stronger, fetal gene expression

Hyperplasia definition

increase in cell number

what is required for hyperplasia

cells capable of dividing: less differentiated stem cells, differentiated cells

What two main ways cause physiologic hyperplasia?

Hormonal, compensatory

skeletal muscles can/cannot divide

smooth muscle can/cannot divide

skeletal cannot, smooth can

atrophy definition

shrinkage of cells from loss of substances

atrophy causes (3)

loss of stimulation (hormonal or nervous), inadequate blood supply, inadequate nutrients

main cause of ginigval hyperplasia

drug induced

what is autophagy? End result?

self eating, end result digest cellular components which provides nutrients for cell

why do cells atrophy?

small size enables survival

what 3 things integrate in autophage for nutrient breakdown?

sER membrane, autophagic vacuole, lysosome

metaplasia definition

switch from one cell type to another

metaplasia cancer relationship

metaplasia increases risk of cancer

3 ways of hypoxia

ischemia (reduced blood supply), reduced O2 carrying capacity, reduced oxygenation

two morphological pattern with reversible injury:

swelling, fatty changes (seen more often in liver)

when does cell swelling occur? what happens?

damage to plasma membrane or decrease in intracellular ATP

increase in ions (esp sodium), brings in more water

5 typical changes with reversible cell injury in swelling

1. blebls/loss of microvilli

2. ER swelling (vacuoles)

3. Mitochondria swelling

4. ribosome detachment (protein synthesis decreases)

5. nuclear chromatin clumping

gross changes with reversible cellular injury (swelling)

increased weight and turgor

increased pallor (compression of capillaries)

cellular changes with necrosis (4) (and consequences)

1. damaged lysosomal membrane (ROS + enzymes leaks out) → digest organelles

2. DNA damaged

3. damaged plasma membrane (cell contents leaks out, cell fragments)

4. mitochondrial damage (deplete ATP and generate ROS)

what happened?

necrosis

How does body respond to necrosis?

release of cellular contents → initiates inflammation

DNA condenses: becomes solid, shrunken, dark mass

pyknosis

pynkotic nucleus fragments

karyorrhexis

DNAase activation → DNA dissolution

karyolysis

label each from left to right

karyorrhexis, pynkosis, karyolysis

coagulative necrosis often occurs in __ _?

solid organs (kidney)

main cause of coagulative necrosis

ischemia (loss of blood supply)

Coagulative necrosis color, texture, shape?

pale (no blood), firm (tissues not degraded), wedge shape

liquefactive necrosis main cause

focal bacterial or fungal infection → pus/proleytic enzymes that destroy surrounding tissue

an abscess is indicative of what tissue necrosis?

liquefactive necrosis

Abscess and pus definitions

accumulation of pus (liquified necrotic tissue), in enclosed space

In brain, what is the cause of liquefactive necrosis?

from ischemia (NOT infection)

what does the brain have a ton of compared to other organs such as kidney or heart?

lipids

End result of liqueatative necrosis (unique too)

dead tissue is removed → cavity or cystic space

gangrenous necrosis cause

insufficient blood to limbs (esp toes) → multiple tissue layers die and undergo coagulative necrosis → gangrene

two situations where person may get gangrene

chronic diseases: poor circulation (diabetes)

trauma or physical injury (forstbite)

wet vs dry gangrene

dry: reduced blood flow: coagulative necrosis

wet: reduce blood flow plus bacterial infection: coagulative → liquefactive necrosis

caseous necrosis: a main cause?

tuberculosis: necrotic core of granuloma → necrotic cells not completely digested (caseous “cheese like”)

caseous necorsis is due to?

body trying to wall off and kill bug with macrophages

focal areas of fat destruction

fat necrosis

fat necrosis causes (2)

trauma to fatty tissue

damage to fat from pancreatitis (inflammation of pancreas: more common)

how does pancreatitis cause fat necrosis: what layer? What cells?

triglycerides from fat cells in mesentery around pancreas → lipase leaks out from damaged pancreatic acinar cells → fatty acids + calcium = saponification

where is there another form of cell death besides necrosis

want to eliminate without inflammation

apoptosis occurs during __ conditions

physiological and pathological

fetal development: embryogenesis: apopotosis: pathological or physioogical?

physiological: get ride of webbing (loss of growth factors)

another purpose of apoptosis

eliminate irreparably damaged cells

Whats similar in mitochondrial and death receptor pathway

Executioner caspase (caspase 3) cleaves proteins → activate enzymes that degrade DNA and proteins, including nuclear matrix and cytoskeleton

morphological appearance of apoptosis

cells shrunken: potassium channels open

nuclei dark and fragmented

growth factor withdrawl, DNA damage, proteins misfolding: what pathway?

mitochondrial

activate death receptors (fas or TNF receptor) pathway

death receptor pathway

death receptor pathways receptors (2)

Fas or TNF

When does blebbing occur? what is the difference?

both in apoptosis and reversible, but they pinch off in apoptosis

apoptosis: shrunken cell, chromatin, condensation

pyknosis

apoptosis: DNA fragmentation

karyorrhexis

what happens to apoptotic bodies? What is the signal for phagocytosis? why?

phosphatidylserine (PS) flips from inner to outer leaflet of plasma membrane, this does NOT cause inflammation

fill it in

• enlarged (swelling), reduced (shrinkage)

• Pynkosis → karyorrhexis → karyolysis, fragmentation into nueclosome size fragements

• Disrupted, intact: (altered structure, esp orientation of lipids)

• Enzymatic digestion (can leak out), intact (may be apoptotic bodies)

• Frequent, no

• Invariably pathologic (culmination of irreversible cell injury), often physiologic, can be pathological (esp DNA and protein damage)

what 3 things does if injuries are irreversible or reversible depend on?

severity, duration, type/status of cell (type, genetics, nutritional status/previous injury)

sometimes necrosis, sometimes apoptosis, why?

depends on type of injury

hypoxia and ischemia causes what? why?

depletion of ATP, cant aerobic

what is hypoxia/ischemia? What does it do to accomodate? (1 thing to cause 3)

lack of O2 → less ATP from oxidative phosphorylation

Activates hypoxia inducible factor 1

• increase glycolysis

• increase glucose uptake

• increase glycogenolysis

Whats more resistant to ischemia or hypoxic?

Liver and skeletal muscle: have more glycogen

What happens to intracellular pH with hypoxia?

more acidic (lower pH) → can inhibit enzyme activity, clumping of chromatin in nucleusi

is hypoxia/ischemia effects (decrease ATP, use glycogen stores, increase glycolysis and lactic acid production) reversible or irreversible?

usually reversible

How does lack of ATP affect cell: why?

• protein synthesis:

• Cell size:

• ER size:

• Ribosomes:

more Na+ (less K+), increased solute concentration

• decreases

• swells

• dilates

• detach

ischemia effect on cell? (lack of ATP)

impairs activity of Ca++ pump (main signalign pathway) and intracellular Ca2++ rises

How does incrase in intracellular Ca++ contribute to injury? (4)

uncontrolled activation of many cellular enzymes

• phospholipase

• Protease (degrade enzymes)

• Endonuclease

• ATPase (help deplete ATP)

How does Ca affect the cytoskeleton?

damages it, detaches from plasma, surge of cytoplasm into area

What helps cause the plasma/organelle membrane and DNA damage with necrosis?

large increase in cytosolic Ca → Ca induced activation of phospholipases, proteases, endonucleases

what are ROS

type of free radical that contains oxygen: (has single unpaired electron in outer orbit)

IF ROS is out of balance ?

oxidative stress

what 3 things can increase ROS and cause oxidative stress>

infection (inflammatory cells that destroy microbes generate ROS), ionizing radiation and some chemicals, ischemia reperfusion injury

How does ROS cause cell injury (3) and conseuqnces of each

1. lipid peroxidation → damages membranes (reversible then necrosis)

2. single stranded DNA breaks (apoptosis)

3. cross-link or fragment proteins (necrosis, apoptosis)

food oxidants, inlammatory products, cigarette smoke, dental material residues → ? associated with what?

oxidative stress in oral cavity, associated with periodontal disease

When is it irreversible (necrosis)?

mitochondrial damage, plasma and lysosomal membrane damage, fragmentation of DNA and chromatin