Pathophysiology slides 2

cell structures and functions

plasma membrane

nucleus

mitochondrion

endoplasmic reticulum and ribosomes

Golgi apparatus

lysosomes

plasma membrane

transportation nutrients and waste products

generate membrane potentials

cell recognition and communication

growth regulation

sensor of signals that enable cell to respond and adapt to changes in environment

nucleus

genetic info, recipe block

largest cytoplasmic organelle

contains genetic information DNA

mitochondrion

powerhouse for cell mechanics

energy, ATP (longterm energy)

convert energy to forms that can be used to drive cellular reactions

endoplasmic reticulum and ribosomes

lipids, proteins, create building blocks

Golgi apparatus

processing for transport

package and send off mail room for proteins and lipids

lysosomes

enzyme, break things down

digestion, final products of lysosomal digestion include amino acids, fatty acids, sugars

mitochondria and cellular metabolism

mitochondria play central role in cellular energetics and cell death signaling

ATP production via oxidative phosphorylation

requires O2

drives active transport pumps (Na-K or Na-Ca2)

reactive oxygen species: normal product of cellular metabolism in mitochondria

without O2

anaerobic metabolism, not as much ATP, by product: lactic acid buildup

aerobic: O2 present

liver cells

most organelles have similar structures except some with specialities

liver cells sensitive to increase in EPI levels → activate glycogenolysis (release glucose) → increase blood glucose for energy to fight or flee

adrenal and muscle cells

specialized

adrenal cortex cells detect ACTH → produce and secrete cortisol → muscle cells increase protein catabolism → increase amino acids to fuel resistance and/or adaptation process

which organelle has primary function of protein sythesis

ribosomes

cell injury: extrinsic

source is external, outside the cell or body

environment

stress

exposure to toxins

mechanical trauma

cell injury: intrinsic

natural changes

source is internal

genetics

hormonal changes/imbalances

immune malfunction

structural defects

contributors to cell injury: toxic

intrinsic, genetic

extrinsic, chemical

contributors to cell injury: infectious

viral

fungal

protozoan

bacterial

contributors to cell injury: physical

thermal: chemical, burn

mechanical: stubbing toe

contributors to cell injury: deficit

water

oxygen

nutrients

temperature

waste disposal

targets and mechanisms of cell injury

mitochondria: energy deficit/ATP depletion

membranes (cell and organelles)

cannot repair or build new things in cells (protein synthesis)

cytoskeleton proteolysis

genetic apparatus (DNA): damaged DNA = all cell is bad

altered ion concentration

inactivation of enzymes

increased ROS production

detachment of ribosomes

types of injury

reversible cellular injuries: most injuries, cellular accumulations (things that should be transporting are accumulating and cannot pull what we need), cellular adaptation

irreversible: necrosis, apoptosis, cellular aging

intracellular accumulations

excess accumulations of substances in cells

fluid: most common and simple

fat

proteins

materials cannot be processed or transported appropriately: endogenous enzymes, exogenous substances

lead to cellular injury: toxic, immune response, overcrowding/resource consumption

hydropic swelling

first thing we see: edema

first sign of reversible cellular injury

lack of sufficient ATP → Na-K pump failure → Na ions accumulate within cell→water follows Na→ intracellular edema

sodium cannot move out, water passively diffuse sodium into cells

edema

peripheral edema: on outer limbs like leg, arm, feet, hand, swelling in these areas

abnormal accumulation of fluid in organs, interstitial tissue

check w/palpation: how long does indentation take to recover

dependent edema

shows up because of gravity, gravity pulls fluid down when sitting (leg hanging)

intracellular accumulations

abnormal metabolism

defect in protein folding, transport

lack of enzyme

ingestion of indigestible materials (unable to degrade)

abnormal metabolsim

faulty metabolism of normal intracellular substances

Healthy: cells are in collective uniformity, look alike and cohesive

Fatty liver disease: not working together, empty spots, organ malfunction

megaly

abnormal enlargement by accumulation of a specific organ d/t edema or other intracellular accumulations

hepatomegaly

splenomegaly

hydropic swelling is a sign of cellular injury associated with

Na+ and K+ pump dysfunction

water follows Na accumulation

hydropic = water accumulate

reversible: cellular adaptations: atrophy

lack of use (muscle atrophy) so decreased cell size occurs, still functional

reversible: cellular adaptations: hypertrophy

resistance training

increased cell size

more energy to become bigger

hyperplasia

metabolic process (glands)

increased cell number

causes: increased functional demand, hormonal stimulation, persistent injury, chronic irritation

metaplasia

demand is changing

conversion of one cell type to another

changing specialization

cause: persistent injury

fully reversible when injurious stimulation is removed

ex: esophageal lining can protect from acid, lining becomes like stomach lining becomes scar tissue

goes back to healthy once acid doesn’t keep rising

chronic = displastic = cancer

dysplasia

dysfunctional, precursor to cancer

disorderly growth

adaptive effort gone astray

irregular sizes and shapes

atrophy

conservation effort: minimize energy use/demand and nutrient consumption

causes: disuse, denervation: no longer communicating with nerve, ineffective

ischemia: lack of blood supply (reversible to a point), adequate O2, cells can die

starvation: lack of appropriate nutrition

endocrine

injury

what is the response to increased metabolic demand in glandular tissue

hyperplasia

necrosis

premature cell death

caused by factors external to the cell

most commonly related to ischemia and oxygen deprivation

prolonged ischemia = necrosis

nucleus shrinks

organelles cease to function

plasma membrane dysfunction and rupture

adjacent cells become inflamed

apoptosis

programmed cell death

generally triggered by normal, healthy processes in body

most commonly related to normal aging process

nucleus divides

organelles redistribute

ATP production continues

plasma membrane remains intact while dividing into smaller apoptotic cells

adjacent cells unaffected (cleaner death)

necrosis vs apoptosis

necrosis:

regulation: ischemia trauma and ATP depletion

Control: uncontrolled

Cell shape: swelling

Plasma membrane integrity: collapse or rupture

cellular content: leakage to extracellular fluid

DNA: no fragmentation

energy: not required

inflammatory response: present

mediator: caspase-independent

necrosis vs apoptosis pt 2

apoptosis, ex: skin and hair cells:

regulation: genetic program

control: controlled

cell shape: shrinkage, condensed

plasma membrane integrity: maintained

cellular content: packaged in apoptotic bodies

DNA: fragmentation

energy: ATP

inflammatory resp: absent

mediator: caspase

ischemia

most common cause of cell injury

inadequate blood supply to tissue or organ (circulation)

disruption of oxygen supply + accumulation of metabolic waste: lactic acidosis (irritant, anaerobic), cellular proteins and enzymes become dysfunctional

ischemic injury is reversible up to point

cell death occurs when plasma, mitochondrial, lysosomal membranes damaged

ischemia reperfusion injury

a lot of waste dumped at once, reperfusion to other cells

calcium overload + formation of free radicals → subsequent inflammation

ischemia common causes

ischemia: pain

thrombosis: blood clot, more in veins (DVT, deep vein thrombosis), blood clot where we don’t need it, in legs, can travel to lung and cause pulmonary embolism

embolism: blood clot “embolize” travel to heart and brain

trauma

arterial insufficiency: aneurism, constriction, hypovolemia, anemia

ischemia general symptoms/signs include

fever

malaise

tachycardia

increased WBC's

loss of apetite

ischemic cascade

ischemia: nutrient deficiency, oxygen deficit, waste accumulation

damage to cellular structures: plasma membrane, nucleus, mitochondrion, endoplasmic reticulum and ribosomes, Golgi apparatus, lysosomes

necrosis: autolyzing proteolytic enzymes, membrane ruptures, cell dissolution

types of necrosis

coagulative (most common): solid tissues and organs

liquefactive: brain

fat: adipose tissue

caseous: lung

coagulative

injured cell becomes encapsulated by denatured proteins d/t lack of lysosomal enzymes

general tissue structure remains intact while slowly dissolving by proteolytic enzymes (takes weeks)

even when cell dies, still looks like a version of before, maintain original structure, ex: still looks like version of toes

liquefaction necrosis

digestive enzymes rapidly dissolve affected cells into liquid viscous mass

turn into liquid, mostly in brain

typically in tissue lacking strong connective structure

often localized infection that results in an abscess or cysts

fat necrosis

injury to fatty tissue

often associated with release of pancreatic enzymes d/t pancreatitis

seen in great trauma or surgical cases: around fatty tissues

caseous necrossi

origin of word: cheesy

unique type of cell deaths seen in lung tissue infected with/TB

incomplete proteolytic digestion of necrotic tissue

gangrene

cellular death in large area of tissue

results from interruption of blood supply to particular part of the body

three types: dry gangrene, wet gangrene, gas gangrene

dry gangrene

coagulative necrosis

characterized by blackened, dry, wrinkled tissue separated by a line of demarcation from healthy tissue

wait and see how much tissue can be saved or removed all at once

do not apply moisture or dressings

keep dry

monitor for drainage, odor, erythema at edges or increased pain

wet gangrene

form of liquefactive necrosis - does not look like toes anymore

typically found in internal organs

can be fatal

gas gangrene

results from infection of necrotic tissue by anaerobic bacteria (clostridium)

invade tissue, create gas air in soft tissue: subcutaneous emphizema

gas bubble in damaged muscle tissue

also have crepitus: crunchy, bone on bone friction = crepitus, palpitable

gas forming myonecrosis

very regional, only in the desert, black gasses over purple swollen leg

treatments for gangrene: removal of dead tissue

when appropriate

amputation

debridement: for a patch, mechanical, remove bandage/dead tissue

maggots: wound treatment, debridement

surgical: scalpel

chemical: enzyme, seaweed

treatment for gangrene pt 2

antimicrobial agents

revascularization: promote good circulation, surgical transposition: move blood vessel around, angioplasty, leeches: especially in plastic surgery, pull blood to mouth

hyperbaric oxygen therapy (for gas gangrene)

cellular aging

cumulative result of factors that cause cellular/molecular damage

progressive decline in proliferation and reparative capacity of cells

exposure to environmental factors

responsible mechanisms: DNA damage, reduced proliferative capacity of stem cells, accumulation of metabolic damage

physiologic changes: age related decrease in functional reserve, inability to adapt to environmental demand

apoptosis over time…

slows down, less elasticity, baldness

regulated or programmed cel death

because of extrinsic and intrinsic factors

not associated with systemic manifestation of inflammation

rate of apoptosis → cell replacement = impaired tissue/organ function

programmed senescence theory

intrinsic genetic program

decline in production of telomerase over time results in shortened telomeres with each cell division

cell dies when critical low is reached

somatic death

death of entire organism

no inflammation or immunologic response occurs prior to death

general features: cessation of respiration and heartbeat, temperature drops, pallor due to blood and body fluid collection in dependent areas

presence of stiffened muscles after death (rigor mortis)

release of lytic enzymes in body tissues: postmortem autolysis

determination of brain death as proof of somatic death

absence of brainstem reflexes, electrical brain waves, and cerebral blood flow