Patho Inflammation/Tissue repair

cellular death

necrosis, hypoxia, ischemia, free radicals, chemicals, physical forces

inflammation

cellular, local, and systemic effects

acute and chronic

cell injury/death

cells adapt or die/mutate

cell injury leads to different cell response

types of cell injury

O2 deficiency

Physical agents

Infection

Nutrition

Workload imbalance

Aging

Chemicals

O2 deficiency cell injury

inadequate oxygenation of blood

physical agents cell injury

mechanical trauma (hit/puncture), extreme tempts, radiation (external or medical), electric shock

infection cell injury

different types of infectious microbes can replicate once they gain access to cells or tissues

nutrition cell injury

deficiencies, excesses, imbalances (overeating, undereating, poor diet, etc.)

workload imbalance cell injury

hypertrophy, hyperplasia, atrophy

aging cell injury

accumulated damage in cells to their proteins, lipids, nucleic acids

chemical cell injury

drugs, toxins: direct contact with tissues, can be ingested (toxic to cellular components)

ex: mitochondria/plasma membrane

hypoxia

- decreased ability to obtain or use O2

- most common cause of cell injury

- is problem is lack of O2 (suffocation) or lack of blood (anemia/hemorrhage)?

hypoxemia

reduced transfer for O2 from lung to blood

ischemia

decrease blood flow to tissues/organs

hypoxia causes

- may be lack of air, not enough hemoglobin to carry O2/lack of ability to carry, not enough flow to blood vessels, hypothermia, vasoconstriction of blood vessels

free radicals

- electrical charged atom missing an electron

- will attack a healthy atom to gain electron

- normal to produce some, including ROS, but better to reduce creation

Reactive oxygen species

free radicals created with metabolism of oxygen

antioxidants

healthy atoms that will share an electron with the free radical atom preventing it from attacking another healthy atom preventing cell damage

types of antioxidants

endogenous: produced by body, more potent

exogenous: can be injected, bananas/blueberries, etc.

endogenous antioxidant systems

come from within body, production of endogenous antioxidants decreases with age, contributes to premature aging and degenerative diseases

oxidative stress

over production of free radicals

plays major part in development of chronic/degenerative ailments

ex: cancer, arthritis, aging, autoimmune, cardio/neurdegen. diseases

free radicals and oxidants

play dual role as toxic and beneficial compounds (find balance)

can kill pathogens (part of immune response, regulate cell growth)

production of free radicals

produced either from normal cell metabolism (ex: inflammatory process) or situations or from external sources (pollution, smoke, radiation, medication)

counteract oxidative stress

producing antioxidants - either naturally (endogenous) or by consuming certain foods and supplements (exogenous)

sources of antioxidants

- vitamin C

- fruit/veg

- avoid processed food

- avoid high glycemic index, refined sugar/carbs

- limit processed/cured meats

- limit red meat

- dont reuse cooking oil

- limit alcohol

vit C (ascorbic acid)

most powerful water-soluble antioxidants found in blood plasma

asphyxiation

failure of cells to recieve/use O2

(suffocation, hanging, ligature, manual, drowning, carbon monoxide, chemical)

suffocation

systemic hypoxia, no air exchange in lungs, no O2 available

ex: bag over head, trapped in fridge, obstructed airway

hanging

V inverted on neck

ligature

horizontal mark, petechiae more common, internal injury rare

manual

severe internal damage, bruising/fractures of hyoid

drowning

no O2 exchange in lungs due to being fluid filled, prevent O2 delivery to tissues

carbon monoxide

binds to hemoglobin, unable to transport O2 in blood, causing headache, nausea, weakness, tinnitus, vomiting

carbon monoxide treatment

fresh air, hyperbaric chamber (high pressure O2 - force carbon monoxide off hemoglobin)

cyanide

blocks intercellular use of O2 - weakness, nausea, confusion, difficulty breathing, seizure, cardiac arrest

cyanide treatment

identify source, activated charcoal (orally if ingested), oxygen

trauma

effect on tissue metabolism, structure, function

ex: blunt/sharp force, GSWs

contusion

bruise

on skin or internal organs

ex: crush injury to muscle

laceration

ragged, irregular, split (quickly), torn, stretched (repeatedly)

abrasion

superficial laceration (scrape)

avulsion

only skin, loose or torn

fracture

multiple types

incised wound

longer than it is deep, straight or jagged, not always surgical

stab wound

deeper than it is long, can be surgical (more violent/bigger than puncture)

puncture wound

weapon has a sharp point but not sharp edges, small, quick

cell regeneration

type of recovery, not always positive mutation

ex: smokers expose trachea to continuous smoke, cells mutate to smoother cells, can lead to mutation causing cancer/scar tissue

cell death

regeneration not possible

apoptosis or necrosis

autophagy

like apoptosis (controlled)

cell recycles/kills parts of itself

tries to save itself by killing non-functional parts

purpose of autophagy

consumes own contents for nutrients as metabolic processes occurring in starvation and certain diseases (can prevent apoptosis, autophagy of certain cell contents)

apoptosis

- death of cells, normal and controlled part of organisms growth/development (orderly process)

- shrinks itself first (autophagy part)

cell life spans

cells have different lifespans

neutrophils (WBCs): 2 days

Middle of eye lense cells: lifetime

necrosis

swelling/bursting of cell membrane - can also mean death of most/all of cells in an organ or tissue due to disease or injury/failure of blood supply

(non-controlled, messy)

why is apoptosis controlled

has controlled cellular fragmentation, phagocytosis occurs as phagocyte envelops the cell and fragments

coagulative necrosis

- loss of nucleus with cellular outline preserved

- cellular degeneration is delayed - architecture is maintained (damaged but stays intact)

(kidney, heart, adrenal gland, dense organs)

what causes coagulative necrosis

ischemia (inadequate blood supply to organ) or infarction (obstruction of blood supply to an organ or region of tissue)

liquefactive necrosis

- neurons/brain (high content of lipid and water)

- transforms tissue into liquid caused by infarction or abcess

caseous necrosis

- lungs, caused by tuberculosis

- dead tissue appears as a soft and white proteinaceous dead cell mass (cottage cheese in xray) combo of liquefactive/coagulative

fatty necrosis

- breast cancer/other abdominal organs/pancreas

- cellular death in area of fatty tissue, usually harmless, can be surgically removed if bothersome, can go away on its own

gangrenous necrosis

severe hypoxic injury- interrupted blood supply, medium for bacterial growth and impedes healthy wound healing

- dry, wet, or gas

dry gangrene

coagulative necrosis (blood supply slowly reduced, ex: old ppl)

wet gangrene

liquefactive necrosis (blood supply suddenly reduced) pus released, very painful (ex: tourniquet, frostbite)

gas gangrene

infected of injured tissue by clostridium difficile bacteria - blood supply reduced, clostridium enters wound, gas produced

innate immunity

what we are born with (physical, chemical, cellular defenses against pathogens)

innate physical barriers

skin, chemicals in blood/body fluids (gastric enzymes), cilia in lung, mucus, acidic urine, immune system cells that attack foreign cells

how is innate immunity weakened

smoking abrasions on skin, using q tips in ears

inflammatory response

- rapid leakage of K+ leads to visible inflammation

- first responders: inflammatory cells and cytokines. Begin inflammatory response to trap bacteria and other offending agents or start healing injured tissue

- nonspecific attack caused by any assault to the body

inflammatory process

1. macrophages are activated - capillaries dilate/become permeable

2. fluid clotting agents move into tissues, clotting begings

3. chemokines released phagocytic cells attracted to site

4. healing begins

inflammation steps

- bacteria/virus enters

- damaged mast cells - histamine

- increase artial BF, decrease venous BF

- capillaries dilate/leak

- platelets/clotting factors migrate

- chemokines released

- phagocytic neutrophils come

- WBCs engulf pathogens, make pus

blood drawn for infection

determines level of WBC count (neutrophils most common), gauge level of infection

premature neutrophils

"bands"

presence in blood indicated acute infection

what is working at the site of inflammation

- 1st response is to stop bleeding, need platelets at site

- BVs dilate increasing permeability, allowing leakage at site

- platelets, cytokines (messengers), prostaglandins (mediate pathogenic mechs.)

- bradykinin and serotonin (further vascular permeability/vasodilation)

vascular side

activated macrophages cause vasodilation

BV diameter widens = further widening of BVs

burns

massive fluid shift that comes when there has been so much damage that the inflammatory process causes massive volumes of fluid to the interstitial spaces

signs of acute local inflammation

hallmark signs:

- pain

- heat, redness, swelling

- loss of function

pain

trauma at site potentially, but increased fluid at site triggers nerves and causes pain

heat, redness, swelling

due to increased permeability of capillaries - increased leakage from dilated capillaries - warm fluid that circulates at core now leaking into injured tissue

loss of function

from increased swelling and pain

inflammatory response goal

- stop/prevent bleeding - platelets

- limit infection - WBCs attack pathogens

- adaptive immune response or acquired immune system

adaptive/acquired immunity

more specific to pathogens - has memory - can develop due to an antigen (part of pathogen) or a vaccination

2nd line of defense before immune response

inflammatory response

infection

results if initial inflammatory response of sending neutrophils is not able to control the foreign pathogen

systemic signs of acute inflammation

release of cytokines causes:

- Fever

- WBC count

- process of recover

- lethargy

- ESR

- C-reactive protein

fever

local activity

with infection there is reset of body's thermostat, try to kill pathogen

caused by activity of cytokines or through local prostaglandins

WBC count

increased neutrophils (body trying to produce more neutrophils to fight infection)

if we see bands/shift = indicates acute infection

process of recovery

wont see premature neutrophils in blood stream

lethargy

stress induced - cytokines increase energy within cells - taxing on body

inflammatory agents can also affect BBB

inflammatory agents affecting BBB

cytokines may enter brain and cause neuro inflammatory response

lethargy

ESR

rate RBCs settle in saline solution

protein plasma increased in inflammation -RBCs stack/become heavier = settle faster

ESR uses

non specific but can be used to measure effect of therapy, if pt has elevated ESR, consider inflammation

C-reactive protein

made in liver

increases in response to inflammation

acute inflammation

- less than 2 weeks

- can become chronic if inflammatory response isnt successful

- visible, quick to diagnose

- redness, increased BF, edema, cardinal signs

chronic inflammation

- longer than 2 weeks

- hospital setting, not always visible

- response to prolonged irritation

chronic inflammation response

fibrosis (permanent scar tissue) and angiogenesis (form of new BVs)

no cardinal signs

how does chronic inflammation happen

- bacteria/foreign material in wound

- microorgs cell walls insensitive to phagocytes

- microorgs remian within macrophages

- chemicals can prolong repsonse

- autoimmune disorder

how does bacteria/foreign material cause chronic inflammation

can remain in wound and cause formation of pus or purulent drainage with incomplete wound healing

microorganisms with cell walls insensitive to breakdown of phagocytes

can cause chronic inflammation

ex: tuberculosis

microorganisms remaining within macrophages

can cause chronic inflammation

ex: some pneumonias, chlamydia, typhoid fever

chemicals prolonging inflammatory response

can cause chronic inflammation

ex: inhalants, dust, chemicals

autoimmune disorder

immune system mistakenly attacks own body tissues

can cause chronic inflammation

granuloma formation

- dense infiltration of lymphocytes and macrophages

- macrophages are unable to protect body/eliminate

- wall off infected area