Pathophysiology M1

Pathophysiology Definition

• pathos: suffering/disease

• ology: study of

  study of functional change in cells/tissue/organs altered by disease/injury

Signs v. Symptoms

sign: visibly observed, doctor

symptom: patient reports, not directly observed

Disease

• acute/chronic illness acquired/congenital

• causes physiologic dysfunction in body systems

• specific signs/symptoms

Etiology

know cause for disease

5 Ways Cells are altered

1. adaptation (r)

2. injury (r/nr)

3. death (necrosis/apoptosis)

4. aging

5. neoplasia

Cell Adaptation

• change in size, #, type

• helps with survival when under stress

• normal/adverse conditions

Cell Adaption: Atrophy

• ↓ cell size

• needs ↓ fuel/oxygen/energy

• result of disuse

• ex.brain (irreg)

Cell Adaption: Hypertrophy

• ↑ cell size

• ex. skeletal/heart muscle (adapt to ↑ workload)

Cell Adaption: Hyperplasia

• ↑ # of cells

• in tissues w cells that do mitosis

• in response to ↑ requirements on tissue

• ex. wound healing

Cell Adaption: Metaplasia

• reversible change of cell type

• reprograms undifferentiated stem cells

• ex. smokers (cell type replaced w more resilient cells to withstand ongoing damage)

Cell Adaption: Dysplasia

• abnormal changes in size/shape/organization of mature cells

• precursor of cancer

• ex. cancerous cells in cervix

Cell Adaption: Intracellular Accumulation

• buildup of material cell cant metabolize (busy/doesnt know what to do w)

• happens w old age

  endogenous: lipofuscin

  exogenous: tattoo pigment

lipofuscin

• yellow pigment in liver/heart from accumulation of undigested material

• produced during cell structure turnover

Cell Adaption: Calcification

• buildup of ca in tissues

  occurs in:

• damaged tissue → excess ca from damaged/dead cells in circulation

• normal tissue → hyperparathyroidism (in lungs/kidney)

Cell injury

• cell cant maintain homeostasis/adapt

• most diseases begin w injury (r/nr)

• caused by anything that disrupts the structure/deprives cell of oxygen/nutrients

4 major causes of cell injury

peanut butter chocolate nachos

P: physical agents (mech, elec, radiation)

B: biological (virus, bacteria, parisites)

C: chemical (drugs, alcohol)
N: Nutritional (deficiencies: macro/micronutrients. excess: fats/carbs)

Mechanism of cell injury: Hypoxia

H: not enough oxygen for cells (most common cause of cell injury)

causes:

• ischemia (reduced blood supply to tissue)

• hypoxemia (not enough oxygen in blood)

• thromboembolus (blood clot from elsewhere)

Pathophysiological Effects of Hypoxia

↓ ATP

• anaerobic resp → lactic acid buildup → ↓ pH

• ↓ activity of na-k pump (↑ intracellular Na → water enters cell → edema)

Mechanism of cell injury: Impaired calcium homeostasis

high intracellular ca =

• activates inappropriate enzymes → cell damage (membrane/nucleus)

• ↑ mitochondrial permeability → ↓ ATP production

Mechanism of cell injury: Free Radicals

• unstable molecules, contains unpaired outer electrons

• attack atoms of other molecules

• = cell damage/disease

  exogenous ex. exposure to air pollution

  endogenous ex. drug breakdown

• body protected by ROS scavengers

Apoptosis

• programmed cell death

• needs ATP

• only affects selected cells

• no inflammation

• ex. cell death by cytotoxic t cells

Apoptosis steps

1. cell structures shrink

2. nucleus destroyed by regulated enzymes → DNA fragments

3. membrane protrudes (blebs), enclosed fragments pinch off as apoptic bodies

Necrosis

• unregulated

• no ATP needed

• cell swells + bursts

• damages nearby tissues

• inflammation

  4 types: coagulative, liquefactive, caseous, fat

Coagulative Necrosis

• result of hypoxia

• characteristic of infarcts

• protein denaturation

• tissue → firm/opaque

• mainly in kidneys

Liquefactive Necrosis

• in bacterial/fungal infections

• tissues soften/liquefy (cells digested)

• pus filled pocket forms

• occurs in brain due to ischemia

Caseous Necrosis

• crumbly yellow

• combo of coagulative + liquefactive

• enclosed within inflammatory border

• often in lungs (tuberculosis)

Fat Necrosis

• areas of fat destruction

• results from leakage of pancreatic lipases into peritoneal cavity

• p fat digested into glycerol + fatty acids → liquifies

• fatty acids + ions in tissue = soap (white/opaque)

Gangrenenous Necrosis

• from severe hypoxic injury

• significant tissue area whose cells undergone necrosis

• types: dry, wet, gas

Dry Gangrene

• result of coagulative

• skin turns dry/dark

• interference w arterial blood supply

Wet Gangrene

• liquefactive

• internal organs

• area turns cold/swollen/black

• foul odour (bacterial infection)

• spreads easy

Gas Gangrene

• result of bacterial infection

• bacteria produces enzymes → destroys CT + causes bubbles of gas to form

Aging Theories- Programed (molecular)

changes that occur with ageing are programmed genetically

Aging Theories- Damage (senescence)

changes from accumulation DNA damage from random events (effects of free radical damage)

Acute v. Chronic

A: relatively severe, short term

C: continuous long term

Degenerative v. Communicable Disease

D: structure/function worsens over time

C: can be transferred b/w individuals

Iatrogenic v. Idiopathic

Iatrogenic: disease occurs as result of medical treatment

Idiopathic: disease w no identifiable cause

Congenital

Exacerbation

Remisson

C: disease present @ birth
E: severity of disease made worse
R: period where there's reduced severity of disease

Local v. Systemic

L: contained within one area

S: affects whole body

Pathogenesis

Prognosis

Syndrome

Risk Factor

Pa: how disease develops/originates

Pr: expected outcome of disease

S:combo of signs/symptoms that are characteristic of disease

RF: any characteristic that increases probability of developing disease

Infarcts

area of dead tissue (necrosis) caused by prolonged lack of blood flow

Mast Cell

• most important cellular activator of inflammation response

• in tissue (ex. skin/gut)

• release of granules containing histamine/active agents

Neutrophil

• most abundant in blood

• first on scene

• phagocytosis + activation of bactericidal mechanisms

• have pattern recognition receptors (bind PAMP’s no microbes for phagocytosis)

Macrophage

• phagocytosis + activation of bactericidal mechanisms

• antigen presentation

• initiates/controls later inflammation process

Endothelial Cells

• forms a metabolically active interface b/w blood + underlying tissue

• when active: allows leukocytes to move to site of damage

Platelets

• hemostasis

• activated by exposed collagen + clotting factors

• produce inflammatory mediators

Basophils

• release of histamine + vasoactive cytokines

• blood borne equivalent of mast cells

Eosinophil

• killing of antibody coated parasites

• important for hypersensitivity response

• increased during allergic reactions

2 groups of chemicals controlling inflammation

1. produced by liver (always present in plasma)

2. produced by cells (tissue/blood cells)

(short lived after activation)

Chem component: 3 protein systems from liver

Cake Kills Cute Actor

• clotting proteins / Kinin system

• Complement system

• acute phase proteins

Clotting Proteins / Kinin system

C: cascade of reactions → activate proteins (forms fibrin net) + form clot

K: cascade of reactions activate proteins, helps w inflammatory response

Complement System

cascade of reactions, activate proteins that:

1. kill pathogens

2. intensify reactions of inflammatory response

Acute Phase Proteins

• plasma concentrations are ↓/↑ in response to inflammation

• promotes fever, inflammation, leukocyte recruitment/activation

3 actions of Complement Pathway

1. degranulation of mast cells

2. opsonization

3. cytolysis

4 Chemicals Produced by cells

1. Histamine

2. Prostaglandins + Leukotrienes

3. Cytokines

4. Chemokines

HOT PIGS LIKE CHERRY COLA

Chemicals produced by cells: Histamine

• one of 1st chems released during acute inflammation

• ↑ vascular dilation/permeability

Chemicals produced by cells: Prostaglandins + Leukotrienes

• found in cell membranes + made from long fatty acid chains

• similar to histamine: indue inflammation, vasoconstriction, dilation

• L: cause of asthma + anaphylaxis

Chemicals produced by cells: Cytokines

• proteins made by cells (mainly macrophages)

• communicate w each other to produce affective inflammatory response

• ex effect: increasing WBC activity

Chemicals produced by cells: Chemokines

• type of cytokine

• act as chemoattractants, recruits/directs migration of immune/inflam cells

Inflammation

• initiated by all causes of cell injury

• innate immunity

• purpose: destroy infection, promote healing, limit spread

Acute Inflammation? 2 stages?

• effects: heat, swelling, pain, redness, loss of function

• usually local response

  stages

  1. vascular phase (immediate)

  2. cellular phase (influx of inflammatory cells)

Cells + Chemicals involved in Inflammatory Response

cells:

• mast cells, phagocytes, endothelial cells

chemicals:

• mast (histamine), injured tissue cells (cytokines/prostaglandins)

Acute Inflammation: Vascular Stage

1. damaged tissue cells release cytokines/chemokines/prostaglandins → IF

2. mast cells = activated by cytokines/other antigens

3. mast cells release histamine (vasodilation of blood vessels (SM relaxes) + ↑ permeability of capillaries)

4. fluid/blood proteins leak into IF of tissue → edema

5. vasodilation + edema = red, heat, swelling

Exudate

• produced by acute inflammation

• fluid that moves from vessels into tissues (w neutrophils + debris from phagocytosis)

• function: transportation (leukocytes/antibodies + nutrients), dilution of toxins

Serious Exudate

• low protein

• like fluid under blister (mild inflammation)

Fibrinous Exudate

• greater injury

• ↑ inflammation + vessels become more permeable

• release more proteins into tissue (fibrin)

• thick + sticky

Purulent Exudate

• “pus”

• serve inflammation w infection (neutrophil, protein, debris)

• large pocket (abscesses)

Hemorrhagic Exudate

• contains lots of RBC

• w severe inflammation

Chronic Inflammation

• greater than 2 weeks

• further injury to tissue + attempts to repair at same time

  3 causes:

• low grade, persistent infection (ex. virus)

• irritants body cant dispose of

• autoimmune disease

characteristics of chronic inflammation

1. dense infiltration of lymphocytes/macrophages/fibroblasts

2. little/no exudate

3. more tissue damage

   CI: causes tissue damages in diseases, persistent inflammation may be involved in cancer development

Granulomatous Chronic Infection

• subtype of chronic infection

• when particles not easily removed by immune system

• macrophages alter shape \eventually mass of cells is surrounded by CT (granuloma)

Systemic Inflammation

• inflammatory chems enter bloodstream = systemic

  1. acute phase response: release cytokines (cause fever/fatigue), increased production of acute phase proteins + immature neutrophils (shift to left)

  2. Leukocytes: increase in neutrophils (bacterial), eosinophils (parasitic), lymphocytes (viral)

Harmful effects of Inflammation

• phagocytes die → release lysosomal enzymes (can harm nearby tissue cells → w inflammation)

• tissue edema → blood flow to area decreases + less fluid leaves vessels (nutrient supply/waste removal may decrease)

Regeneration v. Replacement

Reg: injured tissues returned to almost original structure/function, ex. sunburn

Rep: replaces destroyed tissue w scar tissue (if large damage), scar tissue doesn’t carry out physiological function of destroyed tissue (provides strength)

Are they cable of regeneration? Labile? Stable? Fixed?

L: continually divides, ex. epithelial tissue

S: normally stops dividing when growth ceases (can regenerate if stimulated), ex. kidney

F (perm): cannot regenerate, replaced w scar tissue, ex. nerve cells

Phase I of Healing: Inflammation

• during acute inflammation, lasts 1/2 days

• platelets produce blood clot, fibrin net catches cells for healing process, release growth factors

• macrophages release growth factors, stimulate epithelial cell growth

Phase II of healing: Proliferation & new tissue formation

• 3-4 days after, up to 3 weeks

  1. blood clot broken down by enzymes

  2. macrophages clean up old clot + release cytokines attracting fibroblasts

  3. fibroblasts secrete collagen/gf

  4. granulation tissue (pink) grows in from healthy CT at edge of would

  5. myofibroblasts → wound contraction

  6. epithelial tissue grows over granulation tissue

Phase III of healing: remodelling & maturation

• epithelial cells in skin differentiate → forms layers of epidermis

• scar tissue is remodelled + collagen broken down + rebuilt (stronger)

• 3 weeks after injury

Clean Incisions vs. Open Wound

CI: ex. paper cut, not much sealing needed, healing of this type called primary intention

OW: scrape, needs lots of sealing, healing needed called secondary intention

Complication of healing: Fistula

• abnormal passageway b/w 2 structures (doesnt normally exist)

• develops through surgery/disease

Complication of Healing: Strictures

• narrowing of pathway

• can arise through inflammatory processes + scar tissue