KNES 495 - mechanisms of disease

age-related diseases

• heart disease

• cancers

• strokes

• parkinson’s

• alzheimer’s

• diabetes

• kidney disease

aging and disease - prevalence

• age-related disease increase in prevalence with age

causes of disease

• heredity

• trauma

  • higher risk with aging

• inflammation and infection

  • more susceptible with aging

• nutritional imbalance

  • can be age-related

• impaired immunity

  • can be age-related

• controllable lifestyle choices

causes of disease - heredity

• congenital defects

causes of disease - heredity: congenital defects types

• single gene

• several genes

• chromosome abnormality

causes of disease - heredity: congenital defects, single gene example

ex. cystic fibrosis

causes of disease - heredity: congenital defects, several genes (polygenic) example

• gout, hypertension

  • can be age-related

causes of disease - heredity: congenital defects, chromosome abnormality examples

• klinefelter’s, down’s

causes of disease - trauma

• leading cause of death in children and young adults

  • falls

  • poisons

  • vehicle accidents

• seniors more prone to trauma

  • slower recovery

causes of disease - inflammation and infection

• inflammation

  • heat, swelling

• infection

  • “-itis” suffix

chronic inflammation leads to

many age-related diseases

edema

• accumulation of water in the interstitial space

  • local or within an organ system

  • can affect organ function

edema examples

• pulmonary edema

• swelling with injury

mechanisms that cause edema

• blood changes

  • increased blood pressure

  • decreased osmotic pressure

• increased capillary permeability

• lymphatic obstruction

causes of disease - nutritional imbalance

• malnutrition

• obesity

• vitamin or mineral deficiency

cachexia

• thin appearance

• related to malnutrition

causes of disease - impaired immunity

• allergy

• auto-immunity

• immunodeficiency

• aging

cellular adaptation

• external or internal stressors alter structure and function

  • cells, tissues, organs

examples of cellular adaptation

• pregnant uterus

• dilation of heart after an attack

types of cellular adapation

• atrophy

• hypertrophy

• hyperplasia

• dysplasia

• metaplasia

atrophy

• no growth

• decrease in cell size or shape

• from decreased workload

• ex. muscle atrophy with casting

hypertrophy

• excess growth

• increase in cell size

• due to overwork

• ex. cardiac hypertrophy

hyperplasia

• increase in cell number

• with increased workload

  • compensation or hormonal

• ex. thyroid goiter

dysplasia

• alteration of size, shape, or organization

  • ex. slow-growing tumours

metaplasia

• change of cell type, differentiate

• ex. acid-reflux effects on esophagus - columnar cells that secrete mucous

neoplasia of a cell

• excessive # of abnormal cells

  • ex. malignant cancer

hyperplasias and neoplasms - difference

• hyperplasia = excessive growth

  • ex. goiter

• neoplasm = new growth

  • ex. tumours

  • “-oma” suffix - carcinoma, melanoma, sarcoma

cellular injury

• hypoxic

• chemical

• infectious

• physical agents

• genetic factors

• immunologic/inflammatory

• nutritional imbalances

manifestation of cellular injury

• with injury,

  • metabolism changes

  • swelling

    • damaged membrane

    • changes in electrolytes

  • increased lipids

  • organelle changes

signs and symptoms of cellular change

• fatigue and malaise

• altered appetite

• fever

• increased HR

• pain

cell fates

• necrosis

• apoptosis

necrosis

• cell death results in tissue dysfunction and organ failure

apoptosis

• programmed cell death allows for repair or removal of unnecessary cells

• pathological (disease, stress, or DNA damage)

• physiological (ex. removal of cells embryonically or damaged cells in repair)

how does apoptosis happen

• injured cell releases enzymes that engulf and destroy cell

  • cells shrink

  • allows tissues to repair and possibly regenerate

apoptosis - pathway of cell death

regulated suicide

• organized fragmentation of DNA

• fragmentation of nucleus

• blebs (bulges in membrane) form

• apoptotic bodies (cell fragments are released

  • apoptotic bodies are phagocytized

• controlled by specific genes

necrosis - process

• morphologic expression of cell death

  • inflammation

• progressive disintegration of cell structure

  • initiated by overwhelming stress

  • usually elicits an acute inflammatory cell response (neutrophils may be present)

• pathological cell death

  • many cells swell and rupture

types of necrosis

• coagulative

  • ischemia

• liquefactive (pus)

• caseous

  • cheese-like

• fatty

gangrenous necrosis

• definition and types

• cell death over a wide area

• dry

  • limb ends

  • ischemia

• wet

  • wet tissues

  • bacterial

• gas

  • bacterial

  • produces gas

necrosis vs apoptosis - area

necrosis

• affects large areas

apoptosis

• affects scattered cells

necrosis vs apoptosis - intracellular environment

necrosis

• intracellular environment is lost early

apoptosis

• intracellular environment maintained in early stages

necrosis vs apoptosis - cells swell or contract?

necrosis

• cells and organelles swell

apoptosis

• cells contract, fragmentation

necrosis vs apoptosis - inflammation?

necrosis

• inflammation, neutrophils

apoptosis

• phagocytosis by macrophages or enzymes

necrosis vs apoptosis - DNA break up

necrosis

• DNA randomly breaks up

apoptosis

• DNA breaks up at specific points

shock

• inadequate perfusion to tissues

• will cause cellular death

• either heart or vessel or blood causes

types of shock

• cardiogenic

  • weak heart

• hypovolemic

  • bleeding, dehydration

• neurogenic

• anaphylactic

  • allergy

• septic

  • infections, toxins

multiple organ dysfunction syndrome (MODS)

• progressive impairment of two or more organ systems

  • uncontrolled inflammatory response

    • illness or injury

primary MODS

• organ damage with specific cause

  • ischemia, shock, trauma, surgery

• stress and inflammation may be mild

  • neutrophils, macrophages, mast cells are “primed” by cytokines

secondary MODS

• in subsequent injury, ischemia, or infection, “primed” cells are activated

  • exaggerated inflammatory response

  • self-perpetuating cycle

  • damage and vasodilation

  • further damage

MODS at 24 hours

• low-grade fever

• tachycardia

  • fast HR

• dyspnea

  • breathing difficulty

• altered mental status

• general hypermetabolic state

mods within 24-72 hours

• pulmonary failure begins

mods within 7-10 days

• heptaic failure begins

  • ascites

• intestinal failure begins

• renal failure begins

MODS within 14-21 days

• renal and hepatic failure intensify

• gastrointestinal collapse

• immune system collapse

MODS after 21 days

• hematological failure begins

• myocardial failure begins

• altered mental status

  • encephalopathy

• death

“integrative diseases”

• diseases which affect other organ systems and can cause secondary failure

  • heart failure

  • COPD

  • kidney failure

  • liver failure