EXAM 1 General Concepts of Pathophysiology Flashcards
what reflects changes causing health to fall outside the normal range (loss of homeostasis)?
Disease
To treat disease effectively, we must understand what 3 things?
- Normal processes being disturbed
- Characteristics of the disturbance
- Secondary effects of the disturbances
Example of Secondary effects of the disturbances
comorbidity
complications
Factors Affecting “Normal”
- Genetic variations (e.g., Gilbert’s syndrome)
- Cultural variations (e.g., diet, literacy)
- Age differences (e.g., body composition)
- Gender differences (e.g., Hct, Hgb)
- Situational differences (e.g., altitude-Hct)
- Diurnal variations (e.g., serum cortisol)
what is Etiology?
the cause(s) or reason(s) for disease or functional alteration(s)
what is pathogenesis?
the sequence of events in response to injury or disease
what characteristic changes in the appearance of tissues or cells associated with disease
Morphologic changes
Functional alterations and clinical significance are determined by ____.
cellular changes:
which result in signs, symptoms, clinical course and expected outcome
what is natural history?
Natural history is the progression from initial change to recovery or death
what is a lesion?
Lesion is a tissue abnormality caused by disease or trauma
what is a sign?
is an objective finding, documentable (you can experience it)
What is a symptom
is a subjective feeling or complaint (what the patient says has happened)
what are Sequelae
Sequelae are conditions resulting from disease or trauma
what are complications?
Complication is a new problem resulting from the presence of a disease
(sinusitis from pneumonia)
_____ describes the disappearance of a disease and return of health
resolution
Alterations/mutations result in abnormal protein production (e.g., cystic fibrosis) is what Etiologic Classification of Disease?
Inherited (familial)
Prenatal (in utero) and neonatal (1st two months) disorders of development (e.g., atrial-septal defect) is what Etiologic Classification of Disease?
Congenital
Inherited or acquired deficiencies or abnormalities of metabolic systems or processes (e.g., phenylketonuria, diabetes) is what Etiologic Classification of Disease?
Metabolic
disorders that appear in utero or appear shortly after birth?
Congenital disease
Gradual breakdown of tissue and loss of function (e.g., osteoarthritis) is what Etiologic Classification of Disease?
Degenerative
Loss of growth control (e.g., lung cancer) is what Etiologic Classification of Disease?
Neoplastic
Over- or under-responsive immune system, against self (e.g., rheumatoid arthritis) or environmental antigens (e.g., poison ivy rash) is what Etiologic Classification of Disease?
Immunologic
poison ivy is what type of disorder?
Immunologic disease
Microorganisms, parasites, toxins, tissue destruction (e.g., influenza) are what Etiologic Classification of Disease?
Infectious
Trauma or toxicity (e.g., burn) are what Etiologic Classification of Disease?
Physical agent-induced
Deficiency and excess of nutrients (e.g., vitamin D deficiency, hypervitaminosis A) are what Etiologic Classification of Disease?
Nutritional
Caused by the health care system (e.g., errors, therapy, complication, misdiagnosis) is what Etiologic Classification of Disease?
Iatrogenic
Originating in the mind (e.g., somatoform disorders) is what Etiologic Classification of Disease?
Psychogenic
when Cause is unknown (e.g., idiopathic scoliosis) what is the Etiologic Classification of Disease?
Idiopathic
misdiagnosis is an example of what classification of disease?
Iatrogenic
Cell-cell communication occurs via secreted molecules (____) which interact with complementary cell-associated molecules (____)
ligands
receptors
your pt presents with a complaint of fatigue and cough. while listening to heart you hear murmur. when asked pt says she has palpitations. what finding is a sign?
murmur
Hormone binding to receptor communicates signal through cell membrane via ion channels, enzyme activation (e.g., insulin receptor) – primarily water soluble hormones
this is example of what type of receptors?
Cell surface receptors
Hormone crosses membrane and binds to intracellular receptors which communicate the signal to the nucleus (e.g., cortisol receptor) – primarily lipid soluble hormones
this is example of what type of receptors?
Intracellular receptors
type of receptor on cell membrane and are associated with water soluble hormones
Cell surface receptors
type of receptor that is associated with lipid soluble molecules
Intracellular receptors
examples of lipid soluble molecules
cortisol. estrogen, testosterone
Four types of cell-cell communication
- autocrine
- synaptic
- paracrine
- endocrine
Cells respond to signaling molecules that they secrete, providing feedback to themselves (e.g., T lymphocytes and IL-2) is what type of cell-cell communication?
autocrine
Rapid onset, short duration, very specific effect is what type of cell-cell communication?
autocrine
Nervous system (e.g., neurotransmitters in synapse) is what type of cell-cell communication?
Synaptic
Rapid onset, short duration, very specific effect
is what type of cell-cell communication?
Synaptic
Chemicals secreted into local area, then rapidly destroyed so only local cells affected (e.g., histamine, eicosanoids)
is what type of cell-cell communication?
Paracrine
Slight delay in action, intermediate duration, several actions
is what type of cell-cell communication?
Paracrine
Mediators which travel via bloodstream, target cells widely distributed (e.g., protein and steroid hormones) is what type of cell-cell communication?
Endocrine
Delayed action, long duration, multiple significant actions is what type of cell-cell communication?
Endocrine
when hormone travels through bloodstream and is distributed everywhere is what type of cell communication?
Endocrine
Cell growth and division is strictly regulated to address needs of ________, ____, and ____..
tissue growth, development and maintenance
Somatic cell division where each daughter cell receives an identical and complete set of 46 chromosomes
Mitosis
Gamete (egg and sperm) cell division in which the number of chromosomes is reduced in half (diploid to haploid, 23 in humans)
Meiosis
Growth factors are hormones (autocrine, paracrine, endocrine) secreted by cells which affect _________.
the rate of division and path of differentiation of themselves or other cells
___ helps cells adapt to stress
Adaptation
____ occurs when cells are unable to adapt to stress
injury
2 types of cell injury
Reversible injury
Irreversible injury
___ is the end stage of irreversible cellular injury
death
2 types of cell death
necrosis and apoptosis
what changes start immediately upon injury?
biochemical
what changes occur after biochemical derangements?
morphologic
The response of the cell to injury depends on:
- Length of time of exposure to the injurious agent
- Dose of injurious agent
- Type of cell and its ability to adapt
_____ are less able to adapt to hypoxia than cardiac muscle cells
neurons
small dose causes what kind of changes?
minimal
Injurious agents interfere with membrane-bound calcium ATPase, allowing ______ to enter cytosol and accumulate in mitochondria and endoplasmic reticulum
calcium
Increased intracellular calcium activates (4 enzymes)
- Phospholipases
- Proteases
- ATPases
- Endonucleases
enzyme that destroys membrane phospholipids
Phospholipases
enzyme that destroys cell proteins, e.g., cytoskeleton
proteases
enzyme that results in ATP depletion
ATPases
enzyme that degrades nuclear DNA
Endonucleases
Increased intracellular calcium activates enzymes which result in?
Results in biochemical changes, water influx, organelle and cell swelling and loss of function
Decrease/loss of ATP within cell due to decrease in oxidative phosphorylation by mitochondria, leading to: (3 things)
- Failure of Na+/K+ co-transporters
- Increased anaerobic glycolysis, generating lactic acid
- Reduced intracellular pH, causing some morphologic changes of cell injury (e.g., denaturing proteins, affecting enzyme function)
does lactic acid denature proteins?
yes
does lactic acid affect acid base balance?
yes
___ changes causes morphological changes
biochemical
Morphologic features
of cell injury (5)
- Increase in cell size (swelling due to Na+/K+ co-transporter failure)
- Swelling of mitochondria and endoplasmic reticulum (water influx)
- Nuclear and chromosomal changes (decreased pH)
- Detachment of ribosomes from endoplasmic reticulum (ATP depletion)
- Small cytoplasmic blebs (cytoskeleton disruption)
morphological changes in cell injury reflect _____ damage.
membrane
while examining a ct scan you notice a calcium deposit in the pts coronary artery, this is an indicator of what?
necrotic cell death
Critical biochemical events
2
- Inability to reverse mitochondrial dysfunction
2. Profound disturbances in plasma membrane function
Progressive degradation of cell proteins and membrane phospholipids
Membrane ion pump disruption and water influx
Cytoskeletal abnormalities
Cell protein and lipid oxidation (oxygen radical injury)
these are all disturbances in ______.
plasma membrane function
All cells die either by _______.
necrosis or apoptosis
_____ is the type of cell death resulting from irreversible cell injury
Necrosis
this type of cell death indicates a pathologic process
necrosis
this type of cell death Involves injury to many cells within an area of tissue
necrosis
Necrotic cells/tissues initiate an ________, which may further injure surrounding cells and tissues
inflammatory response
in necrosis, Release of_____ dissolves affected tissue, may injure surrounding cells and tissues
lysosomal enzymes
type of necrosis that results from denaturation of proteins (e.g., ischemic death)
Coagulative necrosis
type of necrosis that results from autodigestion resulting in cells dissolving (e.g., bacterial tissue infections and abscess formation)
Liquefactive necrosis
type of necrosis that occurs with chronic and granulomatous inflammation, looks “cheesy” (e.g., tuberculosis)
Caseous necrosis
heart attack has what type of necrosis in cardiac muscle?
Coagulative necrosis
type of necrosis that occurs when fat cells become nectotic, both liquefactive and coagulative necrosis occur (e.g., acute pancreatis)
Fat necrosis
bacterial infections/ rapidly growing tumors/ abbesses are associated with what type of necrosis
Liquefactive necrosis
granulomas/ tuberculosis are associated with what type of necrosis?
Caseous necrosis
type of necrosis associated with adipose tissue
fat necrosis
IM injections (corticosteroid shots) have to be in muscle not subcutaneous because it can cause what type of necrosis?
fat necrosis
programmed cell death
Apoptosis
calcium deposits occurs in areas of _______.
necrotic cell death
______ is a distinctive pattern of cell death occurring in specific physiologic and pathologic circumstances
.
apoptosis
Physiologic examples of apoptosis (2)
- Programmed cell death that occurs during embryogenesis and development
- Hormonal dependent changes in adult tissues
Pathologic examples of apoptosis
Certain neurodegenerative diseases, gradual ischemic damage, autoimmune disorders, cancer
Morphologic characteristics of apoptosis (3)
- Involves single cells or small groups of cells
- Characteristic nucleus and chromatin changes
- Pronounced cytoplasmic blebbing with formation of membrane-bound apoptotic bodies
is apoptosis associated with inflammation?
NO
are lysosomal enzymes released in apoptosis?
NO
when T lymphocytes are killed in thymus gland, the thymus is not inflamed because it undergoes what kind of cell death?
apoptosis
large number of cells are involved with what type of cell death?
necrosis
single cells or small groups of cells are involved with what type of cell death?
apoptosis
dead cells by apoptosis are removed by ______.
macrophages
you identify an area of tissue death on right chest with an abscess and inflammation, what process is most likely responsible for the presentation?
necrosis
what is atrophy?
Shrinkage in cell size by loss of cell substance
If prolonged, atrophy may progress to cell death by _______.
apoptosis
This term also used to describe reduction in organ size, usually resulting from disease
atrophy
type of atrophy with Normal changes in cells and organs, generally related to developmental or hormonal changes
Physiologic atrophy
Embryo development,
Decreased workload,
Change in degree of endocrine stimulation, and
Aging (i.e., reduced skeletal muscle mass)
all result in what type of atrophy?
physiologic
type of atrophy with Changes in cells and organs related to some pathology
Pathologic atrophy
Loss of innervation (e.g., carpal tunnel syndrome) is what type of atrophy?
Pathologic atrophy
Diminished blood supply (e.g., vascular dementia) is what type of atrophy?
Pathologic atrophy
Inadequate nutrition (e.g., muscle wasting) is what type of atrophy?
Pathologic atrophy
Loss of endocrine stimulation (e.g., pituitary pathology) is what type of atrophy?
Pathologic atrophy
hypothenar eminence will be atrophied in what syndrome?
carpel tunnel syndrome
what is hypertrophy?
An increase in the size of cells with resulting increase in organ size
in hypertrophy, Size is related to _______.
increased cellular components ( e.g., myofilaments)
hypertrophy is Physiologic, or pathologic, or both
both
______ related to increased functional demand or specific hormonal stimulation
Physiologic hypertrophy
does Physiologic hypertrophy enhance function
yes
hypertrophy type Physiologically related to increased functional demand or specific hormonal stimulation, causing pathology
Pathologic hypertrophy
hypertrophy type that results in reduced function
Pathologic hypertrophy
Acromegaly is an example of ______ hypertrophy, caused by growth hormone excess
Pathologic hypertrophy
what is an increase in the number of cells in an organ or tissue, possibly resulting in increased volume
hyperplasia
Requires DNA synthesis, only occurs in cells capable of proliferating
hyperplasia
Stimulated by growth factors, some cytokines and hormones
hyperplasia
is hyperplasia physiologic, pathologic, or both
both
what is physiologic hyperplasia
- hormonal
i. e. menstrual cycle - compensatory
i. e. wound healing
what is pathologic hyperplasia
- may predispose to neoplasm due to increased DNA synthesis
i. e. proliferation of cells of prostate gland causing benign prostatic hyperplasia
A reversible change in which one adult cell type is replaced by another adult cell type in order to function under stress or other pathologic stimulus
metaplasia
What is usually caused by chronic irritation and inflammation and may predispose to neoplasia
metaplasia
example of metaplasia
Squamous to columnar epithelium change due to acid reflux in distal esophagus – Barrett’s metaplasia
Is metaplasia ever normal?
NO - implied that some sort of stress is occurring
Deranged cell growth within a tissue, with cells of varied shape, size, appearance, associated with genetic mutations
dysplasia
Loses the morphological characteristics of mature, differentiated cells
dysplasia
_______ cells may become _______ with continued exposure to offending agent
Metaplastic cells may become dysplastic with continued exposure to offending agent
- Related to chronic irritation, inflammation, other pathologic stimuli (e.g., human papilloma virus infection)
- Considered premalignant
dysplasia
stages of wound healing
- Inflammatory
- proliferative
- remodeling
- immediate to 2-5 days
- Hemostasis (vasoconstriction, platelet aggregation, thrombus formation)
- Inflammation (vasodilation, diapedesis and phagocytosis)
inflammatory phase
- 2 days to 3 weeks
- Granulation (plasma protein deposition, fibroblast ingrowth and collagen deposition, capillary ingrowth)
- Contraction (wound edges begin to pull together)
- Epithelialization (epithelial cells grow over new granulation tissue to 3 cm)
proliferative phase
- 3 weeks to 1-2 years
- Reorganization of fibrotic tissue (scar), vasculature
- Tissue tensile strength increases up to ~80% its original strength
remodeling phase
Wound edges are approximated (brought together) by sutures or other mechanisms to enhance healing rate and outcome
Healing by first intention (primary union)
Wound edges are not approximated, defect fills in over time
Healing by second intention (secondary union)
results in a large tissue defect that must be filled by gradual expansion of granulation tissue
healing by second intention
- Granulation tissue must grow in from margins
- More intense inflammation, much longer to heal
- Increased likelihood for significant scarring and wound contracture
healing by second intention
should you let wounds “air out”?
NO - don’t want them to dry out bc then will have to remake new capillaries and epithelial cells
Repair of damaged tissue requires replacement of parenchymal cells AND stromal proteins
fibrosis
- Fibroblast migration (on plasma protein matrix) and proliferation
- Collagen matrix deposition
- Growth of new blood vessels (angiogenesis)
- Remodeling
components of fibrosis
what is the first type of tissue to be produced?
granulation tissue
- New connective tissue from fibroblasts and capillary networks that form at the base of a wound
- Typically grows from the base of a wound and fills the wound slowly (may over-grow – “proud flesh”)
granulation tissue
Result of site-specific changes in balance of collagen / matrix synthesis versus degradation by tissue metalloproteinases
tissue remodeling
produced by many tissue cells, and they are rapidly inactivated by tissue inhibitors of metalloproteinase produced by many of the same tissues
metalloproteinases
what are some modifiers of wound healing?
Nutrition Metabolic status Circulatory status Glucocorticoids Infection Foreign bodies i Size, location, type of wound Early stress on wound
Tensile strength of wound increases slowly to ___% by __-__ months (its new maximum strength)
Tensile strength of wound increases slowly to 80% by 3-12 months (its new maximum strength)
Increased ____ strength related to net collagen ____ and collagen _____ _______
Increased tensile strength related to net collagen deposition and collagen cross linking
wound repair pathology
Dehiscence
Hypertrophic Scarring
Contracture
opening of a previously closed wound and associated with poor wound closure
dehiscence
- Causes include excessive stress, poor suture technique
Ie abdomen bc of viscera trying to push out against opening - Usually occurs between 7 and 10 days post operatively
dehiscence
- Should be assumed that the defect involves the entire wound (full length, full depth)
- May also be associated with ulceration in areas of impaired vascularity (e.g., sutures too tight)
dehiscence
- Genetic predisposition, especially with darker skin
- Excessive granulation tissue, blocks re-epithelialization
- Often hyperpigmented
hypertrophic scarring (keloid)
- Increased collagen and matrix deposition occurs as wound edges approach each other, followed by collagen crosslinking and “contraction”
- great with healing by second intention
wound contracture