Pathophysiology Exam 1

What is physiology

study of body function

What is pathophysiology

study of body’s response to dysfunction/disease (structural and functional change in cells/tissues/organs that cause or are caused by diseased)

example of physiology vs pathophysiology vs clinical manifestation

physiology: kidneys filter blood, make urine

pathophysiology: kidney failure - kidneys can’t filter blood or excrete waste

clinical manifestation: toxins in blood = fatigue, nausea, swelling

what is disease

interruption/cessation/disorder of body system/organ structure

• acute or chronic

• born with or acquired

• causes physiologic dysfunction

disease process (3 things)

etiology, predisposing factors, diagnosis

etiology

causative factors in a particular disease (specific cause)

• ex: biologic agent (influenza A bacteria causes flu)

predisposing factors

risk factors; things that promote disease development (not 100% cause)

• ex: sun exposure (risk factor for skin cancer)

4 types of predisposing/etiologic factors + examples

• biologic agents (bacteria/virus)

• physical force (trauma/burn/radiation)

• chemical agent (poison/alcohol)

• nutrition (excess/deficit)

what is diagnosis + process of it

identifying nature/cause of a health problem (identifying specific disease)

Process:

• medical history + interview (subjective)

• physical exam (objective)

• lab testing (primary tool for diagnosis)

Lab test interpretation (3 things)

reliability → if we repeat, same results?

validity → are we measuring what we mean to measure?

sensitivity/specificity → how correct is the test in identifying patient with disease/without disease?

gross level

can be seen with naked eye (organs/body systems)

microscopic level (2 types)

need microscope

• cellular (cytologic, cytogenetic tests)

• biopsy (excise small amounts of living tissue)

autopsy

exam after death

what is pathogenesis

development of disease (structural and functional changes in cells/tissues/organs)

what is clinical course

clinical evolution of the disease

acute illnes

severe, self-limiting, rapid development, short-term

ex: common cold

chronic illness (+ exacerbations/remission)

gradual, persists, might have periods

• exacerbation: aggravation

• remission: symptoms subside/absent

ex: HIV, diabetes

subacute illness

between acute and chronic, symptoms less intense but persist

subclinical state

no symptoms/signs present, but there are pathologic changes

latent stage

no symptoms/clinical signs

ex: pregnant women can carry infections that are only dangerous for newborns and not themselves

incubation period (+ CC/P)

stage from exposure time to onset (exposure to when you feel it)

CC: latent (no signs)

P: entered, colonizing site

prodromal period (+ CC/P)

early development of infectious disease (something feels off, don’t know what)

CC: signs non-specific/absent

P: multiplied, body reacting, not enough for specific symptoms

acute stage (+ CC/P)

specific signs of disease

CC: symptoms rapidly intensifying

P: rapidly multiplying, toxins in blood

convalescence (+ CC/P)

recovery period

CC: symptoms decreasing

P: immune system clearing tissue

clinical manifestations

characteristic signs/symptoms

signs

observed by provider (physical exam)

ex: swollen tonsils

symptoms

felt by patient (what they tell you)

ex: sore throat

syndrome

collection of signs/symptoms for specific illness

complications

adverse extensions of disease/outcomes of treatment (bad extras)

ex: cold can spread and become middle ear infection

precipitating factor

condition that triggers an acute episode/complication (something that happens that immediately causes a complication to happen - ex: new infection)

morphologic changes

structural change of tissue/cells bc of disease

therapy

measure to promote recovery/slow progression

rehabilitation

work with what ya got (make the most of damaged/diseased tissue)

ex: after stroke, train neurons to take over function of damaged neurons)

prognosis

probability of recovery

epidemiology

study of distribution, patterns, courses, risk factors of disease in populations (find cause and control/prevent)

disease case

existing case or # of new episodes of an illness

epidemic

spread of infectious disease within population or geographic area

pandemic

spread of infectious disease across continents

morbidity

number of people with disease

mortality

number of deaths (due to specific disease)

incidence

number of new cases within specific time period

prevalence

number of new cases + existing cases in specific time period (%)

how does natural history of disease help

• predictor of outcome of disease with no effective treatment

• information about history + potential of effective treatments give direction for preventive measures

primary disease prevention

remove risk factors, NO DISEASE

ex: vaccine

secondary disease prevention

have disease, but detect while curable

ex: pap smear, find cervical cancer in early, treatable stages

tertiary disease prevention

prevent further damage and reduce complications

ex: antibiotics

cellular adaptation def

cell response to escape and protect from injury

atrophy (physiologic + pathologic)

cell size decreases → leads to organ/tissue size decreasing

physiologic (normal/expected)

• occurs bc of less activity, less hormone stimulation, and aging

• ex: thymus involution (shrinks after puberty), muscle mass decrease while aging

pathologic (with disease/abnormal)

• occurs bc of low workload, pressure, low blood, bad nutrition, low hormones, nervous stimulation

• adaptation

  • dec protein synthesis

  • inc protein breakdown

  • autophagy

• ex: long time bed rest - disuse atrophy

hypertrophy

inc cell size → leads to organ/tissue size, bc of inc work/demand, hormones

physiologic

• normal

• ex: muscle growth while weight training

pathologic

• bc of disease/abnormal

• ex: left ventricular hypertrophy bc of hypertension

hyperplasia

increase in cell number (inc rate of cell division)

physiologic

• compensatory → organs can regenerate (after partial removal)

• hormonal → replace lost tissue/support new growth (ex: breast gland enlargement during pregnancy bc of estrogen

pathologic

• bc of excessive hormonal stimulation/effects of growth factor on target tissue

• ex: prostate enlargement

dysplasia

deranged cell growth, atypical hyperplasia

always pathologic

• abnormal change in size, shape, organization of mature cells

• not cancer (just potential for it)

• usually epithelial

• ex: cervical dysplasia (abnormal cells on cervix - HPV predisposing factor)

metaplasia

reversible replacement of one mature cell by another less mature cell type

response to chronic inflammation, irritation, smoking, acid reflux

• ex: barrett esophagus → chronic acid reflux makes squamous stomach lining into intestinal type cells

metaplasia vs dysplasia

meta: normal mature cells into another mature type

dysplasia: cells become abnormal in size, shape, organization

cellular inquiry

damage when cells are exposed to stress/harmful objects beyond ability to adapt

2 types of cellular inquiry

reversible → cells recover if stressed is removed

irreversible → cells die

common causes of cellular inquiry

• hypoxia (low O2)

• free radicals

• toxic chemicals

• immunologic reactions

• genetic factors

• nutritional imbalance

• trauma

how does cellular inquiry lead to cell death?

• decrease in ATP

• failure of Na/K pump

• cell swelling

• detachment of ribosomes

• decreased protein synthesis

• mitochondrial swelling

• leakage of digestive enzymes

• lysis of plasma membranes

ischemia-reperfusion injury

ischemia phase

• low blood flow, low O2

• cells do anaerobic resp = low ATP

• ion pumps fail (cell swells bc of Ca buildup)

reperfusion phase

• sudden O2 bursts = burst of reactive O2 species (cause redox reactions, which cause damage in other parts of cell)

• oxidative stress → ROS cause membrane damage and mitochondrial Ca overload

injury mechanism

• tissue transplantation

• ischemic syndromes (myocardial, hepatic, etc)

free radicals/ROS

• increase in reactive species

• detrimental oxidation of lipids (bad membrane, inc permeability, swelling, necrosis), proteins (enzyme inactivation, fragment proteins), and nucleic acids (gene mutations)

• mitchondrial effects

  • dysfunction bc of ROS

  • not enough antioxidants - they neutralize ROS

  • harm when ROS > antioxidants

chemical/toxic injury

• direct toxicity to the cell (direct exposure)

  • damage to and destruction of plasma membrane

• reactive free radicals and lipid peroxidation

  • lead - affects NS

  • CO - reduces O2 carrying capacity, promote tissue hypoxia

  • ethyl alcohol - nutritional deficiency (folate = need for folic acid)

  • mercury - affects NS, kidneys

cellular accumulations

cells catabolize “stored” substances that cause metabolite accumulation in cells

water

• cell swelling

lipids/carbs

• affect liver - fatty liver

glycogen

• in genetic disorders - glucose storage disease

• Von Gierke Disease - glucose 6-phosphatase deficiency; glycogen accumulates in liver/kidneys

uric acid

• causes gout

pathologic calcification (2 types)

abnormal deposition of Ca

dystrophic

• Ca deposits in dead/damaged tissue, but normal Ca levels (calcify plaque in arteries, can’t squeeze it out)

metastatic

• Ca deposition in normal tissue bc of increased Ca

2 types of cell death

necrosis

• uncontrolled death of cells/tissues in a living organism - caused by injury

• includes inflammation leading to autolysis

apoptosis

• no inflammation

• type I - programmed cell death (directly kill)

• type II - autophagic cell death (need help from other structures)

necrosis + process of it

sum of cell changes after local cell death + autolysis (autodigestion)

Process:

1) pyknosis

• nucleus shrinks (smaller, darker, denser)

2) karyorrhexis

• nucleus fragments (break DNA into pieces)

3) karyolysis

• nuclear dissolution + chromatin lysis

• enzymes digest DNA

• nucleus disappears

types of necrosis (5)

*based on morphologic appearance of dead tissue

• Coagulative

• liquefactive

• caseous

• fat

• gangrenous (3 types)

coagulative necrosis

• cells become gray, firm mass

• denaturation bc of activation of enzymes

• common in kidneys, heart, adrenal gland

liquefactive necrosis

• hydrolytic enzymes make fluid-filled cysts/form pus

• common in neurons/glial cells in brain

caseous necrosis

• cells transform into cheese-like substance that is walled off

• TB - cavities form in the lungs

• combo of coagulative and liquefactive necrosis

fat necrosis

• occurs in fat tissue

• common in breast, pancreas, abdomen

• action of lipases - break down lipids into fatty acids

gangrenous necrosis (3 types)

mass of tissue undergoes necrosis

• dry → tissue dries/shrinks, skin wrinkles, color goes brown → black (caused by big blood loss without significant bacterial infection)

• wet → when dead tissue becomes infected by bacteria - rapid tissue breakdown + swelling

• gas gangrene → special type from tissue infection (clostridium bacteria)

apoptosis

programmed cell death

• highly selective process, eliminates aged/injured cells, control tissue regeneration

• disregulated apoptosis is excessive/insufficient (cancer, autoimmune disorders, neurodegenerative disease, ischemic injury)

autophagy

self-eating

• self-destructive → cell digests its own damaged parts/old organelles/misfolded proteins to clean and make energy

• survival mechanism → damaged mitochondria can leak toxic ROS

• by digesting broken parts, autophagy acts as anti-aging - keep cells healthy/functional

aging + 2 major theories

aging is normal, inevitable, universal

• causes accumulation of damaged macromolecules

programmed theories

• aging follows biological schedule

• regulated by genes

• predetermine replication limits

damage/error theories

• aging bc of accumulated damage over time

• inc in free radical effects on cells

• structural alterations