U1 medicine - intro to pathophysiology & cell bio

physiology

study of normal functions of the human body

pathology

study of structural change in cells, tissues and organs of the body that cause or are caused by disease

anatomic pathology

examination of organs and tissues (biopsies)

ex: autopsy, breast tissue biopsy, bone marrow biopsy, pap smear

clinical pathology

examinations of bodily fluids (chemistry panels, microbiology, cultures)

Ex: urine culture

immunology

study of the body's resistance to infectious disease

morphology

fundamental structure or form of cells, tissues, organisms

histology

the study of the microscopic structure of tissues, study of cells and extracellular matrix of body tissues using staining

pathophysiology

cellular and organ changes that occur with disease AND the effects of these changes have on total body function (physiology of altered health)

-study of the effects and symptoms of disease

CRUCIAL to fully understand disease concepts and causes and future implications

can help guide the history you take and the physical exam you do

provides background for prevention and treatment of diseases

often explains why clinical signs and symptoms occur

etiology

the study of the causes of diseases

ex: biologic agents (bacteria, viruses, fungi), physical forces (trauma, burns, radiation), chemical agents (poison, alcohol), hereditary factors, nutritional excess or deficit

Many diseases do NOT have a single cause but are typically caused by many factors

congenital

condition is present at birth

ex: spina bifida, down syndrome, cleft palate

acquired

conditioned is caused by events that occurred after birth

ex: Lupus, coronary artery disease, skin cancer, kidney cancer

iatrogenic

disease related to treatment/medical intervention (medical intervention)

ex: side effects of chemotherapy (nausea/hair loss), bowel perforation during surgery, allergic reaction to blood transfusion or medication, urinary tract infection from getting catheter placed

produced by a physician/medical provider (the unexpected results from a treatment prescribed by a physician)

idiopathic

condition where cause is unknown

ex: hives, IBS, scioliosis

nosocomial

hospital acquired infection, disease originating in a hospital setting

-ventilator associated pneumonia, catheter associated urinary tract infection (CAUTI), MRSA

pathogenesis

-the pattern of tissue changes associated with the development of a disease

-the process by which an infection leads to development of disease

-everything that happens from time exposed to time disease develops

ex: HPV exposure- can develop into cervical cancer over years, exposure to asbestos- can lead to mesothelioma 10-15 years later

Steps: exposure, adhesion, invasion, infection, transmission

1. Virus implants at entry site

2.Virus replicates

3. Virus spreads to target organs/disease sites

4. Spreads to sites of shedding virus into environment

symptoms

subjective findings

what a patient reports

-ex: pt complains of throat hurting, itchy eyes, fatigue, nausea, knee pain, chest pain, dizziness, headache, tinnitus, shortness of breath

signs

objective findings

what a provider sees

-ex: rash, hives, discharge from eyes, swelling, throat redness, fever, hypertension, tachycardia, wheezing, coughing, afib

disease

acute or chronic illness that one acquires or is born with that causes physiologic dysfunction in one or more body systems

Each disease has an etiology, pathogenesis, pattern of recognizable signs and symptoms, and diagnosis

prognosis

probable outcome and prospect of recovery from a disease.

typically discussed in terms of various treatment options

complications

adverse event during course of disease or treatment

unexpected event while the primary disease is present

acute, unexpected

Ex: hypertension causing a stroke

sequelae

result or consequence of previous disease or injury, something that persists afterwards

long term, expected

Ex: difficulty walking or talking after stroke

clinical manifestation

how the disease shows itself in a patient (signs and symptoms)

-patient complains of itchy eyes (symptoms), you see discharge (sign)

protoplasm

a colorless, jelly-like substance found inside cells in which elements such as proteins, fats, carbohydrates, mineral salts, and water are present

cell membrane

functions: protection, transport, helps maintain concentration gradients

components: (phospholipid bilayer) cholesterol, carbohydrates, glycoprotein, channel proteins

Insulin can help with concentration gradients

nucleus

control center of the cell, contains dna

nucleolus

location of rna transcription

mitochondria

powerhouse of the cell, organelle that is the site of ATP (energy) production

extracts energy from organic compounds

ribosomes

site of protein synthesis

er

transportation system of proteins and enzymes in the cell

lysosomes

digestive system of the cell, breakdown cellular components, bacteria, and foreign substances

golgi apparatus

packaging of enzymes, hormones in the cell

vacuole

a space or vesicle within the cytoplasm of a cell, enclosed by a membrane and typically containing fluid

functions: storage of fluid

plasma membrane

functions: protection and transport

-acts as a protector and separator for extra/intracellular components

-controls transport, hold and binds receptors for hormones/biologically active substances

-participates in the generation and conduction of electrical currents

-aids in the regulation of cell growth and proliferation

composed of the lipid bilayer: phospholipids, cholesterol, and glycoproteins.

lipids

lipid bilayer is the basic structure of the cell membrane

-individual lipid molecules diffuse readily throughout their own monolayer

-main lipids found in the membrane: phospholipids (most abundant), cholesterol, and glycolipids

-phospholipids: key for repairing the membrane.

proteins

scattered throughout the plasma membrane

-some as channels

-some as glycoproteins

-some as membrane proteins

-some serve as cell recognition or surface identity proteins, which mark a cell's identity so that it can be recognized by other cells

-some act as enzymes, or in cell adhesion between neighboring cells

carbohydrates

function in immune response in the plasma membrane

-distinctive cellular markers allowing for recognition

-helps detect foreign substances in the body

contact signaling

using plasma membrane bound receptors

-relies on direction interaction between the plasma membranes of adjacent cells

chemical signaling

"remote signaling by secreted molecules"

using carrier proteins and intracellular receptor proteins

neurotransmitters bind to chemically gated channel-linked receptors in nerve and muscle tissue

contact signaling

via gap junctions

-cell communication where cells are connected by protein channels called gap junctions

-allow for exchange of ions and small molecules

paracrine signaling

secreted molecules diffuse locally and trigger a response in neighboring cells

endocrine signaling

secreted molecules diffuse into the bloodstream and trigger responses in target cells anywhere in the body, to organs that may be far away

autocrine signaling

secreted molecules diffuse locally and trigger a response in the same cells that secrete them

tonicity

the ability of a surrounding solution to cause a cell to gain or lose water

the effective osmolarity of a solution

isotonic

same osmolarity or concentration of particles (about 285 mOsm/kg) as the intracellular fluid (ICF) or extracellular fluid (ECF)

-saline is approximately isotonic to blood stream, not a lot of fluid shift

hypertonic

concentration of more than 285-294 mOsm/kg

-putting volume into bloodstream, water rushes out of cell into bloodstream to dilute it, shrinking cell

hypotonic

lower concentration; more dilute than body fluids

-give somebody hypotonic solution then water given to patient rushes into cells and they get bigger

antiport system

Na+ moves out of cell and K+ moves into cell (against concentration gradient so uses energy)

-requires ATP

electrogenic

-electrical potential where inside of cell is more negative than outside

-for every 1 ATP molecule hydrolyzed, 3 molecules of Na+ are transported out of the cell and 2 molecules of K+ move into the cell

3 OUT 2 IN

endocytosis

process by which a cell takes material into the cell by infolding of the cell membrane

Internalizing process: section of the plasma membrane enfolds substances from outside the cell and invaginates and separates from the plasma membrane, forming an endocytic vesicle that moves inside the cell

exocytosis

process by which a cell releases large amounts of material, expells substance

resting membrane potential

potential difference in a resting neuron, about -70mv

-inside of cell is more negative than the outside

depolarization

Na+ channels open, rushes into cell

-membrane potential becomes positive

threshold potential

the critical level to which a membrane potential must be depolarized to initiate an action potential

repolarization

Period during which potassium ions diffuse out of the neuron, making the membrane potential more negative

hyperpolarization

membrane potential becomes more negative due to excess diffusion of potassium out of the neuron

refractory period

a period of inactivity after a neuron has fired

absolute and relative

relative refractory period

the period of time following an action potential, when it is possible, but difficult, for the neuron to fire a second action potential, due to the fact that the membrane is further from threshold potential (hyperpolarized)

absolute refractory period

time during which another action potential is impossible; limits maximal firing rate

hypopolarization

when the resting membrane potential is more negative than normal

passive diffusion

solute molecules move from high to low concentration

osmosis

solvent molecules move from low to high solute concentration

Clinical use- patient comes in dehydrated, blood becomes concentrated because not enough fluid or water, sodium is high

Treatment: fluids to get fluid back in bloodstream electrolytes shift

osmolality

-the measure of the number of milliosmoles per kilogram of water

-the concentration of molecules per weight of water

osmotic pressure

the amount of hydrostatic pressure required to oppose the osmotic movement of water

osmotic movement of water is from low to high

oncotic pressure

-the pressure of water to move, typically into the capillary, as the result of the presence of plasma proteins

-the tendency of water to move into the blood by osmosis as a result of the plasma proteins

-the overall osmotic effect of colloids, such as plasma proteins

atrophy

type of cell adaptation

physical response to decrease in workload or adverse environmental factor

body reverts to smaller size and more efficient functioning

hypertrophy

type of cell adaptation

increase in workload resulting in larger cell size and increase in functioning tissue mass

(not good in heart if too big, loses efficiency)

hyperplasia

increase in number of cells in tissue or organ

-only occurs in cells capable of mitotic division (often occurs in intestinal epithelium, epidermis/skin, glandular tissue)

-the enlargement of an organ or tissue because of an abnormal increase in the number of cells in the tissues

metaplasia

reversible change in which one cell type replaces another usually due to chronic irritation or inflammation

-may be precancerous (in trachea of cigarette smokers, cell change where cells go from stratified squamous cells to columnar epithelial cells which down the line may turn into cancer cells, gastric reflux cells can change in esophagus and stomach)

dysplasia

deranged cell growth that results in varied cell sizes, shapes, and organization

-may be reversible, strong precursor to cancer (dysplasia on a pap smear due to HPV first signs of cancer if not taken care of)

atp depletion

loss of mitochondrial ATP and decreased ATP synthesis

results include:

cellular swelling

decreased protein synthesis

decreased membrane transport

lipogenesis

--> all changes that contribute to loss of integrity of the plasma membrane

free radicals

reactive molecules causing cellular damage

-unstable molecules that cause biochemical aging, especially wrinkling and sagging of the skin

-causes oxidative stress, dna damage, lipid peroxidation, protein oxidation

calcium related

calcium can be an activator of apotosis and necrosis

necrosis: calcium overload overwhelms a cell's ability to maintain homeostasis, leading to cell swelling, rupture of the cell membrane, and the release of cellular contents, which can cause inflammation in the surrounding tissue

-damage to mitochondria, plasma membrane

cell damage

caused by

-physical agents (mechanical/electrical forces/extreme temperature)

-radiation (ionizing, UV, non ionizing)

-chemical (drugs, lead, mercury, food)

-biological agents (viruses, parasites, bacteria)

-nutritional deficits/excesses

reversible cell injury patterns

-cellular swelling: Impairment of sodium/potassium pump, usually result of hypoxic cell injury

-Fatty change (steatosis): more severe than cellular swelling, small vacuoles of fat disperse through the cytoplasm, usually indicates severe injury

necrosis

pathological death of a tissue still a part of the living organism

- Microscopic appearance is progressive destruction/cell death in an organ or tissue that is still part of a living person

-Unregulated/uncontrolled enzymatic destruction → loss of cell membrane integrity → inflammatory response

apoptosis is normal and regulated, more controlled

cytoplasm or nucleus

organelles of intracellular accumulation of water, lipids, carbs, proteins, pigaments, calcium, and urate

steatosis

abnormal fat accumulation, intracellular accumulation of triglycerides

atherosclerosis

condition in which fatty deposits called plaque build up on the inner walls of the arteries

dystrophic calcification in injured tissues

metastatic calcification

calcification of normal tissue; increased serum calcium or phosphorus

abnormal endogenous products

-genetic disorder replaces normal enzyme with abnormal

-errors in metabolism

-ex: tay sachs

--> lipids accumulate in brain leading to motor and mental breakdown and death due to impaired enzymes that are needed to metabolize lipids

exogenous products

accumulation of pigments, environmental agents accumulate that the cell cannot breakdown

ex: lead poisoning, tattoos

endogenous pigments

normal: accumulation of melanin in tanned skin

abnormal: excess of bilirubin indicates disease

atp depletion

loss of ATP and decreased ATP synthesis results in

-cellular swelling

-decreased protein synthesis

-decreased membrane transport

-lipogenesis

affect the integrity and structure of the plasma membrane

o2 and o2 derived free radicals

lack of o2 progresses cell injury in ischemia (reduced blood supply)

-activated o2 species (free radicals) cause destruction of cell membranes and cell structure

intracellular calcium and loss of ca2+ steady state

normally intracellular ca2+ is low

-ischemia and certain chemicals cause an increase in intracellular Ca2+

-as more Ca2+ enters cell, plasma membrane is damaged progressively

-mechanism of Ca2+: activates number of enzymes to cause damage to plasma membrane

defects in membrane permeability

early loss of selective membrane permeability found in all forms of cell injury

symptoms of cell damage

-fatigue/malaise

-loss of well being

-altered appetite

-fever

-leukocytosis (increased WBC)

-increased heart rate

-pain

necrosis

tissue death induced by injury

-surrounding inflammatory cells involved

-large inflammatory response

-large areas of contiguous cells involved

caseous necrosis

associated with tuberculosis, pulmonary infections

-combination of coagulative and liquefactive necrosis

-cheese-looking necrotic tissue

fat necrosis

fatty tissue broken down into fatty acids

occurs in breast, pancreas, other abdominal structures

lipases work to cleave fat

gangenous necrosis

massive death or necrosis of tissue caused by combination of ischemia and superimposed bacterial infection

-body tissue dies due to lack of blood supply or bacteria infection

-classified as dry/wet/gas

-skin discoloration

coagulative necrosis

cell proteins are altered or denatured

changes protein albumin

occurs in kidneys, heart, adrenal glands

liquefactive necrosis

commonly results from ischemic injury to nerves and glial cells in brain

-injured cells release hydrolases that digests brain tissue; tissue becomes soft, liquefies, and segregates, forming cysts

-hydrolytic enzymes form liquid filled cyst or form pus

-may be caused by staph, strep, or E. coli infections.

apoptosis

-genetically triggered, normal cell process or pathological

-little to no inflammatory response

-only a few scattered cells involved

-programmed cell death

-dysregulated apoptosis can lead to cancer, autoimmune disease, neurodegenerative diseases, ischemic injury