Med I: Intro to Pathphysiology

Physiology

study of how it normally works (physio = nature/func)

Pathology

study of strucutal alternatives in cells, tissues, & organs that help ID cause of diease

what changes occured to cells/tissues/organs

Pathophysiology

disease caused what clinical effects?

study of functional change sin cells, tissues, & organs altered by disease and/or injury

etiology

study of cause(s) of disease &/or injury

Idiopathic

disease w/ no identifiable cause

Nosocomial

disease acquired as consequence of being in the hospital/ originate in healthcare

iatrogenic

disease and/or injury as result of medical intervention/treatment

clinical manifestation

Sx/s

signs

objective finding observed/ measured on physical examination

(temperature/pos. straight leg raise/ decrease visual acuity

symptoms

subjective findings pt experience/ reports

ex: chills/sore throat/ pain/ blurry vision

complications

additional unexpected problems as a result of disease/ treatmet

sequelae

residual effect of previous disease/injury

Nucleus

Control center! (DNA)

Contains nucleolus

Function:

• “instructions”

• cell division and control of genetic info

• replication and repair of DNA and transcription of info stored in DNA → RNA

Cytoplasm

aqueous solution that fills cytoplasmic matrix (1/2 volume of euk cell)

crowded w/ ribosome making proteins

Ribosomes

RNA- protein complexes → loca of RNA transcription (carries DNA’s message)

info from DNA (mRNA) to build proteins and provide sites for cellular protein synthesis

Endoplasmic Reticulum

Transportation syst of proteins and enzymes (make and process)(outer nuclear membrane)

RER: synthesis folding and transport of protein components

• move to memb…?

SER: synthesis of steroid hormones and ?? of variety of reactions to remove toxic compounds

• start processing proteins/lipids

Golgi Apparatus

networks of flattened smooth membrane and vesicles located near nucleus

packages and processes proteins into secretory vesicles that break away from golgi to intra- and extra- cellular destinations

packing system (UPS - stick label and ship out)

Lysosomes

sac-like; contain digestive enzymes to breakdown cellular components, bacteria, and foreign substances (into → amino acids, fatty acids, carbs)

Mitochondria

Power plant of cell~

extract energy from organic compounds (most ATP generated here!)

Plasma Membrane Function

Control composition of space/ components they enclose

via selective permeability - enable exclusion of molecules

Plasma Membrane Component: Functions of Plasma Membrane Proteins

It itself is a lipid bilayer! (lipid inside w/ -charged hydrophilic heads!)

Transport Channel: use for charged ions! (can’t go thru charged heads and nonpolarized tails)

Enzyme: catalyst

Cell Surface Receptor: ***drugs typically act here!!

Cell Surface Markers

Cell Adhesion

Attachment of cytoskeleton: keep shape/form of cell

Lipid Bilayer: embedded proteins and attached extracellular carbohydrates

Lipid: all lipids amphipathic (1pt hydrophobic other hydrophilic = 2layers)

• func: barrier to diffusion of water and hydrophilic substances while allowing lipid-soluble molecules (eg o2 co2) to diffuse readily

  • molecular glue (structural integrity)

• mains: phospholipids, cholesterol, glycolipids (w/ carb - cell recog)

Proteins: most of plasma membrane’s tasks; major workhorses of cell

• lots of membrane proteins

• Func:

  • recog and binding units (recptors) for substance in/out of cell

  • pores/transport channel (ions & specific carriers fo AA and monosacc)

  • cell surface markers (glycoproteins on carbs (cell recog)

  • cell adhedison molecules (CAM)

  • catalysts

Carbohydrates:short chains of sugars/carbs w/in plasma membrane’s tasks (mostly bound to glycoproteins and glycolipids)

• glycocalyx: all carbo on outside of plasma membrane + carb coating

  • help protect cell for mechanical damage

• Func:

  • cell-cell recog

  • adhesion

  • slimy surface → mobility of other cells thru narrow surfaces

Lipid Bilayer in Physiologic Conditions

1: Solid Gel Phase - L beta (only phospholipid bilayer)

2: Liquid-ordered Phase: L o (cholesterol and sphingolipid glycosphingolipid lipid)

3: Fluid liquid crystalline/ Liquid-disordered Phase: L alpha (disordered phospholipids w/ cholsterols)

Cell-to-Cell Communcation

Contact Signaling: via plasma membrane bound receptor

• signaling molecule from signaling cell accepted at receptor site on target cell

  • ex: fetal development

Remote signaling: via secreted molecules

• carrier protein transports small hydrophobic signal molecule which accepted by intracellular receptor protein in nucleus of target cell

Contact signaling: via gap junctions

• touch and move

  • typ of cardiac and neurons requiring electrical current communication and coordination

Cell Signaling

Neurotransmitter: nerve cell secretes neurotransmitters that are accepted by receptors on the target cell

Cell Signaling

Neurohomone secretion: neuron secretes neurohormones thru bloodstream and to target cell

Cell Signaling

Hormonal/Endocrine: source cell secretes receptors to target cell via bloodstream and stream

Cell Signaling

Autocrine: cell secretes receptors that bine to same cell (to itself)

Cell Signaling

Paracrine:source cell secretes receptors for target cells

Cell Signaling

Contact-Dependent: membrane signal molecule links the source cell and target cell

Plasma Membrane Receptors: Channel Linked Type

AKA ligand-gated channels: rapid synaptic signaling b/t electrically excitable cells

channels open/close briefly (neurotransmitters) → change ion permeability of plasma memb of post synaptic cell

Plasma Membrane Receptors: Catalytic Type

Activated by ligands; func as enzymes

Compostion: transmemb proteins

Plasma Membrane Receptors: G-Protein Linked Type

Indirectly activate/inactive plasma membrane enzyme/ion channel

Mediated by guanosine triphosphate (GTP) binding regu protein (G protein)

Activation: chain of reactions to alter concentration of intracellular messengers (cAMP/Ca/signaling molecules )

Active Cellular Intake

1: Coupled Pump: uphill transport of 1 solute to downhill transport of another solute

2: ATP-Driven Pump: drive uphill transport from hydrolysis of ATP

3: Light-Driven Pump: bacteria energy from sunlight to drive uphill tansport

Passive Transport: Diffusion

Solute molecules move from HIGH → LOW concentration

Passive Transport: Osmosis

Solvent molecules move from LOW → HIGH solute concentration

Type of Passive Diffsuion

Simple Diffusion: ready diffusion down concentration gradient (O2, N, urea, H2O, CO2, glycerol)

Channel-Mediated

Transporter-Mediated

macromolecules too large to diffuse

ions (can be repelled if line w/ same charge. no necessarily prevent diffusion but can slow down)

Filtration (Passive Diffusion)

Movement of water AND solutes thru membrane b/c of a greater pushing pressure/force on 1 side of the membrane (hydrostatic pressure)

• ex vasc system

Osmolality

measure of number of milliosmoles/kilogram (mOsm/kg) of H2O

AKA concentration of molecules per weight of water

Osmolarity

measure number os milliosmoles/liter (mOsm/L) of solution

AKA concentration of molecules per volume of solution

Osmotic Pressure

amount hydrostatic pressure req to oppose osmotic mvmt of water

factors: type and thickness of plasma memb, size of macromolecules, conc of molecules/cont gradient, solubility of molecules

Oncotic Pressure

overall osmotic effect of colloids (plasma proteins)

Tonicity

effective osmolatity of solution

(isotonic/hypertonic/hypotonic)

Isotonic

same osmolality/conc of particles

(~285 mOsm/kg for intra/extracellular fluid)

Hypertonic

COnc of >285-294mOsm/kg

Cell will shrink (more solute outside)

Hypotonic

Lower concentration (more dilute than body fluids <285mOsm/kg)

Cell will bloat (more solute inside)

Transport of Glucose

Transport Syst:

• passive: protein channel

• active: symport w/ Na+

Tissues: MOST

Transport of Amino Acids

Transport Systems:

• AA specific transporters: couple channels (intestines, kidney, liver)

• AA (except proline): Active symport w/ Na+ (liver)

• Specific AA: Active group translocation (small intestine)

Transport of Na+

Transport Systems: simple passive transport

Tissues: distal renal tubular cells

Transport of Na/H+

Transport Systems: active antiport; proton pump

Tissues: proximal renal tubular cells and small intestines

Transport of Na+/K+

Transport Systems: Active ATP driven protein channel

Tissues: plasma membrane!! (most)

Transport Ca2+

Transport Systems: ATP driven antiport w/ Na+

Tissues: ALL cells (antiport in RBC)

Transport of H+/K+

Transport Systems: Active

Tissues: Parietal cells of gastric cells secreting H+

Atrophy

response to DECR in work load/adverse envrionmental factor

→ smaller size and more efficient func

Hypertrophy

Incr in work load

→larger cell size and incr in functioning tissue mass

Hyperplasia

incr in number of cells in tissue/organ (only w/ cell capable of mitotic division)

Metaplasia

reversible change in which one cell type→replaces

• usually response to chronic irritation/inflammation (may be precancerous)

  • cont/persistent stress likely → cancer

Dysplasia

deranged cell growth (may be reversible)

→varied cell sizes, shapes, and organization

STRONG precursor to cancer

• require surgical removal

Cellular Injury (genetic)

alter cells nucleus and plasma membrane’s structure, shape, receptors, or transport mechanisms

Cellular Injury (Epigenetic)

Induction of mitotically heritable alterations in gene expression w/o changing DNA

Cellular Injury (Nutritional imbalances) SAME

Pathophysiologic cellular effects develop when nutrients are not consumed in diet and transported to body’s cells

OR when excessive amts of nutrients consumed and transported

Cellular Injury (Temp extremes) PHYSCIAL

Hypothermic: high intracellular sodium conc

• abrupt drops: vasoconstrictions, incr viscosity of blood → ischemic injury, infarction, necrosis

Hyperthermic: varies based on severity of extent/nature/intensity

Compressive waves of air/fluid followed by decr pressure: may collapse thorax, rupture internal solid organs, and cause widespread hemorrhage

• co2 and n normally dissolved in blood can precipitate from solution and form small bubbles (gas emboli) → hypoxic injury and pain

Cellular Injury (Illumination) RADIATION

Fluorescent/halogen lamps: harmful oxidative stress

UV light: skin cancer

Blue light: Induces ROS and s-opsin aggregation

Cellular Injury (mechanical stresses) PHYSICAL

Injury via physical impact/irritation:

• compression: perpendicular force

• tension: stretching force

• torsion: twisting force

• fluid shear forces: layers rubbing against each other

Cellular Injury (Noise)

Acute loud noise OR cumulative effects of var intensities/frequencies/duration

Cellular Injury (Chemical Injury)

drugs (overdose), lead, mercury

Cellular Injury (Biological Agents)

Viruses, Parasites, Bacteria

Mechanism of Intracellular Accumulations - abnormal metabolism

normal cell converts to fatty liver cell w/ accumulation of fat molecules

Mechanism of Intracellular Accumulations - Defect in protein folding, transport

protein mutation in normal cell results in accumulation of abnormal proteins w/in cell

Mechanism of Intracellular Accumulations - lack of enzymes

enzymes in normal cell balances w/ complex substate proportional to soluble products: no soluble products? endogenous material accum → lysosomal storage disease

Mechanism of Intracellular Accumulations - ingestion of indigestible materials

normal cell surrounded by indigestible materials. INGESTION → exogenous material accumulates w/in call

Physiologic Adaptive Changes

Normal response to internal/external stimuli help maintain homeostasis and support bodily function.

Pathophysiologic Adaptive Change

Abnormal changes in response to disease, injury, harmful conditions

Apoptosis

Normal cell death as a result of aging “programmed cell death”

• little-no inflammation; only few cells involved

disregulated: patholgic! either excessive/insufficent

• leades to cancer, autoimmune, neurodegen, ischemic injury

Necrosis

Pathological cell death - autolysis after death of entire organism

cell death in organ/tissue of still living person

Unregulated enzymatic destruction → loss of cell memb integrity → inflammatory response

• induced by injury

• large areas of contiguous cells involved

Manifestations of Cellular Injury - Fever

release of endogenous pyrogens (IL-1, TNF-α, prostaglandins) from bacteria or macrophages

acute inflammatory response

Manifestations of Cellular Injury - Increased HR

Incr in oxidative metabolic process FROM FEVER

Manifestations of Cellular Injury - Incr in leukocytes

aka leukocytosis

incr in total #WBC b/c infections (5k-9k/mm³ is NORMAL)

Manifestations of Cellular Injury - pain

various mech (release of bradykinins obstruction, pressure)

Manifestations of Cellular Injury - Lactate dehydrogenase

Released from RBC, liver, kidney, skeletal muscle

Manifestations of Cellular Injury - Creatinine kinase

Release for skeletal muscle, brain, heart