3/28/2022

Lots of parts of our body systems work with a negative feedback loop

A negative feedback loop is a reaction that causes a decrease in function.

It occurs in response to some kind of stimulus. Often, it causes the output of
a system to be lessened; so, the feedback tends to stabilize the system. This
can be referred to as homeostasis, as in biology, or equilibrium, as in
mechanics. FUNCTIONS TO REDUCE THE CHANGE
 Thermoregulation (if body temperature changes, mechanisms are induced to
restore normal levels)
 Blood sugar regulation (insulin lowers blood glucose when levels are high ;
glucagon raises blood glucose when levels are low)

A positive feedback mechanism or positive feedback homeostasis is a

pathway that, in response to an output variation, causes the output
to vary even more in the direction of the initial deviation. A positive
feedback system amplifies deviations and causes output state changes.
FUNCTIONS TO AMPLIFY THE CHANGE
Positive feedback loop = pregnancy (stretching of uterine walls cause contractions that further
stretch the walls (this continues until birthing occurs), Ovulation – the dominant follicle releases
estrogen which stimulates LH and FSH release to promote further follicular growth

Stress
 Stress can be real or perceived and that threatens homeostasis
 Result is actual physical and/or mental tension
- Fight or flight SNS response
 Done everything to fix stressor
Fight or and you’ve exhausted everything
flight

How the SNS is activated

• Sense real or perceived threat
• Body goes from Ready Reactive
• Mobilize resources for energy for increase in cellular processes to meet body’s needs
• Epinephrine binds to adrenergic receptors throughout the body
Alarm phase
• “Fight or Flight” response
• Sympathetic-adrenal-medullary system
• Hypothalamic-pituitary-axis (HPA)
• Arousal
• Alertness
• Vigilance
• Cognition
• Focused attention
• Appropriate aggression
Neuroendocrine response
• Hormones:
• Catecholamines (epinephrine and norepinephrine; decrease insulin and increase
glucagon) IN THE ADRENAL MEDULLA
• CRF
• ACTH
• Glucocorticoids
• Mineralocorticoids
• ADH (antidiuretic hormone; increases water absorption)
Resistance
• AKA Adaptation Stage
• Goal is return to homeostasis
 • Many resources to help the body adapt
• Stressor resolved  homeostasis vs. allostasis (process of trying to get back to
homeostasis)
• May have a new baseline or “set-point” to maintain balance
• But what if the stressor is not resolved?
Exhaustion
• Prolonged exposure to stress
• Adaptive stores depleted
• Stress response itself
• Body no longer able to return to homeostasis
• “Allostatic Overload”
• Disease (headaches, insomnia, etc.)
DISEASE = EXHAUSTION

What influences our stress responses?

Ex: more RBC than you need

Gradual introduction rather

than boom

Ppl w sickle cell can help fight malaria

As we age we have less physiologic reserve, elderly and really young have more issues

Healthy ppl have more reserve

Bad nutrition for long periods of time messes with physiologic

reserve
Circadian rhythm, sleep restores things

Good social support, respond better to stress

The Body is Flexible: Adaptation Mechanisms

• Physiologic reserve—the ability of body systems to increase their function given the
need to adapt
• Red blood cells and oxygen
• Liver cells and nutrient storage
• Bone and calcium storage (calcium important for heart)
 • Anatomic reserve—paired organs that are not needed to ensure the continued existence
and maintenance of the internal environment
• Lungs, kidneys, and adrenals
Effects of Chronic Stress
• Pathophysiologic changes occur
• Illness and Disease
• Altered physiological function
• Cardiovascular, gastrointestinal, immune, neurologic systems
• Altered psychological factors
• Depression, accidents, suicide, chronic alcoholism, drug abuse, eating disorders
Don’t need
to memorize
LOL
3/30/2022
Cell Pathology
Normal cell

Shrinking bc of lack of activity

Less workload = smaller size
Ex: bedridden

Increased cell size, typically bc of an increase in workload

Can be good or bad
Good: if you lose one kidney the other will hypertrophy
Bad: high blood pressure and the heart muscle hypertrophy

Increases the number of cells

Can be good or bad
Good: cut in skin, more cells come to heal
Bad: wart (which is reaction to virus)

One cell changes itself for another cell

EX: long term smokers and irritation in
trachea and lining cells adapt to deal

Deranged cell growth

Precursor to cancer
REVERSIBLE
 Irreversible
• Mechanisms of Cell Injury
• Physical agents
- Extremes in temperature
• Radiation
- Sunlight, X-ray
• Chemicals
- Lead (toxic to brain cells, irreversible, very bad for kids)
• Biologic agents
- Virus (HIV, HPV)
• Nutritional imbalance
- Overnutrition and undernutrition
• Free Radicals
- Too much may be a problem with ALS, radiation causes more free radicals
• Hypoxia
- If oxygen doesn’t go to tissues, those tissues will die. EX: drowning can cause
hypoxia
• Impaired Calcium Homeostasis
- Calcium can accumulate if its offbalance, happens more in elderly
• Genetic mutations
- EX: down syndrome has huge link with leukemia, something in genetic makeup mkes
that cell injury prevelant
Neoplasia (THINK CANCER)
- Deranged, uncontrolled growth
- Neoplasia= New Growth
o Neoplasm= abnormal mass or tissue where growth>normal tissues
  Do not obey laws of normal cell growth
 Not useful
 Continue to grow at expense of host
- Classified as benign vs malignant

Can cause death, depends on

location (like if it’s on your
Less differentiated: when you come
brain stem)
from parent cell, you mutate, and
continues down the line
Well differentiated: look like
Leaves original site and goes
mom and dad; as I come from
somewhere else
parent cell, I look like parent
cell

Genetic Mechanisms of Cancer

Proto-oncogenes
• Normally have code for cell growth
 • Growth factors, receptors, signaling molecules, transcription factors
• Cause problem when overactive
• Too much growth
• Mutation
• Proto-oncogenes turn into Oncogenes (allow cells to continue to grow)
Tumor suppressor genes
• Normally prevent cell division
• Inhibit proliferation
• Repair DNA
• Induce apoptosis when cells are defective
• Cause problem when underactive
• Genetic screening
• Ex. BRCA
How Normal Cells Transform to Cancer Cells
• Called “Carcinogenesis”
• Initiation
- Damage
• Promotion
- Oncogenes
• Progression
- Tumor
• Etiology
• Not a single disease so not a single cause
• Interactions of multiple risk factors or repeated exposure to carcinogenic agent

Host and Environmental Factors Leading to Cancer

• Heredity
• Hormones
 - Different hormones affect different types of cancer and you cant change that
• Carcinogens
• Chemical
• Radiation
• Oncogenic viruses
- HPV
• Immunologic mechanisms
- If your immune system isn’t functioning properly, higher risk of certain cancers
• Stem cells
• Angiogenesis
• Angiogenic factor production or loss of angiogenic inhibitors
• There are some cancers that can travel to some part of your body, stay there and
get its own blood supply
• Microenvironmental effects
• Multiple cell types, cytokines, and growth factors
Risk Factors
• Cancer= 2nd leading cause of death in the US
• Lifestyle risks:
• Tobacco
• Nutrition
• Obesity
• Sun exposure
• Sexual exposure
• Screening important to catch early
4/4/22
Fluid and electrolyte balance: How the body regulates extracellular fluid volume, body fluid
osmolality, and plasma concentration of electrolytes
- Conceptually: “optimal balance/just right”, “too much” or “too little”
Body compartments
• Intracellular (fluid within cells)
• 2/3 body fluids in adults
• Electrolyte Distribution
• Extracellular
• 1/3 body fluids
• Electrolyte Distribution
Purpose
• Electrolytes
• impact cell function
• maintained within range primarily by kidneys
• present inside and outside cells
• Body Fluid
• surrounds and permeates the cells
• present inside and outside cells
• lubricates and hydrates cells for various functions
• transports oxygen, nutrients, and waste products important in regulating body
temperature
• cells need everything within balance for them to work
Homeostasis
• Dynamic interplay between three processes:
• Intake and absorption:
• Intake: addition of F&E to the body
• Absorption: movement into the blood
• Distribution:
• Process of moving fluid between compartments (Plasma Interstitium
ICF)
• Excretion/Output:
• Removal of F&E from the body via normal or abnormal routes
Body fluid: intake and absorption
Entry of fluid/electrolytes into body…
• Oral
• Metabolism
• IV
• Gastrointestinal (tube feeds)
• Bone marrow (makes our blood cells)
• Subcutaneous route (can be absorption)
Intake
 Thirst
- conscious sensation of the need to obtain and drink fluids
- often the result of a habit or other reasons
- most people drink without beinf thirsty
- thirst is basically an emergency response and occurs when the need for water has not
been anticipated
 Two stimuli for true thirst
• - Cellular dehydration caused by increased ECF osmolarity
• Decreased blood volume
• Increased levels of angiotensin II
 Thirst sensation from a dry mouth from a lecturer, mouth breather, smoker and people
with chronic respiratory conditions is not necessarily associated with hydration status
 Thirst sensation decreases with age
 Body fluid: distribution
• Avg. 60% of body weight is water (fluid)
• Varies with gender, age and proportion of body fat
• Age-related alterations (infants)
• 1L of water = 1 kg (2.2 lbs)
• Ppl with more body fat have less body water
• Infants are 70-80% water because they have a lot less fat
EX: If one weighs 154 lbs (70 kg) - has approx. 42 L of fluid (70 L X 60% = 42L)
Intracellular water (2/3) – Approx. 28L
Extracellular water (1/3) - Approx. 14L
• Interstitium, Vascular, Transcellular fluid: synovial, cerebrospinal, GI fluids
Movement of fluid:
• Occurs via filtration process along a pressure gradient
• Hydrostatic Pressure (HP) (filtration pressure)
• Influenced by blood pressure and volume
• Pushes fluid out of capillary
• Colloidal Osmotic Pressure (COP)
• Exerted by plasma proteins (albumin)
• Draws fluid back into capillary
• Balance OR movement of fluid in or out of vasculature depends on the difference of the
opposing forces in the capillaries
Distribution example: edema
• Excess fluid in interstitium
• Why?
• Decreased capillary colloid pressure (loss of plasma proteins allows fluids to leak
out; examples are burns)
• Increased capillary hydrostatic (filtration) pressure (happens where there is a
venous obstraction, like wearing tight socks)
• Increased Capillary Permeability (happens with some types of disease states like
allergic reactions)
• Blockage of lymphatic drainage (normally its absorbed but after mastectomies it
sometimes happens)
• Result: Net movement of fluid out of vascular space into intersitium
Distribution of body fluid:
• Between Intracellular and Extracellular
• Cell membranes permeable to water and not electrolytes
• Difference in osmolality (particle concentration) of the two sides determines if
water moves inside or outside of cell
Osmolaity
Osmolality : “Concentration of molecules per weight of water”
“Number of dissolved particles per unit of water”
• When the amount of water decreases in relation to # particles, the osmolality increases
and becomes concentrated
 • When the amount of water increases relative to solutes the osmolality decreases and
becomes more diluted
• The primary particle responsible for regulating osmolality is sodium
• Where sodium goes, water follows
Hyponatremia
• Low sodium in ECF (extracellular fluid)
• Therefore decreased osmolality of ECF
• Therefore ECF less concentrated (hypotonic)
• Sodium and Water: A love story
• Water moves FROM where there is low sodium concentration (high water
concentration) TO where there is higher sodium concentration
• Water moves into cell – expands (swells)
Hypernatremia (increased osmolality in ECF)
• High Sodium in ECF
• Therefore increased osmolality in ECF
• Therefore ECF more concentrated (hypertonic)
• Sodium and Water: A love story
• Water moves FROM where there is high water concentration low sodium
concentration (high water concentration) TO where there is high sodium
concentration
• Water moves out of cell - shrinks
Isotonic is BALANCE
• Osmolality stable – same concentration as vascular compartment
• No cellular change
• Usually no change in electrolyte level
• Volume levels can change (excess or deficit) – which may cause other issues such as
edema or shock
Hyper-osmolality: cells shrinking – cell dehydration
Hypo-osmolality: cells swelling – cell water gain
Body fluid: excretion
Normal Excretory Routes:
• Kidneys
• Skin
• Sensible Perspiration
• Insensible Perspiration
• Lungs
• Gastrointestinal Tract
Abnormal Excretory Routes:
• Emesis (consistent vomiting)
• Hemorrhage
• Drainage (fistulas, tubes etc.)
• Paracentesis (drain fluid out of abdomen)
Excretion: Urinary through kidneys
• Controlled by
 • ADH (antidiuretic hormone)
• Aldosterone
• Natriuretic peptide
*Dependent on adequate BP to perfuse kidneys and on the GFR

This is what body does when it

senses that blood is more
concentrated

• Factors that decrease ADH release:

• Alcohol [increased urination]
• Decreased Osmolality (concentration)
• Increased Circulating Volume [body senses theres enough blood volume so you
don’t need to hold on to more water]
• DI
• Factors that increase ADH release:
• Increased osmolality (concentration)
• Decreased circulating volume
• Stress
• SIADH [syndrome of inappropriate diuretic hormone]
Urinary aldosterone
• Released as part of RAAS
• Renin-angiotensin-aldosterone system
• Low flow to kidneys stimulates this cascade to help us hold onto more volume
• Aldosterone
• Causes us to retain sodium and excrete potassium
• Sodium and water: A love story
• Retaining sodium causes us to retain water (and therefore volume)
Result: Increased fluid volume means increased BP
Urinary natriuretic peptides: naturally occurring peptides that help with fluid volume
• Atrial natriurectic peptide (ANP)
• Released when atria stretched
 • Brain natriurectic peptide (BNP)
• Released from ventricular cells when ventricular pressure increased abnormally
(HF)
• Indicates heart failure
• ANP and BNP release causes natriuresis and diuresis
• Increase glomerular filtration rate and inhibit tubular sodium and water
resorption
• Inhibit the SNS resulting in vasodilation and decreased preload
• Inhibit the RAAS reducing renal fluid retention
• Affect CNS and brain inhibit secretion of ADH
Electrolytes: intake and absorption
Intake:
• Occurs via food and fluids
• Oral Medications can contain electrolytes
• IV Solutions
• Blood transfusions
• Rare occurrences: near drowning, NGT/GT feedings
• Monitor electrolytes and then replace as needed
• Absorption: Depend on…
• Concentration gradients
• GI contents (excessive vomiting, excessive diarrhea)
• Other substances such as Vitamin D
• Medications

Excessive urination
Sweat has to be pretty excessive
If stool is excessively liquid you loose
more electrolytes
Abnormal routes would be drains, tubes,
wounds; burn patients leak a ton of fluids
Electrolyte Normal Values and Core Functions: KNOW THESE
Sodium (Na+) 135 - 145 mEq/L
Chloride (Cl-) 97 - 107 mEq/L
Potassium (K+) 3.5 - 5.0 mEq/L
Calcium (Ca++) 8.2 - 10.2 mg/dL
Phosphorus (PO4-) 2.5 - 4.5 mg/dL
Magnesium (Mg++) 1.6 - 2.6 mg/dL
Bicarbonate (HCO3-) 22 - 26 mEq/L

Acid Base Balance

Homeostasis
• Ph needs to be within a certain range in the body (7.35-7.45)
• If not, enzymes and metabolic functions will not work
• The body regulates ph through balancing acid and base
• Acid production/intake
o Products of cellular metabolism
o Generates carbonic acid (H2CO3) and metabolic acids
o Intake: Entry of acids into body or substances that convert to acids
• Acid buffering
o Body fluids resist changes in pH when acid or bases are added or
removed
 o Take up H+ or release H+ to keep pH in normal range
• Acid excretion
o Removal of acid from body
o Lungs excrete carbonic acid
o Kidneys excrete metabolic acids
pH
• pH reflect acidity or alkalinity
• Best way to measure is via arterial blood gases (ABG)
• H+ concentration measured in terms of pH
• Increased H+ ions – decrease pH
• Decreased H+ ions – increase pH

• Three major mechanisms regulate acid-base status of body.

• Buffers
• Respiratory system (Lungs) (CO2)
• Renal system (kidney) (HCO3-)

• If too much acid; too many Hydrogen ions

• Acidic
• Low pH
• Bicarbonate ions take up hydrogen ions (H+) from the acid; become carbonic acid
 • Carbonic acid released as carbon dioxide through the lungs
• Lungs blow off CO2 to increase pH
• H+ + HCO3- = H2CO3 = CO2 + H2O
• If too little acid; not enough Hydrogen ions
• Alkaline
• Elevated pH
• Bicarbonate buffer releases hydrogen ions to decrease pH (make more acidic)
• H2CO3 = H+ + HCO3-
nd
2 line of ph regulation: lungs
Respiratory regulation
• Very large surface are from which CO2 can diffuse
• When we breathe out, we breathe out CO2 and water
• This removes carbonic acid (H2CO3) from the body
• Removal of CO2 from the body can be a response to increases in H+ concentration
(acidic ph)
• Hyperventilation: CO2 is “blown off”
• CO2 has the most profound effect on respirations (except for chronic patients)
• Respiratory response to correct ph:
• Begins in minutes
• Requires at least several hours for full effectiveness
• Not long-lasting (not a permanent fix)
• How does our body regulate the rate and depth of respirations in response to pH?
• Chemoreceptors in the brain sense PaCO2 (arterial CO2 concentrations) and pH
of blood
• Body alters respirations accordingly
• How does the body do this?
• If too much carbonic acid (too much CO2/too acidic)
• Body increases rate and depth of respiration
• Excess carbonic acid/CO2 removed to increase pH (blow off CO2)
• If not enough carbonic acid (too alkaline)
• Body decreases respiratory rate and depth
• Allows for temporary accumulation of carbonic acid/CO2 to decrease pH
rd
3 line of pH regulation: kidneys
 • Can excrete any acid from the body except carbonic acid (solely excreted by the lungs)
• Kidneys have to be functioning properly for this to work
• Works slowly
• Several days
• Powerful and efficient
• One of major functions
• HCO3- regulation
• Can assist with compensating for abnormal carbonic acid levels:
• For high carbonic acid levels
• Increase the excretion of metabolic acids and H+
• Retain HCO3-
• For low carbonic acid levels
• Decrease the excretion of metabolic acids and H+
• Excrete HCO3−

High CO2 makes you: acidotic

Low CO2 makes you: alkalotic
High Bicarb: alkalotic
Low Bicarb: acidotic

Acid-Base Imbalance
Acidosis
• Low pH (<7.35)
• High H+ concentration
• HCO3- below normal
Alkalosis
• High pH (>7.45)
• Low H+ concentration
• HCO3- above normal
If youre not breathing then you retain CO@ and youre acidotic

Inflammation
3 lines of defense

Barriers:
• Physical
• Intact barriers!
• Skin & mucous membranes
• Skin epithelium
• Intestinal epithelium
• Goblet cells
• Tight junctions
• Mechanical
 • Cilia (traps stuff in your lungs so you can cough it uo)
• Cell turnover
• Coughing, sneezing, urinating
• Biochemical
• Epithelial-derived chemicals
• Skin epithelium
• Intestinal epithelium
• Perspiration
• Sebaceous glands
• pH of skin surface
• Goblet cells
• Mucous
• Saliva
• Tears
• Earwax
• Lungs
Inflammation
• Pathologic and physiologic responses intended to eliminate the initial cause of cell
injury, remove damaged tissue, and generate new tissue
• Accomplished by
• Destruction
• Enzymatic digestion
• Wall off
• Neutralization
• Activated by cell or tissue damage
• Rapid response
• Nonspecific
• Vascularized tissues (need good blood flow)
• Humoral and cellular interaction
What does inflammation look like?
• Local
• Redness
• Swelling
• Heat
• Pain
• Loss of function (depends on the degree of inflammation)
• Systemic
• Fever
• Leukocytosis
• Increase in circulating plasma proteins
• SIRS (more about this soon!) [sepsis]
Systemic response to inflammation: more WBC and maybe fever, increase in circulating plasma
protein
 Inflammatory phases

Exudate = drainage
from the wound

EX: foreign body stuck

inside you

Acute inflammation has vascular stage and cellular stage

swelling
Vascular response patterns

Anything with -itis at the end is an inflammatory response

Cellular response
• Many cells and tissues are involved in the inflammatory response
• Endothelial cells
• Leukocytes (WBCs)
• Connective tissue cells
• ECM (extracellular matrix)
• Collagen
• Elastin
• Cells involved
Endothelial cells – cell thick lining of blood vessels
Circulating WBCs (leukocytes)
Two types of leukocytes participate in the acute inflammatory response:
o Granulocytes (neutrophils, eosinophils, and basophils)
o Monocytes (the largest of the white blood cells)
Connective tissue cells
Components of extracellular matrix -- collagen, elastin
Marked by movement of phagocytic white blood cells (leukocytes) into the area of
injury
Leukocytes (WBC)

More about neutrophils:

• Chemotactic factors attract neutrophils to areas of inflammation and bacterial products
• Neutrophilia
• Increase in circulating neutrophils
• Neutropenia
• Decrease in circulating neutrophils
• Shift to the left or bandemia
• When there is an excessive demand for phagocytes immature forms of
neutrophils are released called bands
• Body cant keep up with demand for WBC so the body releases immature ones
• Neutrophils release toxins
• Can damage normal tissue
• Usually not a problem if you’re healthy
Inflammation associated with immediate hypersensitivity
Histamine: vasoactive, vasodilates
Cytokines: are like the messenger,
communicate between the
different responses
Arachidonic acid metabolite
Platelet-activating factor: first
piece of clotting
Plasma proteins: affect the
compliment system, clotting
system

Inflammatory mediators

Serous Exudates
Watery fluids low in protein content
Result from plasma entering the inflammatory site
Hemorrhagic Exudates
Occur when there is severe tissue injury that causes damage to blood vessels or when there is
significant leakage of red cells from the capillaries
Membranous or Pseudomembranous Exudates
Develop on mucous membrane surfaces
Are composed of necrotic cells enmeshed in a fibropurulent exudate
Purulent or Suppurative Exudates
Contain pus; composed of degraded white blood cells, proteins, and tissue debris
Fibrinous Exudates
Contain large amounts of fibrinogen and form a thick and sticky meshwork
4/11/22
Infection and Infectious Diseases
Agents of infectious disease “pathogens”
• Prion
• Transmitted neuro-denerative disease –EX: mad cow
• Hard to get transmitted, hard to get into somebody, but it is incredibly hard to
treat
• Viruses
• No organized cell structure
• Incapable of replication outside of living cell
• Can survive outside of host and spread – ie flu, RSV
• Bacteria
• Have to know what it is in order to treat it
• Manner which divides helps identify – cluster/chain
• Gram stain – positive or negative – helps determine treatment
• Sensitivity sees which antibiotic will actually kill it
• Refers to color of stain and cell walls of the bacteria
• Gram + cell walls retain dye and appear violet
• Gram – cell walls lose color and appear red
• Can have motility – spirochetes – Lyme disease
• Mycoplasmas
• Unicellular prokaryotes (single celled organism that has neither a distinct nucleus
with a membrane nor other specialized organelles) capable of independent
replication
• Typically see them in pneumonia, not incredibly common
• Ricketssiae, chlamydiae, ehrlichieae, coxiella
• Need living cell (like virus) but have RNA/DNA like a bacteria
• Rocky Mountain Spotted Fever
• Fungi
• Yeasts and molds
• Can be normal part of flora
• Parasites
• Helminths – worms
• Arthropods – scabies and lice
Bacteria
• Classified by genus and species (e.g., Escherichia coli, Staphylococcus aureus)
• Live in colonies
• Biofilms = BAD
 • Structured communities
• Access to nutrients and elimination of waste
• Covering that protects from antibiotics
• Clusters/pairs/chains
• How they divide
• Described by:
• Morphological appearance (e.g., diplococci)
• Ability to thrive in oxygen-rich environments (i.e., aerobic bacteria) or oxygen-
free environments (i.e., anaerobic bacteria)
• Appearance upon manipulation, including lab staining (e.g., gram positive versus
gram negative)
Bacterial infections
• How sick will the host become once infected? Depends upon:
• Host immunocompetence (is their immune system fully functioning?)
• Bacterial virulence (how hardy and hard to get rid of is this bacteria):
• Exotoxins
• Can inactivate or modify key aspects of host cell structure or
function
• Example – botulism inhibits neurotransmission – paralysis (also
botox LOL)
• Endotoxins
• Lipopolysaccharides (LPS) found in cell wall of gram negative
bacteria
• Negative effect on immune system ability; impedes its ability to
fight it
• High levels of LPS can precipitate DIC
• Receptor & ligand affinity
• Mechanical strength of adhesion
• Embed with protective film
• Anchor and protect itself from host defense
Transmission of pathogens
• Direct contact (I come up to you and cough and sneeze on you)
• Indirect transmission:
• Vectors
• Biting insect - tick
• Congenital/vertical
• Placental/birth
• Portal of entry:
• Injection/penetration
• Break skin
• Ingestion (swallow)
• Inhalation
The chain of infection WASH UR HANDS
• Pathogen/Infectious agent
 • Reservoir
• Portal of exit
• Means of transmission
• Portal of entry
• Susceptible host
Pathogens: classified y source of transmission
• Hospital-associated/Hospital-acquired (formerly nosocomial)
The person came into hospital without the infection, and you gave it to them somehow
• Community-associated/Community-acquired
Acquired in the community
• Opportunistic
• Host immune system compromised – HIV/AIDS
• Cancer patients also
• The hosts immune system is so bad
Diagnostics
• Clinical manifestations
• Clinical history (history and physical exam are the most important)
• Complete blood count
• White blood cell count (WBCs) if its elevated -> something infectious, really good
indicator of disease
• WBC differential (i.e., “diff”)
• Bacterial Infections:
• Gram Stain
• Culture & Sensitivity (C&S)
• Viral Infections:
• Antibody titers
• Can check if serum antibodies present
• Not definitive, just point in direction
• Polymerase chain reaction (PCR)
• DNA detection of a pathogen (LYME)
Treatment of infectious disease
• Prevention!
• Immunization
• Quarantine
• Hand hygiene
• Eradicate the pathogen, if possible:
• Pharmacologics:
• Antibiotics for bacterial infections
• Antivirals for viral agents
• Incision & drainage of infected abscesses
• If eradication of the pathogen is not possible (e.g., viruses):
• Minimize/control its ability to replicate &/or diminish its virulence:
• Pharmacologically
• Immunomodulation
 • Help control immune system response
• Decrease inflammation for example
Immune responses and disorders of immunity
Purpose of immune system is to know the difference between self and non-self
The first cells that respond to an acute injury are the neutrophils
Properties of the immune response
• Natural Immunity
• Also called innate immunity
• In place before infection and can function immediately
• Skin and mucous membranes (want to get rid of it before it gets in the body)
• Neutrophils, macrophages, natural killer cells
• Acquired Immunity
• Also called adaptive
• Respond to antigens (foreign things coming in)
• Humoral [throughout your entire body] (B lymphocytes) and Cell-mediated
immunity [only at the cell level] (T lymphocytes)
• B -> entire Body T -> only aT cell level
Essential cooperative interaction between the two 
• Specificity – adaptive immune system can develop a unique specific immune response
for a substance; can recognize and attack
• Diversity – can respond to millions of different kinds of antigens – enormous variety of
lymphocytes (adaptive)
• Memory – repeat exposure to the same microbe or agent produces a quicker and more
vigorous response from the adaptive immune system; immunizations are memory for
your body
• Self vs Non-self – innate recognizes and reacts to non-self
• Pathogen Recognition
• Innate Immunity
• Recognize molecules that are normal components of microbes but not
host cells
• Some recognition = phagocytosis
• Some recognition = initiation of adaptive immune response
• Adaptive Immunity (what you have in body isnt enough)
• Antigens are foreign substances to the host
• These foreign molecules are recognized by receptors on immune cells
called antibodies that are made in response to antigens
Antigens – stimuli of the immune system
• Foreign macromolecules
• Proteins
• Polysaccharides
• Lipids
• Nucleic acids
• Immunologically active sites on antigens – epitopes
 • Unique molecular shape of the epitope recognized by a specific receptor on the
surface of a lymphocyte or by an antigen-binding site of a secreted antibody
4/13/22
Pathogens are the germs
Antigens are the parts in your body that tells your body “I don’t belong”
Antigens stimulate:
• Antigen-presenting cells; hang around sense something that doesn’t belong and eat it;
purpose is to get it and try to get rid of it
• Macrophages; eat it and then present it
• Dendritic cells; they
• T cells (MHC) – Cell-Mediated Immunity
• Helper T cells – CD4+
u Activation depends on recognition of antigen
u Master regulators of the immune system; they have a lot of power
u Once activated secrete cytokines (chemicals that go out in body that
influence other cells) that influence function of nearly all other cells of
the immune system
u AIDS hurts the CD4 and CD8
u “Master switch”
u Secrete cytokines
B cells:
Cytotoxic T cells:
Natural killer (NK) cells
• Cytotoxic T cells – CD8+
u Helper T cells activate cytotoxic T cells
u Perform killing function by injecting cytotoxic protein into target cell
triggering apoptosis (cant replicate)
• B cells – Humoral Immunity
• Plasma cells
• Immunoglobulins (i.e., antibodies)
Cell-mediated immunity
• Cytotoxicity
• Targets cell for apoptosis
• Delayed hypersensitivity
• Responding to soluble protein antigens and T cell response require synthesis of
effector molecules that takes 24-72 hours to develop
• TB test
• Memory
• Subsequent exposure rise in antibodies will occur sooner
• Control (if they’re not turning on and off properly then you have autoimmune disorder)
• CD4 controls and coordinates host defense
Antigens stimulate:
• B cells – Humoral Immunity (means throughout the body)
• Plasma cells
 • Immunoglobulins (i.e., antibodies)
• Humoral immunity is mediated by antibodies
• Antibodies are borrowed, they don’t change our immune system, only
work for the time they are in your bloodstream
Classes of Immunoglobulin
• IgG
• Most abundant, crosses placenta [mother baby transition]
• Protects against bacteria, viruses, toxins
• IgA
• Primary defense against local infections
• Found in saliva, tears, bronchial and GI secretions
• IgM
• First circulating antibody to appear in response to an antigen
• IgD
• Found primarily on cell membranes of B lymphocytes
• IgE
• Inflammation, allergic responses, parasitic infections
Humoral immunity
Combination of antigen with antibody can result in several responses:
• Neutralize bacterial toxins
• Opsonize bacteria – target for destruction
• Neutralize viruses – block binding sites
• Facilitation of phagocytosis
• Activation of complement cascade (inflammation)
• Assists in localizing and destroying infectious pathogens
Cardinal signs of Inflammation = heat, swelling, pain
Hypersensitivity means my immune system is reacting in a way that is too much than it should
be (that is what allergic reactions and allergies are)
-body can have memory of this reaction and make it worse next time
HIV/AIDS
• HIV: human retrovirus that infects CD4+ cells, leading to AIDS:
• CD4+ counts < 200 cells/mm3
• Opportunistic infections
• Opportunistic malignancies
• Dementia (AidsDementiaComplex)
• HIV enters brain and damages nerve cells
• Wasting syndrome (likes to replicate in the GI system and can affect that)
• Weight loss and diarrhea
HIV Transmission
• Sexual
• Blood borne
• Perinatal
WBC -> Leukocytes
• Types
 • Granulocytes
• Neutrophils
• Eosinophils
• Basophils
• Agranulocytes
• Monocytes
• Lymphocytes
NK, T, B (more soon!)
• Leukocytosis
• Increase in WBCs
• Leukopenia
• Decrease in WBCs
• Neutrophilia
• Increase in circulating neutrophils
• Neutropenia
• Decrease in circulating neutrophils
• Shift to the left
• Immature bands are increased during infection. Bands are immature white cells
that haven’t had the chance to grow to what they need to be. Typically implies
you have an infection
Acute inflammation
• Vascular Stage:
• Vasodilation increased blood flow to area
• Increased vascular permeability
• Cells involved can exit vasculature and get to area!
• Redness, Swelling, Pain, Impaired Function, Heat
Result of SIRS
• No intravascular volume because it all leaks into the tissues
• Low to NO blood pressure
• NO clotting mechanism (DIC=disseminated intravascular coagulation)
• Oxygen supply and demand IMBALANCED
• A lot of trauma = high risk for SIRS
• Tissue & organs die
• MODS (multiorgan dysfunction syndrome)=DEATH
Septic Shock (reaction to the pathogen that is invading)
 Microorganisms invade the body and initiate a Systemic Inflammatory Response (SIR)
 Perfusion abnormalities with organ dysfunction
 Sepsis=
 Gram (+) Gram (–) aerobes, anaerobes, fungi, viruses