Week 3 Lecture: Fluid Balance and Inflammation Flashcards
Total Body Water (TBW):
sum of all fluids within body compartments
How much is TBW in adults?
Is about 60% of body weight in adults
How is TBW usually expressed?
Volume of TBW is usually expressed as a percentage of body weight in kilograms
One liter of water weighs 2.2lb (1kg)
Intracellular fluid (ICF)
is all the fluid within cells and comprises about two-thirds of TBW.
How much TBW does intracellular fluid fluid comprise of?
comprises about two-thirds of TBW.
Extracellular fluid (ECF)
Extracellular fluid (ECF) is all the fluid outside the cells and comprises about one-third of TBW. ECF includes the interstitial fluid, the intravascular fluid, and the various transcellular fluids
How much tbw does ecf comprise of?
comprises about one-third of TBW.
What does ECF include?
ECF includes the interstitial fluid, the intravascular fluid, and the various transcellular fluids
interstitial fluid
The interstitial fluid is the fluid found in the spaces between cells but not within the blood vessels.
Intravascular Fluid
is the fluid found within blood vessels
What is Intravascular Fluid commonly known as:
it is more commonly known as the blood plasma
Transcellular fluids
the smallest component of extracellular fluids, are the fluids contained within epithelial-lined cavities of the body.
Examples of transcellular fluid
Examples of transcellular fluid include synovial fluid, cerebral spinal fluid, gastrointestinal fluids, pleural fluids, pericardial fluids, peritoneal fluids, and urine.
Filtration
Refers to fluid movement out of the capillary and into the interstitial space
Reabsorption
Reabsorption refers to fluid movement into the capillary from the interstitial space.
Capillary hydrostatic pressure (blood pressure)
facilitates the movement of water from the capillary into the interstitial space.
Capillary (plasma) oncotic pressure
osmotically attracts water from the interstitial space into the capillary.
Interstitial hydrostatic pressure
facilitates the inward movement of water from the interstitial space into the capillary.
Interstitial oncotic pressure
osmotically attracts water from the capillary into the interstitial space.
What occurs at arterial end of the capillary?
hydrostatic pressure exceeds capillary oncotic pressure; thus fluid moves into the interstitial space (filtration).
What happens at the venous end of the capillary?
At the venous end of the capillary, oncotic pressure within the capillary exceeds capillary hydrostatic pressure; thus fluids move into the capillary to enter into the circulation (reabsorption).
Edema
Edema is the excessive accumulation of fluid within the interstitial spaces.
How does edema result?
It results from a shift of fluid from the capillaries (intravascular fluid) or lymphatic vessels into the tissues
Physiologic conditions that promote fluid flow into the tissues that lead to edema include
(1) increased capillary hydrostatic pressure,
(2) decreased plasma oncotic pressure,
(3) increased capillary membrane permeability, and
(4) lymphatic channel obstruction.
The sodium concentration is regulated by
The sodium concentration is regulated by the renal effects of aldosterone
Water balance is regulated primarily by
Water balance is regulated primarily by antidiuretic hormone (ADH) , also known as vasopressin
Primary ECF cation
Sodium (Na+) accounts for 90% of the ECF cations (positively charged ions)
Primary ECF cation
chloride and bicarbonate, the two major anions (negatively charged ions),
Aldosterone
Hormonal regulation of sodium (and potassium) balance is mediated by aldosterone, a mineralocorticoid synthesized and secreted from the adrenal cortex.
Water balance is regulated by
Water balance is regulated by the secretion of ADH, also known as vasopressin .
When is ADH produced?
ADH is secreted when plasma osmolality increases or circulating blood volume decreases, causing a drop in blood pressure
When does increased plasma osmolality occur?
Increased Plasma osmolality occurs when there is a decrease in water or an excess concentration of sodium in relation to total body water.
Stimulation of osmoreceptors results in
The increased osmolality stimulates hypothalamic osmoreceptors , resulting in thirst.
Three things that stimulate thirst and the release of pituitary ADH, which prompt fluid consumption
- Osmoreceptors
- Volume Sensitive Receptors
- Baroreceptors
When do sodium imbalances occur?
Sodium imbalances occur with gains or losses of body water.
When do water imbalances occur?
Water imbalances develop with gains or losses of salt.
Tonicity
the change in the concentration of solutes in relation to the amount of water present
What causes hypovolemia?
Isotonic fluid loss causes hypovolemia
What causes hypervolemia?
Isotonic fluid excess causes hypervolemia.
What are the three defenses involved in immunity?
First line: Innate Immunity
Second line: Inflammation/rapid nonspecific response
Third: Adaptive (acquired) (specific) immunity/ Antibodies-immunoglobins
First line of defense in immunity:
Innate immunity
Innate immunity
includes natural barriers and inflammation
Innate barriers form the first line of defense at the body’s surfaces. They serve to prevent damage by the environment and thwart infection by pathogenic microorganisms.
Second line of immune defense
inflammatory response
Inflammation response characteristics
rapid
nonspecific response
same generic response no matter what issue is
Inflammatory response
the inflammatory response, is activated to protect the body from further injury, fight infection, and promote healing.
Third line of defense
adaptive immunity (also known as acquired or specific immunity)
Another word for an immunoglobin
Ig
An immunoglobin is an antibody
Adaptive immunity (also known as acquired or specific immunity)
is induced through a slower and more specific process and targets particular invaders and diseased tissues for the purpose of eradicating them.
Five pillars of local inflammation
- Rubor (redness, erythema)
- Calor (heat)
- Tumor (swelling)
- Dolor (pain)
- Functio laesa (loss of function)
Why does heat/redness occur as a response to inflammation?
Heat occurs because increased blood flow to the site. Vasodilation occurs
Arterial blood is warm
Why does swelling/loss of function occur in inflammation?
leaky capillaries- capillaries are more permeable to substances
swelling causes lack of function
Ultimate result of inflammation:
The ultimate result of these changes is the migration of leukocytes, plasma proteins, and other biochemical mediators from the circulation into the nearby damaged tissue, where they can work together to destroy invaders, limit tissue injury, and promote healing. `
Three key plasma protein systems that are essential to an effective inflammatory response
- Complement system
- Clotting system
- Kinin system
The complement system
intensifies or complements the capacity of antibodies and phagocytes to clear pathogens and damaged cells and activate inflammation.
proteins normally in blood further triggers inflammation
Coagulation system
is a group of plasma proteins, which, when activated sequentially, form a blood clot
Kinin System
series of proteins
end result is primarily reana kinin, which is associated with pain
Systemic Manifestations of Acute Inflammation
- fever
- leukocytosis
- increased levels of circulating plasma proteins
What are mediators in inflammation do?
Mediators are substances released from cells that stimulate a response
Other ways to measure inflammation in the blood
- C-reactive protein
- ESR: how long for rbc to settle at bottom of test tube
How is adaptive immunity characterized?
specific and involves antibodies
Passive immunity
You have immunity but you didn’t make the antibodies
Example of passive imunity
breastmilk
Active immunity
Develops after exposure to the antigen
Antigen is then able to stimulate an immune response
Antigen
Substance is able to stimulate an immune system
Example of artificial active immunity
Vaccine
Example of natural active immunity
disease
Five antibodies circulating in blood classes
IgG
IgA
IgM
IgE
IgD
So when we have an immune problem, if I have a problem with my immune response. Or if I have a disease of my immune system , Why might that be?
- it’s either going to be that my immune system is working too much.
- not working enough
3.
Hypersensitivity
Your response is dramatic
Different types of immune sensitivity
Type I- IgE mediated
Type 2- Tissue-related reactions
Type 3-Immune-complex mediated
Type 4- Cell mediated-delayed
Type I-IgE mediated
allergic response (hives to analphylaxis)
Type 2: Tissue Specific reactions
body overreacting to specific tissue
ex; thyroid disease
Allo-immunity
Blood transfusion reaction
What type of hypersensitivity are blood transfusions?
Type 2 sensitivities
Type 3: Immune complex-mediated
are not organ specific
ex; rhemetoid arthritis (abnormal antibody attacks another antibody)
Type 4: Cell-mediated delayed
symptoms occur 48 hours after exposure
no antibody involved
T cells are involved
Which hypersensitivity type does not have antibody involved at all and is not humoral mediated
Type 4: T cells are involved
not humoral or antibody mediated
Two types of immune deficiencies:
- Primary (congenital) immunodeficiencies
- Secondary (acquired) immunodeficiency
- Primary (congenital) immunodeficiencies
Genetic anomaly
- Secondary (acquired) immunodeficiency
Caused by another illness
more common
malignancy, immunosuppressive, AIDS
As a general rule, what do we think of immunosuppressants?
As a general rule, immunosuppressants are good, and are frequently used to do things like prevent organ rejection and are very important for treatment of autoimmune diseases
Immunosuppressants
Inhibit immune response
Uses of Immunosuppressants
- Prevention of organ rejection
- Treatment of autoimmune diseases
Toxicity caused by immunosuppressants:
- increased risk of infection
- increased risk of neoplasms (cancers)- our cells scavenge around for abnormal cells
Calcineurin Inhibitors- principle use
Prevention of organ rejection in transplant recipients
What does inhibition of calcineurin cause?
Inhibition of calcineurin suppresse production of interleukin (IL-2)
What is interleukin (IL-2) needed for?
IL-2 is needed for T-cell proliferation
Example of calcineurin inhibitors that are the most effective immunosuppressants available
Cyclosporine
tacrolimus
pimecrolimus
What is the drug of choice for organ rejection?
Cyclosporine
Adverse effects of Calcineurin Inhibitors
Nephrotoxicity
Infection
Hepatotoxicity
Lymphoma
Hypertension
Of all adverse effects of calcineurin inhibitors, what is common but manageable?
Hypertension
Food and Drug Interactions having to do with calcineurin inhibitors
Grapefruit juice- p450 inhibitor that leads to cyclosporin toxicity that can lead to nephrotoxicity/hepatotocity
Nephrotoxic meds- other nephrotoxic drugs +nephrotoxic drugs = bad; be concerned if pt is on another nephrotoxic drug
What are glucocorticoids used for
- Used to widely suppress immune response
- Large doses used to prevent rejection
Glucocorticoids are used to suppress immune response, what are some examples:
Suppression of allograft rejection
treatment of asthma
rhemetoid arthritis
systemic lupus erythematosus (SLE)
MS
What are the adverse effects of glucocorticoids associated with in regards to usage?
More adverse effects are associated with long term use or high dosage cortical steriods
Ways that glucocorticoids can be administered?
- systemic administration- more likely to have adverse effects
- local administration
Which type of glucocortisoids have an effect on sodium, water and aldosterone?
The shorter acting glucocortisoids have greatest effect on the aldosterone and sodium and water retention
Short term adverse effects of glucocorticoids?
Mental agitation
lack of sleep (insomnia)
Large doses of glucocortisoids used to prevent rejection cause what:
Increased risk of infection
thinning of skin
bone dissolution with fracture
impaired growth in children
suppression of hypothalmic-pituitary adrenal axis
Adverse effects of long term use:
osteoporosis
fat redistribution/muscle loss
hyperglycemia
How do you stop cortisol and why do it this way?
You taper off the med
This is because your own adrenal glands shut down their cortisol factories. The brain senses plenty of cortisol, so adrenal gland has no signal to make more
What happens if you abruptly stop cortisol?
Your adrenal glands cannot produce enough fast enough to replace what you were taking.
You need to slowly wean to allow adrenal glands to make more
Why do we care that body can make enough cortisol?
Because our body won’t respond well to stress
hypoglycemia
low bp from low cortisol
Cytotoxic Drugs
Suppress immune response by killing B and T lymphocytes undergoing proliferation
Negative effect of cytotoxic drugs
they are nonspecific; toxic to all proliferating cells (rbcs and platelets too)
Adverse effects of cytotoxic drugs
Bone marrow suppression
GI disturbances
Reduced fertility
alopecia
Bone marrow suppression caused by cytotoxic drugs lead to:
- Neutropenia
- Thrombocytopenia
How should you handle cytotoxic drugs? why?
Use PPE
You are at risk when you are exposed to it, even by touching
