Pathologic Processes: Implications for Nursing (ONLINE COURSE)
REQUIRED READING DOCUMENT #2
Includes Alterations in Fluids & Solutes, Altered Cellular and Tissue Biology;
Altered Cellular Proliferation
Instructions:
1. Read this entire RRD (Required Reading Document) and other documents mentioned.
2. Work on Assignment #2 and submit by designated deadline.
Note about objectives /outcomes and studying for this course:
For ALL content in this course, the student will be able to DESCRIBE/DISCUSS/IDENTIFY correlations (links) between pathophysiology of the disease and its clinical manifestations. In other words, #1: how does the pathophysiology of a particular disease cause the signs and symptoms, and #2: if a patient presents the signs and symptoms of a disease, be able to use critical thinking to figure out the disease process that is most likely in that context.
Alterations in Fluids and Solutes
Objectives /outcomes
DESCRIBE/DISCUSS/IDENTIFY:
- The concepts of physiologic and pathophysiologic fluid shifts between the body’s fluid compartments as driven by alterations in osmolality, oncotic pressure, tonicity, hydrostatic pressure, and control mechanisms such as RAAS, natriuretic peptide system, & ADH.
- The effect of alterations of key molecular substances such as hydrogen, sodium, potassium, chloride, calcium, phosphorus, magnesium, proteins, O2, CO2, HCO3 and glucose on fluid shifts and other body processes, including acid / base balance.
- Normal cellular metabolism and its alternate states, including anaerobic metabolism and the processes of glycogenesis, glycogenolysis, and gluconeogenesis.
- The relationship of all the above to certain disease processes and signs and symptoms (S&S), including:
- fluid overload and fluid deficit states, including SIADH & DI.
- basic states of acidosis and alkalosis.
- hyperpolarized and hypopolarized plasma membrane.
- alterations of glucose availability.
- alterations in usage of certain vitamins.
Outline for Alterations in Fluids & Electrolytes
Fluid shift pathologies
A. Overview of fluid-related problems
B. Increased blood osmolality (water loss)
C. Decreased blood osmolality (water gain; protein loss).
| Review separate document “Fluid Shift Concept Map” for reinforcement of the info in these notes. . |
A. Overview of fluid-related problems (usually when general term “fluids” is used, it is referring to general water status and/or shifts in distribution of water in body; also called “volume-related” problems)
1. normal daily fluid processing:
| NOTE: interstitium + cells = tissue. Remember that when talking about diffusion of solutes or osmosis of fluids I will just say “blood to tissue” or “tissue to blood.” |
a. the body receives about 2100 ml of fluid intake normally per day, usually orally (in food, in water or other liquid that is drunk) and it quickly enters the plasma compartment from the capillaries of the gut.
b. once in the plasma compartment, water is circulated to the tissues and various fluid shifts take place–water shifts from the blood into the tissue, or from the tissue into the blood, depending on various needs, and always with the goal of maintaining homeostasis between fluid compartments (ie, fluid concentration in all the compartments are ultimately kept essentially the same or near-same); eventually some of the fluid is excreted as part of products such as urine, feces, sweat, exhaled air.
c. this movement of water (ie, fluid shifts) between compartments (plasma vs interstitial vs cell) is called osmosis and it is “ruled” by osmolality
2. osmosis
a. fluids shift from one compartment to another via the process of osmosis
b. review of osmosis:
| *** “Concentration” of any solution correlates with the percent, or ration, of solute particles in that solution: high concentration = more solutes, less H2O; low concentration = less solutes, more H2O. *** |
1) remember that osmosis is the movement of water from one compartment to another via a semi-permeable membrane (basically this is the membrane lining the blood vessels or cells).
2) rule of osmosis: water will always want to move from a more dilute compartment to a more concentrated compartment—ie, from a compartment of less % of solutes to one with greater % of solutes (the body wants to return to having the compartments equally concentrated.)
3) think of it this way: CONCENTRATION CALLS! Osmosis is ruled by the PULLING force of higher concentration.
4) since concentration is the SAME as osmolality, then we can also say
that OSMOLALITY ORDERS!
| Be sure to keep separate & clear the difference between diffusion and osmosis: solutes will diffuse from more concentrated areas to less; osmosis is movement of water from less concentrated areas to more concentrated. |
3. osmolality & its correlates
a. osmolality is a measurement of how CONCENTRATED a compartment
is (ie, the proportion of solutes-to-water that are in that compartment’s fluid)
–concentration and osmolality are almost the same thing!
b. clinically we can measure the solute concentration of the plasma
compartment (ie, blood) by doing a serum osmolality & thus have an idea about what fluid shifts to anticipate since osmolality (concentration)
rules osmosis.
c. there are some concentration states that follow the same principles as
osmolality, and thus I call correlates (they may be used in different contexts but THEIR PROPERTIES AND PRINCIPLES ARE THE SAME AS OSMOLALITY.)
1) tonicity— interchangeable with the term “salinity” (the “saltiness” of a
| If as a nurse you were ordered to hang an IV bag of normal saline, which would you do/know? a. Hang the bag that says 1000ml 0.9% NaCl. b. Hang the bag that says 1000ml NS. c. Hang the bag that you know is isotonic to normal blood. d. Hang the bag that has a tonicity of 0.9% NaCl. e. Any of the above. Answer at the end of these notes. |
fluid, how much of it is made of salt, ie NaCl)
a) the normal tonicity (salinity) of the blood is 0.9% — that means
the saline concentration, ie amount of NaCl, in the blood is
0.9%
b) if the tonicity of the blood is higher than 0.9%, we can say the patient is hypertonic and/or hyperosmolar…either way, the blood is in some way MORE concentrated than usual.
c) if the tonicity of the blood is lower than 0.9%, we can say the patient is hypotonic and/or hypoosmolar…either way, the blood is in some way LESS concentrated than usual.
d) an adjective that we use for normal tonicity is “isotonic;” ie,
we can say that any fluid which has a saline concentration (tonicity) of 0.9% is isotonic to normal blood.
(1) a nickname for any saline fluid that is isotonic to the blood is “normal saline” AKA just “NS”.
(2) a bag of hypotonic IV fluid has a lower tonicity than normal blood; ex—a bag of 0.45% NaCl (AKA 0.45%NS)
| Concentration calls! (Higher concentration pulls in water). Osmolality orders! (Higher osmolality pulls in water.) |
(3) a bag of hypertonic IV fluid has a higher tonicity than normal blood; ex—a bag of 3% NaCl (AKA 3%NS).
2) osmotic pressure – the pressure exerted by all the solutes in a compartment; it correlates with osmolality —ie, the higher the osmolality, the higher the osmotic pressure.
3) oncotic pressure (AKA colloidal osmotic pressure)—exactly the same principle as osmotic pressure, but refers specifically to protein molecules.
4. changes in fluid compartments
a. a change in the concentration of one fluid compartment often means there will be a fluid shift—ie, water will SHIFT INTO OR OUT OF that compartment based on the principle of osmosis
| Remember when we talk about the principles of concentration, we know we can basically substitute that word with osmolality and osmotic pressure; and if the concentration we are discussing has to do with salinity, we can use “tonicity;” if it has to do with protein in the blood we can use “oncotic pressure.” |
b. when given a scenario in which you have to figure out which way fluid will shift (blood to tissue [B to T] or tissue to blood [T to B]?), always think of the concentration change as occurring FIRST in the blood, THEN in the tissue; also think in very orderly steps, like this:
1) “In this scenario, did the blood become MORE concentrated or LESS?”
2) “When the blood (with its concentration change) circulates to the tissue (which initially has NORMAL concentration), which way will water move, from B to T or T to B?”
c. in general, we will focus on two fluid balance changes:
1) water is pathologically LOST by the body, so that there is increased concentration (osmolality) of the plasma space (blood); ultimately this causes a tissue-to-blood (T to B) fluid shift.
2) water is pathologically gained by the body or protein is lost, so that the concentration of the plasma space (blood) is decreased; ultimately this causes a blood-to-tissue (B to T) fluid shift.
B. Increased blood osmolality (pathologic water LOSS).
1. the most common mechanism for an increase in blood osmolality is loss of water a. there are many permutations of fluid loss & subsequent shifts; we will be
discussing only pure water loss.
b. pathologic water loss can occur via:
1) inadequate intake (ex—patient too sick to drink fluids).
2) increased output; ex:
a) vomiting.
b) diarrhea
c) increased urination (as occurs in diabetes insipidus, diabetes
mellitus, & Addison’s—these all to be discussed in later lectures)
c. simple diagram: disease causing a continuing water loss from bodyà water
loss from bloodàincreased blood osmolalityàwater loss from cellsà overall
dehydration.
2. step-by-step example of fluid shifts when there is water loss, such as in severe diarrhea caused by intestinal infection:
a. in certain intestinal infections, a microbe causes disruption in the integrity of the walls of millions of capillaries that line the intestines à water “leaks” from the capillaries into the lumen of the intestines (the increase in fecal liquid is part of what causes the diarrhea).
b. as water leaks from the local capillaries, eventually the blood of the entire circulatory system is becoming more concentrated than the surrounding tissues all over the body (thus, as per the rule, the vascular compartment is the first to change its composition)
c. next, there is a domino effect of fluid shifting: since the plasma compartment (ie, the bloodstream all over the body) now has a higher osmolality than the next door tissue compartment (all over the body), water will be PULLED INTO the plasma compartment, leaving the tissue cells dehydrated & shrunken. (ie, ultimate shift of fluid is T to B)
| Breaking it down further, it actually happens like this: the blood now having a higher osmolality than the next door interstitial compartment, water will be PULLED INTO the plasma compartment & the interstitial compartment will now have a higher osmolality than the next door intracellular compartment; water will then be PULLED INTO the interstitial compartment, leaving the cells dehydrated & shrunken. |
3. S&S caused by T-to-B fluid shift such as example above
a. think “dehydration;” in nursespeak, we would think of this state as a “fluid volume deficit.”
| Skin turgor – state of flexibility or tightness of the skin cells due to how much water they have. A certain amount of water in these cells is desired for good elasticity & protection. If the skin is pulled up & snaps back, it has good recoil and elasticity, indicating adequate hydration of the skin cells—this is called “good skin turgor,” or “good recoil.” If there is too much water in the tissue (edema), the skin will be tight. If there is not enough, the skin will be loose and have little recoil; when pulled, it “tents” up. This is called “poor skin turgor” or “tenting” and indicates dehydration. |
b. as tissue cells have their water “pulled out” into the vascular system, which is now more concentrated than the tissues (CONCENTRATION CALLS), the tissues eventually show dehydration all over the body in the following ways:
1) dry mucus membranes
2) poor skin turgor — skin loose, “tents” when pinched, won’t “snap back.” See: http://www.youtube.com/watch?v=VbTXfWgi4YQ & http://www.youtube.com/watch?v=UFTC8TDjeOY&NR=1
3) sunken eyes
4) sunken fontanels in babies
5) diminished urinary output (oliguria) & also urine concentration increases.
6) sometimes low BP (blood pressure) if dehydration bad enough
7) acute CNS (central nervous system) changes related to dehydrated brain cells– restlessness, confusion, unconsciousness, convulsions.
c. if we did lab work, we would see a high serum osmolality (we would consider this patient’s blood to be hyperosmolar.
4. the body has certain intrinsic hormonal compensatory mechanisms to correct fluid volume deficit (and/or low blood pressure).
a. RAAS—Renin-Angiotensin-Aldosterone System
1) increased renin is secreted by the kidneys in the following situations: a) when blood osmolality is high (usually because of water loss)
and/or
b) when fluid volume in the circulation is low due to blood loss
and /or
c) BP is low
2) renin stimulates secretion of angiotensin I à becomes angiotensin II with the “help” of ACE (angiotensin converting enzyme)
3) angiotensin II has two important duties: stimulates peripheral vasoconstriction & increases secretion of aldosterone from the adrenal gland
a) peripheral vasoconstriction means less blood will flow into the constricted blood vessels in the periphery & will stay in the central circulation.
b) aldosterone causes kidney tubules to “hold on” to Na+à water follows Na+ back into circulation instead of going out with urine àurine output decreasesàwater in blood and general circulatory volume increases
4) summary: RAAS causes increased circulatory fluid volume and compensates for (ie, “fixes”) the initial problem of low fluid volume (as
in water loss), low total blood volume (as in bleeding), &/ or low BP.
5) when fluid volume is high, the RAAS is suppressed.
b. ADH— antidiuretic hormone secretion assists RAAS.
| CTQ (critical thinking question): A person’s body, left alone, will institute the RAAS to help with dehydration, as just seen. But if we were to step in with a medical intervention for someone with water loss and HIGH osmolality, which IV bag would you choose as best to begin the patient’s return to osmolar homeostasis? ( IV fluid goes directly into the plasma space, thus changing the concentration of that space.) a. 3% NS b. a hypertonic bag c. a gin and tonic bag d. 0.45% NS Answer at the end of these notes. |
C. Decreased blood osmolality (pathologic water GAIN or protein LOSS).
1. the most common mechanisms for a decrease in blood osmolality are pathologic amount of excess water and/or loss of solutes (in particular we will look at protein loss)
2. excess water
a. general mechanisms & sequelae
1) pathologic increase of water in the circulation can occur from several etiologies (see following sections), with the result being a dilution of the blood and a lower serum osmolality than its next-door neighbor, the tissue (as per the “rule,” the vascular compartment is the first to change its composition)
2) since the blood has changed to a lower osmolality than the nextdoor tissue compartment, which way will water will be PULLED (“called”)?
INTO the tissue or INTO the blood? (ie, T to B or B to T?)
3) as excess fluid is pulled into the tissue, the resultant pathologic accumulation is called edema, which can impair body processes such as healing and oxygen exchange because of increased distance for nutrients and waste products to move between capillaries and cells
4) simple diagrams (mini-concept maps):
a) disease causing an overall water gain to bodyà water gain to bloodàdecreased osmolalityàwater gain to tissue (edema)à overall fluid overload.
b) disease causing loss of protein from bodyàdecreased oncotic
pressure (and osmolality) of bloodàwater gain to tissue (edema).
b. situations that can cause excess water in the blood & eventually in the tissues (water shifts from B to T):
1) excess intake of fluid
a) psychotic water drinking (“water intoxication”)
b) too much IV fluid
| IMPORTANT NOTE: In this section we have talked about edema resulting from osmotic changes in the blood that then cause fluid shift to the tissue. But edema can also be caused by simple mechanical means such as increased hydrostatic pressure in the blood. Remember from A&P that hydrostatic pressure is a “pushing” pressure—pushes fluid OUT of a compartment into the next. Example of this would be someone with high blood pressureà can sometimes “push” fluid from blood to tissue. |
and/or
2) low output— inability to process and/or get rid of appropriate amount of water, such as in kidney failure, so water accumulates pathologically in the body.
and/or
3) hormonal problems such as SIADH– syndrome of inappropriate antidiuretic hormone (think of the “I” in SIADH as “increased” ADH).
a) possible etiologies of SIADH
(1) ectopically-produced (ectopic = “outside usual”) ADH such as from small-cell bronchogenic cancer
(2) various drugs, especially general anesthetics (SIADH sometimes seen in post-op recovery period).
(3) trauma to brain such as brain tumors, head injury, etc. (swelling of brain puts pressure on pituitary gland)
b) mechanism of action & S&S
(1) characterized by abnormally high levels of ADH: you “hold onto” water too much by abnormally decreasing urination àresults in increased vascular fluid volume (essentially means that water has been added to the blood = diluted plasma compartment).
(2) S&S include decreased urine output (oliguria) because your body is holding onto water inappropriately, & other
fluid volume excess S&S (see below)
3. solute loss (especially proteins)
a. the solutes that most affect fluid shifts by their loss are
1) Na+, which can be lost via excess sweating or certain disease processes, and/or
2) proteins (protein loss in the blood – hypoproteinemia)
b. some causes of hypoproteinemia
1) diminished protein production such as certain types of liver diseases like cirrhosis (the liver produces many proteins such as albumin, so if liver is diseased, can’t produce proteins) and
2) diminished protein intake, which cause certain protein malnutrition states such as kwashiorkor.
3) plasma protein loss via certain kidney diseases such as glomerulonephritis:
a) in certain diseases, the glomeruli of the kidneys lose the ability to appropriately keep protein molecules in the blood where they belong, and large numbers of proteins “spill out” into the urine (proteinuria)
b) the sequelae of this disease process include fluid shifts that develop like this:
(1) there are now less proteins in the blood (hypoproteinemia),
(2) this means less solutes in the blood than normal, so the plasma compartment has a lower concentration than normal, as well as a lower concentration than its next door neighbor, the tissue.
| Protein molecule concentration in blood |
| Protein molecule concentration in tissue |
(3) thus what we have so far is a vascular space which is now hypoosmolar & has a low oncotic pressure next to tissue that has normal osmolality
(4) following the rules of osmosis (CONCENTRATION CALLS), water will be pulled which way? T to B or B to T? (draw arrow showing which way WATER goes)
(5) will this patient (IE, a patient with hypoproteinemia) look dehydrated or edematous?
| B |
| T |
(6) another sequela of all this is that the patient is at risk for major nutritional problems because of not have enough proteins to create muscle mass & maintain protein- based processes, etc.
4. S&S caused by B-to-T fluid shifts
a. in “nurseland”, we generally think of a person with B-to-T fluid shifts as being in a state of “fluid volume overload or excess.”
b. as tissues “pull in” water from the diluted vascular system, they eventually show their water overload as edema that can occur anywhere in body; examples:
1) under skin: skin of the feet and/or hands will appear tight & puffy and is called peripheral edema. Push a finger into the swollen skin – if an indentation is noted then we would call it “pitting edema.”
2) in lung tissue—pulmonary edema (“wet lungs”): manifested as cough and/or SOB &/or crackles while listening with stethoscope.
3) acute CNS (central nervous system) changes related to swelling of brain cells — restlessness, confusion, unconsciousness, convulsions.
c. if we did lab work, we would see a low serum osmolality (we would consider this patient’s blood to be hypoosmolar, hypotonic, have low oncotic pressure, and low osmotic pressure—all similar terms– compared to normal blood)
5. compensatory mechanisms to correct fluid overload: natriuretic peptide system (NPS)
a. when fluid volume is high, the right atrium and left ventricle detect that too much fluid is reaching them.
b. they secrete ANP (atrial natriuretic peptide) & BNP (b-type natriuretic peptide à these peptides reach the kidneys via the circulation & stimulate them to increase urination (diuresis)à fluid volume goes down.
c. when fluid volume is low, this system is suppressed.
| Summary note/ clarification: When you are given test questions having to do with potassium (hypo- or hyperkalemia) or calcium (hypo- or hypercalcemia), think “electrical issues,” such as hyper vs hypo polarization. When you are given test questions having to do with sodium, water, protein, and/or osmolality issues, think “fluid shifts” such as edema & fluid deficit problems. |
***********************************************
| Test yourself: Which mechanism causes the body to diurese when vascular volume increases excessively– the natriuretic peptides system or the RAAS & ADH ? | Test yourself: Which mechanism causes the body to “hang on” to water when vascular volume decreases excessively– the natriuretic peptides system or the RAAS & ADH ? |
FYI (not on test except for what was covered in the fluid shift parts of these notes)—
IV fluids & their tonicity
| 0.9% NaCl –normal saline (NS) | isotonic |
| 0.45% NaCl — AKA ½ NS | hypotonic |
| Lactated Ringer’s solution (LR) | isotonic |
| D5W — 5% dextrose in water (acts as a hypotonic solution in body because the dextrose is quickly ushered out of blood and absorbed) | isotonic in the bag |
| D5 NaCl – AKA D5NS | hypertonic |
| D5 in Lactated Ringer’s (D5LR) | hypertonic |
| D5 0.45% NaCl – AKA D5 ½ NS (the dextrose is quickly ushered out of blood and absorbed, so the fluid then acts as a hypotonic agent) | hypertonic in the bag |
| 3% NaCl | hypertonic |
| Page 5 CTQ: A person’s body, left alone, will institute the RAAS to help with dehydration, as just seen. But if we were to step in with a medical intervention for someone with water loss and HIGH osmolality, which IV bag would you choose as best to begin the patient’s return to osmolar homeostasis? ( IV fluid goes directly into the plasma space, thus changing the concentration of that space.) a. 3% NS b. a hypertonic bag c. a gin and tonic bag d. 0.45% NS (this is a hypotonic solution… when it enters the blood, it will begin changing the blood to lower concentration than tissues, so that water will be PULLED into the tissues, which is what this person needed) |
| Page 2 question & answers: If as a nurse you were ordered to hang an IV bag of normal saline, which would you do/know? a. Hang the bag that says 1000ml 0.9% NaCl. b. Hang the bag that says 1000ml NS. c. Hang the bag that you know is isotonic to normal blood. d. Hang the bag that has a tonicity of 0.9% NaCl. e. Any of the above ANSWER: E – they are all ways to think of NS. |
| Protein molecule concentration in blood |
Answers from page 7:
| Protein molecule concentration in tissue |
(4) following the rules of osmosis (CONCENTRATION CALLS), water will be pulled which way? T to B or B to T? (draw arrow showing which way WATER goes)
(5) will this patient (IE, a patient with hypoproteinemia) look dehydrated or edematous?
| Arrow shows fluid being pulled into tissues, causing edema. |
| B | T |
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Nursing 3366 Pathologic Processes: Implications for Nursing
Lecture Notes: Altered Tissue and Cellular Proliferation
Objectives /outcomes for this subject:
DESCRIBE/DISCUSS/IDENTIFY:
- Key aspects of normal tissue types and normal cellular life /death cycle such as differentiation & apoptosis.
- Aspects of the cell injury process such as spectrum of injury, cell swelling, enzymatic spillage such as CK, myoglobin, and troponin.
- Causative factors and sequela of reversible and irreversible cellular injury such as hypoxia, ischemia, necrosis, infarction, carbon monoxide poisoning, free radicals, cellular accumulation and anemia.
- Factors that contribute to the development and destructive properties of free radicals, effect on body cell, and counteractive therapeutic measures.
- Causative factors, mechanism and significance of tissue adaptation processes such as atrophy, hypertrophy, hyperplasia, metaplasia and dysplasia.
- Causative factors in pathologic cellular proliferation, including genetic influence, infective processes and environmental effects.
- Nomenclature of benign versus malignant cancers, diagnostic & genetic markers, classifications, staging, and clinical significance of each.
8. Correlation of information in 1-5 with disease processes and manifestations.
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Outline
I. Cellular Growth, Death and Injury
A. Overview
B. More on cellular injury
II. Examples of types/causes of cellular injury
A. Ischemia
B. Carbon monoxide (CO) poisoning
C. Abnormal cellular accumulations
D. Free radicals
E. Abnormal cellular proliferation
III. Cellular proliferation and alterations
A. Overview
B. Cancer
IV. Cellular Adaptation
A. Overview of adaptation
B. Forms of adaptation
V. Immobility
A. Concept definition
B. Potential Complications
C. Treatment/Nursing interventions
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I. Cellular Growth, Death and Injury
A. Overview.
| More on erythropoietin: made by the kidneys, it is important in stimulating growth and development of RBCs. No erythropoietin = less RBCs = anemia. Anemia is a state of low numbers of RBCs & results S&S of ______________________ _____________________ |
1. birth & growth of cells: most cells have very well-defined growth and development of structure & function
a. as programmed by their genetic makeup, cells have different degrees of differentiation (synonyms: “organization”
and/or “specialization”).
b. there is a spectrum from fairly rudimentary all the way to highly differentiated cells, such as nerve cells and cardiac cells.
c. this development is helped along by many hormones such as erythropoetin and other growth mediators.
2. death of cells
a. cell death can be the culmination of normal cycle of cell and/ or aging process, or can be as a result of a pathologic event.
b. “normal death”– apoptosis
1) apoptosis is a form of “programmed death,” or cell “suicide”
2) our bodies create & kill 10 billion new cells a day– if cells didn’t die, we would have gigantic and/or distorted bodies.
3) also, body has to get rid of cells that have been worn out, developed improperly, or have genetic damage
3. injury of cells
a. many events and/or triggers can cause injury to cells, upsetting homeostasis, causing some degree of cell dysfunction, and
often resulting in some sort of disease or disorder.
b. examples of types/causes of injury (more on these further on):
1) ischemia
2) carbon monoxide poisoning
3) free radicals
4) abnormal cellular accumulation such as uric acid & fat
5) abnormal cellular proliferation (cancer)
6) other: chemicals (cyanide), genetic, hypoxia, nutrition (already covered); infections, immunologic reactions (to be covered later).
c. “abnormal” cell death –necrosis occurs when a cell is injured and reaches the irreversible point on this spectrum:
B. More on cellular injury
1. overview / general process of cell injury
a. as noted above, cellular injury is a continuum in which cellular homeostasis is
affected to a varying degree, depending on many influences, including:
1) type of cell, level of differentiation, ability to adapt
2) type, severity, duration of injury
b. no matter what part of the continuum, the commonality of all injury to cells/tissue is inflammation, which is one of the first steps to healing.
c. inflammation will be covered more thoroughly later, but here we will go over very earliest steps of inflammation, which occurs at microcellular level immediately post-injury:
1) no matter what the cause of the injury, the result is almost always some level of disruption to metabolic pathway
2) sequelae of this disruption:
a) cellular swelling & leakage
b) cellular function abnormalities or complete shut-down
3) mini-concept map of above process:
d. cell swelling & leakage as “motif” in disease discussions throughout semester
1) injury/inflammation of various tissue is part of almost every disease process in some way
a) so if I mention injury and/or inflammation as part of a disease process, always think of “swelling & leakage” as part of the picture
b) ex: cellulitis: staph aureas attack on skin cellsà skin cells are injuredàinflammationà metabolic pathway of local cells disrupted à water enters cells pathologicallyà cells leak & malfunctionàS&S of painful, weeping, excoriated areas of skin.
2) if injury to muscle cells is bad enough:
a) as water is pathologically coming in, intracellular substances that are pathologically leaking out into immediate surrounding area tissue can eventually find their way into capillaries of area & thus into blood stream
| muscle cells are found ALL OVER, not just obvious places like arms & legs—heart is a muscle, parts of intestines are muscles, etc. |
b) serum lab measurements of these intracellular substances are sometimes used as diagnostic & prognostic tools—the higher the serum measurement, the worse the damage.
c) examples:
(1) creatine kinase (CK)– an enzyme found in most muscle cells (including the heart) that catalyzes transference of phosphate groups back & forth between ADP & ATP
(2) myoglobin (myo = muscle, globin= a type of protein) — found in most muscle cells.
(3) troponin –a type of protein molecule only found in heart muscle
II. Examples of types/causes of cellular injury
A. Ischemia
1. overview
a. definition: ischemia is oxygen deprivation to cells (hypoxia) due to decrease in arterial circulation to the area
b. there are many etiologies for hypoxia of tissue, but ischemia is the
most common.
c. underlying mechanism of ischemia is narrowed and/or blocked arteries
d. this narrowing or blockage can be acute or chronic
2. acute ischemia– hypoxia to tissues from sudden lack of blood supply; examples:
a. arterial embolus: clot that travels in the arteries till it suddenly gets lodged in a smaller blood vessel (arteriole or capillary)à distal tissues quickly become hypoxic.
b. sickle cell crisis: abnormally shaped RBCs get stuck in capillaries &
decreases blood supply to joints, etcàischemiaà ischemic pain.
3. chronic ischemia: better tolerated because tissues can adapt to some degree over time; examples of causes of this gradual ischemia:
a. gradual narrowing of arteries from atherosclerosis.
b. slow-developing clot (thrombus) in leg artery or coronary artery.
4. infarction
a. if ANY ischemic situation, acute or chronic, is not treated, can lead to infarction-– cell death (necrosis) that is specifically caused by lack of arterial blood supply to an area
b. examples of ischemia leading to tissue damage and/or infarct:
1) coronary artery clogged with clotà ischemia to tissues beyond (“distal to”) the clotàischemia not treatedà progresses to anoxia à infarct of distal tissue (myocardial infarction, AKA “MI”).
2) artery to foot narrowed by atherosclerosisà ischemia to distal
tissuesà infarct of distal tissues
3) unrelieved pressure on skin, such as lying immobile àprevents skin capillaries from receiving oxygenated blood (ischemia) à tissue injury & breakdown in this situation is called a pressure ulcer, stasis ulcer, “bed sore,” or decubitus (plural = decubiti).
| Clarifications (be sure you understand these terms): Hypoxia (cellular oxygen deprivation) can be caused by many things; when it is caused by an arterial circulation problem/interruption, it is called ischemia. (Remember that arteries bring O2 to tissues). So, ischemia is hypoxia SPECIFICALLY caused by an arterial circulation problem/interruption. (Picture arterial flow to the tissues being interrupted/diminished—thus the tissues become hypoxic) Hypoxia can lead to necrosis –general death of cells. Ischemia can lead to infarct –so, infarct is necrosis (death) SPECIFICALLY caused by an arterial circulation problem. |
B. Carbon monoxide (CO) poisoning
1. overview
a. CO is odorless, colorless gas produce by an incomplete combustion of fuel –in certain situations, such as malfunctioning
heaters, not enough O2 is provided to make complete combustion (conversion to CO2) .
b. people in high risk situations, such as above (using poorly functioning heaters), can inhale CO and suffer array of S&S
2. mechanism of action, S&S, treatment:
| A&P review: Each RBC has about 300 Hgb molecules, which each are capable of binding to 4 O2 molecules. The RBCs are carried to the tissues by the arteries, at which time the Hgb’s release their O2 to the cells. |
a. CO has a high affinity for hemoglobin (Hgb)– about 3000 times more so than oxygen → binds to Hgb, forming carboxyhemoglobin (HgCO)
b. HgCO prevents O2 from binding to Hgb, so tissues become hypoxicàcell damageàS&S .
c. S&S mostly relate to nervous system & depend on % of HgCO in body
–headache, giddiness, confusion, seizures, coma.
d. treatment—100% O2 by oxygen mask and/or hyperbaric chamber until HgCO levels come down to normal.
| FYI– Everyone has a certain amt of HgCO in their blood, depending on their environment– ~ 3% for non-smokers, ~7% for smokers. (This puts smokers in a higher risk category for being affected by O2-deprivation events.) S&S & treatment: mild S&S of CO poisoning begin at ~10%; hyperbaric chamber needed at ~25-30%. |
C. Abnormal cellular accumulations
| Alert: uric acid is a byproduct of the breakdown of nucleotide purines found in all cells; don’t get it mixed up with urea, a substance converted from ammonia, which is a protein breakdown byproduct. For ex, when you see the lab result “BUN”—blood urea nitrogen—this is same as a serum urea level. If gout is suspected, a serum uric acid level would be ordered. |
1. when substances accumulate in the cells pathologically they can interfere with normal cellular functions & ultimately cause cell injury; examples follow..
2. lipids; ex– fatty liver from dz processes such as alcoholism
3. urates (AKA uric acid) accumulation; ex—gout:
a. gout is systemic disease caused by buildup of uric acids in the blood-hyperuricemia
b. uric acid is breakdown product of purine, an organic compound found in all our cells; normally we excrete excess uric acid in urine.
c. people with gout are unable to process uric acid effectively, so uric acid crystals accumulate and settle in joints, causing inflammation, swelling, and pain.
d. most often settles in first metatarsal joint of the big toe or in the ankle joint.
e. tx: medications, plus a diet low in food that is high in purines, such as red meat, cream sauces, red wine.
D. Free radicals
1. what ARE free radicals?
a. free radicals can be thought of as a separate molecular “species,”
because they don’t behave like “normal” atoms & molecules.
| A free radical is a vandal! |
b. they act differently because they are a “spin-off” of abnormal, accelerated, and/or uncontrolled reactions, especially certain oxidation/ reduction (“redox”) reactions
c. typical generators of these free-radical-producing reactions are:
1) simple aging
2) environmental pollutants
3) certain drugs, & alcohol abuse
4) various types of radiation damage, including too much sun
5) certain foods such as those high in preservatives and charred meat.
d. an example of a free radical is superoxide, which at times is created in our own body during the especially rapid redox reactions of the electron transport chain.
2. how free radicals cause problems: once created in above situations, free radicals such as superoxide can destroy cells throughout the body by:
a. reacting with the lipids in cell membranes & causing lipid peroxidation
damage to the cell membraneà “leaky” cells
b. attacking proteins such as transmembrane proteins needed for ion
pumps
c. damaging DNAà altered protein synthesis & causing gene mutations
d. damaging mitochondriaà alterations in metabolism
e. damaging DNAà altered protein synthesis & cause gene mutations,
sometimes leading to cancers
3. counteracting free radicals:
a. certain vitamins like vitamins C & E can stop the wild molecular behavior of free radicals
b. also, the body can “defuse” free radicals such as superoxide by using
specialized enzymes such as superoxide dismutase
E. Abnormal cellular proliferation (cancer)… covered in next section.
| Direct causes of cellular injury (mechanical trauma)– can result in: contusions (bruises); hematomas (collection of blood in soft tissues or an enclosed space); abrasions (scrapes); lacerations (tear or rip in the skin). |
III. Cellular proliferation and alterations
A. Overview
1. cell proliferation– the multiplication or reproduction of cells, resulting in the rapid expansion of a cell population.
2. this is part of normal growth and development of cells
a. ex—our hematopoietic system (birthplace of blood cells) is chiefly located in the bone marrow
b. basic stem cell differentiates into several types of blood cells, which then mature, proliferate (multiply), & are released into the blood 3. altered cell proliferation includes disease processes such as cancer.
| FYI (not on test): Therapeutic uses for stem cells 1. because of their potential for growing into many possible different kinds of cells, human embryonic stem cells are being used to develop treatments for many different disease processes 2. basic process: egg is fertilized in vitro à over about 3-4 days grows into ball of cells (blastocyte)à placed in culture dishàover time & many other steps, stem cells develop that can grow into whatever type of tissue is needed. 3. an example of the research being done: stem cells have been cultured that are precursors to neurons that appropriately release the neurotransmitter, dopamineà these healthy neurons might possibly be implanted into brains of people with Parkinson’s disease, in which diseased neurons stop releasing dopamine. |
B. Cancer
1. definitions:
| FYI: Cancer, not heart dz, now top killer–cancer is leading disease of adults in the western world. The term cancer derives from the Greek word for “crab”—“karkinoma”—Hippocrates used it to describe the appendage-like projections extending from tumors. |
a. tumor– an abnormal mass of tissue
1) used interchangeably with neoplasm.
2) ex: malignant tumor or benign tumor; malignant neoplasm or benign neoplasm.
b. benign tumors (benign means “nice,” so medically it means NOT cancer)
1) key characteristics:
a) slower growth than malignant cells
b) area of growth well-encapsulated & non-metastasizing
c) cells in the area of growth are fairly well-differentiated & usually closely resemble the tissue they arose from.
2) ex—a lipoma is a benign neoplasm that is composed of an encapsulated area of fat cells that have undergone overgrowth.
c. malignant tumor or “malignancy;” interchangeable with “cancer”
1) key characteristics—very rapid growth rate of cells that are poorly differentiated
2) location
a) can occur in a specific site; ex– local malignant tumor such as cancerous skin lesion
b) and/or metastasis can occur (verb: metastasize)
(1) refers to propensity of malignant cells to invade sites distant to immediate area
(2) metastasis is major cause of illness and death resulting from most human malignant dz
c) some cancers by nature are wide-spread, such as leukemia
3) note: the study or field of cancer is referred to as oncology
2. etiologies of cancer – basic etiology is gene mutations (“gene hits”) prompted by a variety of factors, including:
a. “normal” aging/ wear & tear of cells à older age increases number of “hits” to DNA
b. heredity; ex– certain kinds of breast cancer run in families
c. environmental, from free radicals and carcinogens inherent in:
1) use of tobacco, alcohol, certain drugs
2) ingestion of certain dietary substances such as nitrates used in preservatives
3) air pollution; ultraviolet light (sunlight); ionizing radiation
4) occupational hazards such as asbestos
e. invading organisms; ex—viruses such as:
1) some species of HPV (human papillomavirus), which are contracted sexually, can cause cervical cancer in woman.
HPV has also been linked as a cause of mouth and throat cancer.
2) HBV & HCV which cause hepatitis B & C & increase risk of liver cancer
3. mechanism of action in cancer genesis
a. no matter what the initiating factor that causes the accumulation of genetic “hits,” or mutations, when sufficient mutations have occurred, cancer can develop
b. the genetic mutation that sets cancer into motion is often called an oncogene.
c. the oncogene promotes clonal proliferation—a rapid increase in growth & development—by:
1) stimulating cells to “overreact” to growth factor signals—causes wild, rapid duplication but very little differentiation.
| Remember, the more differentiated a cell is, the more organized & specialized it is. Ex–nerve cells are highly differentiated, whereas cancer cells are “wild” and poorly differentiated. Synonym for “poor differentiation” or “loss of differentiation”—anaplasia. |
a) instead of differentiating into a specific tissue type with a specific function, as normal cells do, cancer cells do not differentiate; they stay in a younger stage of development and continue to replicate.
b) this loss of differentiation is called anaplasia.
2) overriding normal “braking” signals
3) stimulating the development of tumor cell’s very own blood supply—angiogenesis (development
of new blood vessels); this is partly why cancer kills—cancer cells divert nourishment from our other cells
4. diagnosis:
a. diagnostic tests for cancers are many—CAT scans (computed axial tomography), MRIs (magnetic resonance imaging), biopsies (obtaining tissue for microscopic examination), etc; also can look for tumor and genetic markers.
b. tumor markers—substances in the body produced by cancer cells or released by cancer-damaged tissue that can be found in blood, spinal fluid, or urine
1) may be a hormone, enzyme, antigen, antibody, gene
2) example of blood test– PSA—prostate specific antigen
a) glycoprotein found in prostate gland cells that are released into the blood when cancer invades the prostate
b) can help to detect prostate cancer very early
c. genetic markers— genetic abnormalities that are found in some people that predict odds of having certain types of cancers; example:
| Term clarification: Leukocytosis: a generic term meaning the condition of too many WBCs in the blood; can develop in many disease processes. Leukemia is a diagnosis, actually a disease in itself; one sign of leukemia is leukocytosis. |
1) chronic myeloid (AKA myelocytic or myelogenous) leukemia (CML) develops because of a translocation (exchange) of pieces of chromosome; in this case, one chromosome gets shortened (sort of “squashed”) in this process—this short chromosome is called the Philadelphia chromosome
2) it so happens that the genes at this site on the chromosome code for creation of white blood cells (leukocytes)
3) so when the chromosome gets “squashed,” this causes disruption of normal coding, resulting in overproduction of leukocytes in the bone marrow & their release to the blood àextreme leukocytosis (too many white blood cells in blood)à leukemia.
4) CML diagnosis is “clinched” when a bone marrow sample is taken and the Philadelphia chromosome is seen in the WBCs.
5. staging
a. biopsies can both help to diagnose and then “stage” the tumor—ie, how far along it is in its growth—knowing the staging is important in treatment and prognosis.
b. note: there are several ways to stage—“TNM” staging is one example:
1) T= size of tumor.
| T0N0M0= essentially means a growth that is entirely benign. |
a) T0 = no cancer cells
b) T1- T3 = cancerous tumor size; increasing severity &
poorer prognosis with higher #.
2) N = extent of lymph nodes involvement.
a) N0 = no lymph node involvement.
b) N1- N3 = nodes involved (usually the ones closest to the
cancer site; increasing severity & poorer prognosis with higher #.
3) M = metastasis (“mets”) —spread to other tissues beyond local lymph nodes (ex: colon cancer spreading to liver)
a) M0 = no metastasis
b) M1- M3 = mets present; increasing severity & poorer prognosis with higher #.
6. classification / specific naming of tumors
a. benign tumors:
1) first part of name is usually the tissue involved
2) usually end in “oma,” meaning “tumor”
3) examples:
a) lipoma– benign fatty growth
b) leiomyoma: (“leio” = smooth, “myo” = muscle) benign tumor of smooth muscle
b. malignancies
1) malignancies are named according to cell type of origin like benign tumors, but in addition to “oma,” usually has root words “carcino” or “sarco,” or “blasto” there are quite a few exceptions
2) malignancies involving epithelial tissue usually have “carcinoma” plus organ of origin:
a) surface epithelium—carcinoma; ex– hepatocellular carcinoma; basal cell skin carcinoma. b) glandular tissue—add “adeno”– adenocarcinoma (benign tumor of gland would be adenoma)
3) malignancies involving connective tissue usually have “sarcoma” plus organ of origin
a) bone — osteosarcoma (osteo = bone) (benign bone tumor would be osteoma)
b) cartilage (chondro = cartilage) —chondrosarcoma
c) blood vessels – hemangiosarcoma (hemangio = blood vessel-related)
4) malignancies involving muscle tissue usually have specific muscle type plus “sarcoma” plus “myo”
a) smooth– leiomyosarcoma
b) striated (“rhabdo”), AKA skeletal muscle– rhabdomyosarcoma
5) malignant tumors involving neural tissue
a) usually have specific nerve type plus “blastoma” (“blast” refers to any cell that is very early in its development); b) ex—malignant tumor of nerve cell—neuroblastoma (benign nerve cell tumor would be: neuroma)
6) exceptions to malignancy naming rules
a) malignancy of lymph tissue called lymphoma; ex– Hodgkin’s lymphoma is NOT benign; it is a type of lymphatic cancer.
b) malignant skin cancer– melanoma
c) malignancy of hematological tissue: ex– leukemia (leuk = “white”)—cancer of WBCs (leukocytes); several categories, according to type of WBC & its stem cell origin
7. S&S: cancer can be in many body systems, and S&S will vary according to site, but there are certain clinical manifestations that can be generalized:
a. pain
1) initially there might not be pain, because many times malignant cells don’t “crowd” other cells—they actually kill off other cells & take over the space.
2) but eventually inflammation & nerve irritation in the area causes pain.
b. fatigue due in part to angiogenesis of tumor cells (tumor cells leech nutrition from normal cells by diverting blood supply).
c. cachexia (noun; “cachectic” – adjective) due to angiogenesis & other factors
1) a syndrome that includes anorexia, early satiety, weight loss, weakness, altered cellular metabolism
2) patients have sunken features & generally malnourished appearance
d. hematologic alterations such as anemia, leukopenia & thrombocytopenia
8. cancer treatment
a. radiation
b. surgery
c. vaccines against viruses like HPV.
d. chemotherapy—use of cytotoxic drugs
IV. Cellular Adaptation (note: though the lecture material often refers to “cellular” adaptation, injury, etc… also means “tissue” adaptation, etc, since cells make up tissues.)
A. Overview of adaptation
1. adaptation – process of accommodating to a new situation the body is undergoing, or creating a new state to accommodate changes in environment / situation ; can be temporary or permanent
2. can be in response to:
a. physiologic conditions– normal, as in when tissues of the uterus enlarge and increase in pregnancy
b. pathologic conditions—abnormal, as in when high blood pressure causes the heart to undergo enlargement because it has to work harder to maintain cardiac output in the “face” of more resistance.
B. Forms of adaptation
1. atrophy—decrease or shrinkage in cellular size
a. physiologic—occurs in early development; ex—thymus gland
b. pathologic
1) often occurs as result of decreases in “work load”—an area or an organ is no longer stimulated very much to do its “work,” so the cells shrink
2) ex—disuse atrophy
a) patient in bed for a long time or immobilized in some way b) having a cast, for example—those cells shrink up while
cast is on, then grow slowly back to normal when cast is off & the cells are “stimulate to “work” again.
2. hypertrophy—increase in size of cells & consequently size of organ
| FYI: Hyperplasia vs. Hypertrophy? Some cell types (nerve, heart, skeletal muscle) cannot increase rate of cell division. These cells only have the ability to increase in size as their workload is increased. |
a. caused by hormonal stimulation or increased functional demand, which results in accumulation of cellular proteins, NOT cellular fluid
b. physiologic examples:
1) heavy work, working outà hypertrophy of skeletal muscles
2) kidney removedà other kidney increases function & size of cells
c. pathologic example
1) hypertrophy of left ventricle: from trying to “fight against” hypertension (HTN)
2) cardiac hypertrophy is a good example of a compensatory response to a bad situation—as a larger muscle, the heart can overcome the resistance presented by HTN; eventually, though the heart can get TOO big and will decompensate (“poop out”)
3. hyperplasia—increase in number of cells resulting from increased rate of cell division
a. physiologic example– certain organs can regenerate using hyperplasia; ex—removal of part of liver leads to hyperplasia of liver cells (hepatocytes); even with removal of 70% of liver, regeneration is complete in 2 weeks.
b. pathologic hyperplasia— benign prostatic hyperplasia (BPH); as a man gets older, prostate enlarges from increase numbers of cells;
considered a pathology, yet is a very, very common problem in men
over 50-ish.
4. metaplasia—reversible replacement of one mature cell by another type of less differentiated (less specialized) mature cell; happens when cells are being subjected to chronic injury or irritation
a. ex–when normal columnar ciliated epithelial cells of bronchial linings in lungs of smokers are replaced by stratified squamous epithelial cells
b. begins to reverse & normalize as soon as the irritant (such as smoking) is removed
5. dysplasia —
a. abnormal changes in size, shape, & organization of mature cells due to persistent, severe cell injury or irritation
b. in some resources dysplasia is not considered a true “adaptive” process– consider it one step beyond “adaptation,” but not quite “cancer.”
1) sometimes called “pre-cancer” because the cells are much less differentiated than normal, but not quite as undifferentiated & disorganized as cancer cells.
2) remember, the less the differentiation = the lower the
function = the less specialized = the more likely to divide &
proliferate = more potential to be disorganized & cancer-like.
c. ex—PAP smears can reveal dysplastic cells of cervix that often must undergo laser-type treatment or close watching to make sure they do not deteriorate into a cervical cancer.
VI. Immobility
A. Definition; an alteration in mobility as a result of an acute (recent surgery, bone fracture, pneumonia, or new disease state) or chronic illness (sequela from a stroke/BA or long-standing disease).
1. Most disease and rehabilitative states involve some degree of immobility.
2. The longer a patient remains immobile, the greater the level of debilitation that will occur.
B. Potential Complications of immobility;
2. Musculoskeletal: muscle cells will shrink when no longer stimulated to do “much” work. Known as disuse atrophy.
| Complications from immobility can affect almost every system of the body. Throughout the semester, as specific disease states are identified and defined, the list of potential complications from immobility will grow. A concept map has been started; fill in the blanks as the semester progresses. At the end of the semester, compare your concept map answers with the completed concept map. The completed document will be available in “answers to learning resources” in “unit 5” material. |
C. Treatment/Nursing Interventions;
1. frequent repositioning / turning of bedbound patients
2. encourage early activity and ambulation
3. check skin for breakdown
4. use of protective devices for the skin, feet/heels/elbows
5. ensure adequate nutrition and hydration
6. educate patients and their families on the risks of immobility
| Nursing interventions are treatments or actions that are delivered to the patient by the nurse to ensure health or promote wellness. The nurse often uses his/her knowledge to determine which intervention will help a patient most. |
