Patho - Term Test I Flashcards
How much body weight is water?
60% of total body weight
What are the two components of body fluids?
ICF (2/3 of TBW) and ECF (1/3 of TBW)
What consistitutes ECF (i.e. what are the components of ECF)
blood plasma (intravascular fluid), interstitial fluid, transcellular fluids (CSF, synovial fluid)
What is intersitital fluid?
Fluid that is found in spaces between cells but not within blood vessels
When is anaerobic glycolysis used?
When there is no oxygen present, cells use this method to breakdown glucose (pyruvate and lactic acid as byproducts)
- not a very efficient process (makes little ATP)
Define intravascular fluid
fluid found within blood vessels (aka blood plasma)
Define transcellular fluid and provide an example.
Fluid contained within epithelial-lined cavities of the body (smallest component of ECF)
ex. CSF, synovial fluid, urine, GI fluids, pleural fluids, pericardial fluids, peritonial fluids)
What are two methods in which you would inevitably lose fluids?
sweat and lung ventilation
Rank from greatest to least: water loss from these following methods
1) ventilation
2) stool
3) perspiration
4) renal excretion
renal > ventilation > perspiration > stool
What are the major cations and anions in ECF?
sodium (Na+)
chloride (Cl-)
What are the major cations and anions in ICF?
K+, phosphates and Mg2+
What forces move water between ICF and ECF
osmotic forces
Define Starling Forces. What are the 4 forces?
Forces that determine whether net effect is filtration or reabsorption
1) capillary hydrostatic pressure
2) capillary oncotic pressure
3) interstitial hydrostatic pressure
4) interstitial oncotic pressure
What does capillary hydrostatic pressure do?
facilitates water movement from capillary to interstitial space
What does capillary oncotic pressure do?
osmotically attracts water from interstitial spaces to capillary
What does interstitial oncotic pressure do?
osmotically attracts water from capillary to interstitial spaces
What does interstitial hydrostatic pressure do?
facilitates water movement from interstitial space to capillary
Which of the 4 starling forces promote fluid and proteins into lymphatics
interstitial hydrostatic pressure
True or false: Water, sodium and glucose move readily across capillary membrane
TRUE
True of False: albumin and other proteins move across capillary membrane to facilitate hydrostatic/oncotic pressures
False. They do not cross the membrane. Proteins stay in the capillary and generate oncotic pressures within plasma
Define filtration
movement of fluid out of capillaries and into interstitial space
Define reabsorption
fluid movement into capillaries from intersitial space
At the arterial end of capillary, is hydrostatic or oncotic pressure higher?
hydrostatic
At venous end of capillary, is hydrostatic or oncotic pressure higher?
oncotic
True or False: Typically intracellular and extracellular fluid osmotic pressures are equal, and water is equally distributed between interstitial and intracellular components
True
Which cation is responsible for osmotic balance of ECF?
Na+
Which cation is responsible for osmotic balance of ICF?
K+
What is edema?
excessive accumulation of fluid within interstitial spaces (fluid shifts from capillaries or lymphatic vessels –> interstitial spaces
What are the 4 causes of edema?
1) increased capillary hydrostatic pressure
2) decreased plasma oncotic pressure
3) increased capillary membrane permeability
4) lymphatic channel obstruction
How does increased capillary hydrostatic pressure cause edema? provide 2 explanations
1) venous obstruction (increased hydrostatic pressure behind the obstruction and fluid is pushed into interstitial spaces)
2) salt/water retention - causes volume overload leading to increased capillary hydrostatic pressure and edema
Provide two conditions that causes edema due to increased capillary hydrostatic pressure secondary to venous obstruction.
Any two:
- thrombophlebitis
- hepatic obstruction
- tight clothing around extremities
- prolonged standing
Provide a condition that causes edema due to increased capillary hydrostatic pressure secondary to salt/water retention
CHF, renal failure, liver cirrhosis
How does decreased plasma oncotic pressure cause edema?
due to decreased or loss of protein production (albumin) that typically holds onto water in blood vessels (so fluid remains in interstitial spaces)
Provide two conditions that causes edema due to decreased plasma oncotic pressure.
Any of these:
- protein malnutrition
- liver disease (reduced albumin production)
- glomerular diseases of the kidney
- serous damage from open wounds
- hemorrhage
- burns
- liver cirrhosis
How does increased capillary membrane permeability lead to edema?
proteins escape from within blood and into interstitial spaces which decreases capillary oncotic pressure so fluids are not pulled back into capillaries and protein buildup in interstitial fluid - typical in inflammatory responses
Provide two conditions that cause edema due to increased capillary membrane permeability
- trauma (burns/crush injuries)
- allergic reactions
- neoplastic diseases (conditions that cause abnormal cell growth)
How does lymphatic channel obstruction lead to edema?
if the channels are blocked it will lead to protein and fluid accumulation within interstitial space (cannot be drained) aka lymphedema (firm and non-compressible)
Provide two conditions that cause edema due to lymphatic channel obstruction.
any of the following:
- surgical removal of lymph nodes in arm/leg
- radiation therapy (can cause scar tissue formation that presses on the lymphatic channels)
- obstruction from malignant tumours
- infection
True or false: fluid accumulation does not affect nutrients and waste travelling through the capillaries and tissues
False. fluid accumulation increases distance they have to travel
Define pitting edema
When an indentation (pit) is left on the skin after being pressed
Define effusion
fluid accumulation within a body cavity or space
Severe generalized edema is also known as
anasarca
Dependent edema occurs when ______
fluid accumulates in gravity-dependent areas of the body (ex. legs and feet when standing)
How do you treat edema? Provide at least two interventions.
- diuretics
- elevation of swollen limbs
- compression stockings
- restricting salt intake
- IV albumin for severe cases
What systems regulate sodium, chloride, and water?
renal and endocrine systems
Sodium balance is regulated by _________ and ________; water balance is regulated by ___________
aldosterone, renal tubular reabsroption within kidney ; ADH
What three factors influence aldosterone secretion?
1) circulating blood volume
2) BP
3) plasma concentration of Na+ and K+
Describe how the renin-angiotensin-aldosterone system (RAAS) works when there is a decrease in blood pressure.
1) Decrease in blood volume or pressure causes renin to be secreted from juxtaglomerular cells in kidney
2) renin stimulates formation of angiotensin I
3) Angiotensin I converted to Angiotensin II by ACE
4) Angiotensin II is a vasoconstrictor so it increases BP by constricting blood vessels and renal perfusion is restored
5) Angiotensin II also stimulates aldosterone and ADH release to Na+ and water reabsorption, and K+ excretion –> blood volume increased
What are natriuretic peptides?
Hormones primarily produced by myocardium, natural antagonists of RAAS
What is the function of natriuretic peptides?
When increase BP is detected, natriuretic peptides cause vasodliation and increase Na+ and water secretion to decrease BP
ex. in CHF
True or false: changes in chloride concentration are proportionate to changes in sodium concentration
True
How does ADH (vasopressin) regulate water balance when plasma osmolality increases?
1) Increased plasma osmolality and circulating blood volume decreases (drop in BP) stimulate hypothalamus osmoreceptors that induce thirst sensation and ADH release
2) Increased fluid intake and water reabsorption in the distal tubules occurs
3) TBW increases
4) plasma osmolality decreases to normal
What are three common causes of dehydration?
excessive sweating, vomiting, inadequate intake
Where are volume-sensitive receptors found?
right and left atria; thoracic vessels
Where are baroreceptors found?
Aorta; pulmonary arteries, carotid sinus
Define isotonic fluid alterations
Changes in total body water with PROPORTIONAL changes of electrolytes
isotonic fluid loss causes (hypervolemia/hypovolemia)
hypovolemia
Four common causes of hypovolemia?
- hemorrhage
- severe wound drainage
- excessive sweating
- inadequate fluid intake
Which of the following is not a symptom of hypovolemia?
1) flat neck veins
2) increased HR, decreased BP
3) weight loss
4) increased urine output
5) dry skin and mucous membranes
increased urine output (output would actually decrease in hypovolemia)
What is the general treatment for hypovolemia?
Fluid replacement with isotonic solutions
- 0.9% normal saline
- 5% dextrose (D5NS)
- Ringer’s Lactate
- Pediatric oral replacement solution
- sports beverages
Isotonic fluid excess causes (hypervolemia/hypovolemia) as well as weight (gain/loss) and (increased/decreased) hematocrit and plasma protein concentration.
hypervolemia; gain; decreased
Common causes of hypervolemia?
- excess administration of IV fluids
- hypersecretion of aldosterone
- effect of drugs (i.e. cortisone)
Which of the following is a sign/symptom of hypervolemia?
1) neck vein distension
2) increased BP
3) edema
4) development of pulmonary edema and heart failure
5) all of the above
all of the above
Treatment for isotonic fluid excess (hypervolemia) includes:
diuretics
Define isovolemic hypernatremia.
When there is a deficit of free water accompanied by normal/near normal body sodium concentration
*the most common presentation of hypernatremia
Common causes of isovolemic hypernatremia:
inadequate water intake vomiting diarrhea excessive sweating burns resp. tract infections and fever (increased breathing leading to water loss)
*less common: diabetes insipidus (due to lack of ADH or inadequate response to ADH)
Define hypovolemic hypernatremia
When there is a loss of Na+ accompanied by a greater loss of water
Provide an example of a common cause of hypovolemic hypernatremia.
Any of the following:
- loop diuretics (increase water loss but inhibit sodium reabsorption)
- renal failure (can’t concentrate urine so loss of large volumes)
- diabetes-induced hyperglycemia (excess urinary solute that is non-reabsorable so water goes with it)
- osmotic diuretics (impairs renal concentrating capacity, ex. mannitol)
Define hypervolemic hypernatremia
When there is an increase in TBW with an even greater increase in Na+ level
All of the following cause hypervolemic hypernatremia except:
1) oversecretion of aldosterone or adrenoorticotropic hormone (ACTH)
2) vomiting
3) infusion of hypertonic saline solution in cases of salt depletion
4) Cushing syndrome
5) all of them cause hypervolemic hypernatremai
2) vomiting (does not cause hypervolemic hypernatremia)
Describe isovolemic hyponatremia
loss of Na+ without significant loss of water (purely just missing Na+)
Provide an example of a common cause of isovolemic hyponatremia.
- hypothyroidism
- pneumonia
- glucocorticoid deficiency (due to impaired renal free water clearance = diluted [Na+])
- water retention secondary to inappropriate ADH (SIADH)
- in those who are on low sodium diets + take diuretics
Treatment for isovolemic hyponatremia
vaptans (ADH receptor antagonists)
Describe hypovolemic hyponatremia
occurs when there is a loss of TBW but an even greater loss of Na+
Which of the following is not a common cause of hypovolemic hyponatremia?
1) prolonged vomiting
2) renal losses from diuretics
3) severe diarrhea
4) excess IV fluid administration
5) adrenal insufficiency (inadequate secretion of aldosterone)
excess IV fluid administration
Describe hypervolemic hyponatremia
An increase in Na+ levels but and even greater increase in TBW (dilution of Na+)
Provide a condition that causes hypervolemic hyponatremia
think fluid overload - edema usually occurs
- CHF
- liver cirrhosis
- nephrotic syndrome
Treatment for hypervolemic hyponatremia includes:
vaptans (ADH receptor antagonists)
Describe dilutional hyponatremia
- aka water intoxication
when large amounts of free water are taken in or if IV fluids (without salt so like dextrose in water) is given causing dilution in sodium
Which of the following is a common causes of dilutional hyponatremia?
1) tap water enemas
2) endurance sports (drinking lots of water, no eletrolytes)
3) compulsive water drinking
4) near drowning in fresh water
5) use of SSRIs
6) all of the above
all of the above
Treatment for dilutional hyponatremia includes
water restriction
True or false: hypokalemia is prevalent in elderly, those with alcoholism, and anorexia nervosa
True
Treatment of hypokalemia includes what?
Eaching potassium rich foods, replacement therapy to replace lost K+ and then treating underlying mechanism
Common causes of hyperkalemia include:
- increased intake of K+
- trauma to cell that causes shift of K+ from ICF to ECF
- decreased renal excretion/compromised renal function
- drugs that decrease renal K+ excretion (ACE inhibitors, angiotensin receptor blockers, aldosterone antagonists)
- burns & crush injuries (in response to severe burn/injuries, extra K+ is released in the blood)
- extensive surgeries (cells release extra K+ or from blood transfusions)
- insulin deficit (cannot faciliate uptake of K+ into cells)
- Digitalis toxicity (blocks Na-K ATPase pump so K+ can’t go into cells)
Treatment for hyperkalemia includes which of the following:
1) calcium gluconate (for cardiac membrane potential)
2) glucose administration
3) administration of K-binding agents
4) dialysis
5) all of the above
all of the above
- calcium gluconate helps stabilize cardiac membrane potential and therefore restores neuromuscular irritability)
- Glucose administration: stimulates insulin secretion to facilitate K+ uptake into cells
- administration of K-binding agents (and lower K+ levels)
- dialysis to remove excess K+ in cases of renal failure
Causes for hypophosphatemia
- malabsorption syndromes (long term alcohol use, vitamin D deficiency, use of Mg or aluminum containing antacids)
- respiratory alkalosis (increased pH causes increased cellular demands for phsophate so a fall in levels extracellularly)
- increased renal excretion of phosphate (associated with hyperparathyroidism)
Causes for hyperphosphatemia
- hypoparathyroidism (cannot inhibit phosphate reabsorption in the kidney)
- acute/chronic renal failure (cannot filter it out)
- treatment of metastatic tumours (chemotherapy because it releases large amounts of phosphate into serum)
- long term use of laxatives and enemas with phosphates
Which of the following are potential causes of hypomagnesemia?
1) malnutrition
2) malabsorption syndromes
3) alcoholism
4) urinary losses (loop diuretics, renal tubular dysfunction)
5) 1 and 3
6) all of the above
all of the above
Provide an example of a cause for hypermagnesemia.
- renal failure or insufficiency
- excessive intake of Mg-containing antacids
- adrenal insufficiency
What are volatile acids?
substances that can be eliminated through CO2 through lungs (ex. carbonic acid)
What are non-volatile acids?
substances that can be eliminated only by kidneys
Does the respiratory rate go up or down during acidosis?
up - trying to breathe off CO2
What is the definition of pathophysiology?
Study of underlying changes in body physiology resulting from disease or injury
What leads to metabolic acidosis?
increase in acid concentration or lost of bicarbonate in ECF (ratio is less than 20:1)
How does the body compensate in metabolic acidosis?
hyperventilate (Kussmaul’s respirations) and excrete H+
What leads to metabolic alkalosis
elevated HCO3- usually caused by excessive loss of metabolic acids (from vomiting or diuretics where you’re losing a bunch of ions specifically Cl-)
How does the body compensate for metabolic alkalosis
- suppress breathing
- kidneys try to excrete excess HCO3-
What leads to respiratory acidosis?
increased partial pressure of CO2 (hypercapnia) resulting from hypoventilation
How does the body compensate for respiratory acidosis
increase breathing to blow off CO2 and renal compensation by eliminating H+ and retention of HCO3-
What leads to respiratory alkalosis?
hyperventilation causes decrease in partial pressure of CO2 (co2 in blood)
How does the body compensate for respiratory alkalosis?
Slow down breathing, kidneys compensate by decreasing H+ excretion and bicarbonate reabsorption
True or False: Newborns are more susceptible to changes in TBW due to high metabolic rate and greater surface area
True
True or false: adaptation is a reversible response involving structural or functional modifications to accommodate both physiologic (normal) and pathologic (adverse) demands/conditions
true
sublethal cellular injuries are (reversible/irreversible) while lethal cellular injuries are (reversible/irreversible)
reversible; irreversible
What are the 8 common sources of cell injuries?
1) ischemic-hypoxic
2) ischemia
3) free radicals
4) reperfusion
5) immunologic
6) infectious
7) intentional/unintentional
8) inflammatory
What are the two main cell death types?
necrosis, apoptosis (and a third process - autophagy but not really cell death type)
Atrophy
shrinking in cell size
Common organs that are affected by atrophy?
heart, skeletal muscle, secondary sex organs, brain
Hypertrophy
increase in cell size (in response to mechanical load/stress)
Hypertrophy is common in which organs?
heart, kidney
Hyperplasia
increase in cell number (resulting from increased rate of cellular division, growth factors or increased output of new cells from tissue stem cells)
Metaplasia
reversible replacement of one mature cell type (epithelial or mesenchymal) by another cell type, frequently one less differentiated.
Lung cells being replaced in a long term smoker to cells that do not secrete mucus/have cilia is an example of what type of cellular adaptation?
Metaplasia
Dysplasia
- aka atypical hyperplasia
- abnormal/deranged cellular growth (changes in size, shape, and organization of mature cells)
- can be described as high grade or low grade
- Dysplasias that do not involve the entire thickness of epithelium may be completely reversible
Where is dysplasia commonly found?
in epithelial tissue of: uterine cervix, endometrium, GI and respiratory tract mucosa, also often found next to cancer cells (not indicative of cancer though)
When does cellular injury occur?
When cell is unable to maintain homeostasis
Which of the following in not a general mechanism of cellular injury?
1) ATP depletion
2) increased ROS
3) Ca2+ entry
4) mitochondrial/membrane damage
5) K+ entry
6) protein misfolding
K+ entry
How does reperfusion cause cellular injury?
1) increases oxidative stress (damages membrane and Ca+2 buildup)
2) calcium buildup (from damaged cell membrane + ROS-mediated injury lead to enhanced mito permeability leading to minimal to no ATP production)
3) inflammation (dead cells stimulate immune cells)
4) complement activation (exacerbates damage)
What is oxidative stress?
When there is a buildup of reactive oxygen species that exceeds antioxidant’s ability to detoxify
How does free radicals cause cellular injury?
the unpaired electrons are unstable so they try to stabilize self by forming bonds with proteins, lipids, and carbs and change a bunch of shit in the cells
leads to:
- lipid peroxidation (destroying lipids = damage to membrane)
- protein alterations
- DNA damage (mutations)
- mitochondrial dysfunction
What are xenobiotics?
compounds that have toxic, carcinogenic, or mutagenic properties that are found in an organism but not naturally produced within said organism
Signs and symptoms of lead poisoning include what? Treatment?
- GI symptoms (abdominal cramping, nausea, loss of appetite, weight loss)
- glucose, amino acids, and phosphates in urine
Treatment:
- removal of exposure source, chelation therapy (removes heavy metals from the body), correcting mineral deficiencies in the body
Lead poisoning in children can cause:
- cognitive deficits
- behavioural changes (antisocial behaviour, attention deficits)
- hyperpigmentation in gums
- children are most susceptible due to increased hand-mouth behaviour, blood brain barrier not mature yet, and infants absorb lead more than adults do
- also lead paint chips off the wall have sweet taste
Signs and symptoms of CO poisoning include:
tinnitus, nausea, vomiting, weakness, dizziness
Signs of FASD
microcephaly low birth weight cardiovascular defects growth retardation facial anomalies cognitive impairment ocular malformations
What substance causes the colour of periorbital ecchymosis?
hemosiderin
Mercury poisoning can negatively impact:
fetal brain development (if exposed during pregnancy)
How can mercury affect large groups of people?
climate change and thawing of frozen lands can release long stored mercury into bodies of water
True or false: Ethanol can lead to nutritional deficiencies
True
How does ethanol affect folic acid in the body?
1) decreased intestional absorption of folate
2) increased liver retention of folate
3) increased loss of folate through urine and feces
Describe blunt force injuries
Mechanical injury that results in tearing, shearing or crushing (blows, impacts, MVAs, falls)
What are contusions?
bleeding into skin or underlying tissues (aka bruises)
What is the typical trajectory of colour for contusions?
red-purple => blue-black => yellow-brown or green
Lacerations
tear/rip resulting when tensile strength of skin/tissue is surpassed (irregular abraded edges)
Avulsions
wide area of tissue pulled away
Incised wound
A wound that is longer than deep - more external bleeding than internal
Stab wound
A wound that is deeper than long - more internal bleeding, external bleeding may be small and wound may be closed by tissue pressure
Puncture wound
wound by sharp points but not sharp edges - prone to infection, can be deep
Chopping wound
heavy, edged instruments producing wounds that are a combination of sharp and blunt force injuries
Penetrating vs perforating GSW
Penetrating: bullet remains in body
Perforating: bullet exits body
- bullets can also fragment
What are the two most important factors when considering GSW and the severity of injury?
whether there is an entrance/exit wound and range of fire
Contact entrance wound
gun is held so muzzle sits on skin - obvious burn marks
Intermediate distance range entrance wound
usually gunpowder tattooing or stippling due to abrasion of skin from gun powder striking skin when it comes out of the barrel
indeterminate range entrance wound
when soot, gunpowder, etc. does not reach skin surface but bullet does (appearance is the same regardless of distance)
True or false: exit wound has the same appearance regardless of range of fire
true
*usually has clean edges and can reapproximate to cover defect
Wound potential of bullets depend on what?
depends on energy transferred to tissue impacted (Speed has much greater effect than size)
What are the four categories of asphyxial injuries?
Suffocation (choking asphyxiants)
strangulation (hanging, ligature, manual strangulation)
chemical asphyxiants (cyanide, hydrogen sulfide)
drownings
Suffocation
process of dying as a result of lack of oxygen (lack of O2 in the environment such as methane, or blockage of respiratory airways)
When does choking asphyxiation occur?
when there is an obstruction of pulmonary airways (i.e. lodged object or airway swelling)
What are the two main signs that indicate choking asphxyiation?
petechiae (small capillaries breaking leading to red points on skin - due to obstruction of blood flow back to heart), florid facial congestion
Strangulation is caused by
compression of blood vessels and air passages resulting from external pressure on the neck
True or false: in strangulation, people typically die due to lack of airflow
False - it’s due to no blood flow to the brain
Hanging strangulation vs. ligature strangulation
Hanging strangulation - inverted V shape ligature mark, patient has severe soft tissue injury and c-spine trauma (petechiae in eyes/face)
Ligature strangulation - no suspension, some form of cord tightens around neck (petechiae common due to intermittent releasing of ligature during struggle)
Manual strangulation is defined as
use of hands to compress neck of victim to point where death by asphyxiation occurs
- usually noted with external neck trauma and internal damage (bruising to deep structures, fractures), petechiae
How do chemical asphyxiants cause asphyxiation?
they prevent deliver of O2 to tissues or block O2 use
Provde 4 examples of chemical asphyxiants
methane, CO, hydrogen sulfide, cyanide
cyanide poisoning has what presentation?
cherry red colouration to skin and mucus membrane; smells like almonds
Patients who have suffered from hydrogen sulfide (sewer gas) asphyxiation will present with what?
- brown tinged blood
- signs of asphyxiation
- rotten egg smell
True or False: Methane displaces oxygen, causes asphyxiation
True
Define: drowning
lack of oxygen delivery from inhalation and suffocation by a liquid (hypoxemia)
What is dry lung drowning?
when little to no water enter the lungs during drowning (due to airway being closed off)
- caused by vagal nerve mediated laryngospasms that close off airway
The virulence of a microorganism is determined by what two factors?
It’s ability to SURVIVE and PROLIFERATE in the human body
Disease-producing potential of microorganisms depends on what three things?
1) ability to invade and destroy cells
2) produce toxins
3) produce damaging hypersensitivity reactions
Inflammatory or immunologic injuries to the cell cause cell membrane alterations. True or False
True
- leak K+ out of cell
- influx of water
- antibodies bind with receptors and interfere with its function
- antibodies block cellular junctions (cells can’t communicate)
Define extravasation
leakage of fluid out of its normal region into surrounding areas where it doesn’t belong
True or False: Accumulation in calcium salts is a sign of physiologic or pathologic change
False. Cellular calcification only occurs in pathologic changes because it only ever occurs in injured or dead cells (not normal processes therefore not physiologic)
Disturbances in urate metabolism lead to what?
Gout
Systemic manifestations of cellular injury include all of the following but:
1) fever
2) pain
3) increased HR
4) presence of cellular enzymes
5) leukopenia
6) all of the above are correct
leukopenia
The following are systemic manifestations of cellular injury:
- fever (endogenous pyrogens)
- increased HR (increased oxidating metabolic processes resulting from fever)
- pain (from obstruction, pressure, bradykinin)
- cellular enzymes (released into ECF)
- leukocytosis (bc infection)
Define necrosis
Death of cells characterized by rapid loss of plasma membrane structure, organelle swelling and dysfunction, and lacking of typical features of apoptosis
Apoptosis
programmed cell death (orderly dismantling of cell contents and packaging remainders in vesicles)
What are the 4 major types of necrosis
Coagulative
Liquefactive
Caseous
Fatty
Gangrenous Necrosis
not type of necrosis but refers to large areas of tissue death
Coagulative necrosis
Area of cell death in which protein denaturation turns proteins into firm and opaque (from gelatinous transparent state)
Infarct
area of coagulative necrosis
Coagulative necrosis often found in which organs?
kidney, heart, adrenal glands
Liquefactive necrosis
When cells are digested by their own hydrolases causing tissue to be soft and runny; cyst formation also occurs
Where is liquefactive necrosis commonly found?
In dead brain cells (due to ischemic injuries to neurons and glial cells) AND brain cells are rich in digestive enzymes and lipids
Liquefactive necrosis is usually cause by what?
Bacterial infection (e. coli, strep, staph)
Caseous necrosis
Area of cell death where dead cells disintegrate but debris not completely hydrolyzed (combo of liquefactive and coagulative necrosis)
Caseous necrosis is commonly caused by
pulmonary TB or infection caused by TB
What does caseous necrotic tissue look like?
soft, granular tissue (looks like clumped cheese)
also often granuloma formation
Fatty necrosis
area of cell death where cellular dissolution is caused by lipases releasing fatty acids
What does fatty necrotic tissue look like?
Chalk white and opaque
Saponification happens in what type of necrosis?
Fatty necrosis (fatty acids combine with Ca, Mg, and Na ions creating soaps)
What is the typical cause of gangrenous necrosis?
hypoxia + bacterial invasion
Dry gangrene vs. wet gangrene
Dry gangrene: result from coagulative necrosis –> dry and shrinking skin, colour is dark brown-black (ex. of cause: diabetes and poor circulation)
Wet gangrene: develops when neutrophils invade site causing liquefactive necrosis
What does tissue look like in wet gangrene?
tissue becomes cold, swollen, black, foul odor, and death
What is gas gangrene?
type of wet gangrene caused by infection of injured tissue by Clostridium (anaerobic bacteria destroys cell membrane and causes gas bubbles to form leading to rapid infection/sepsis, renal shutdown, and potential death
When would apoptosis occur pathologically? (4)
from:
1) severe cell injury - can’t be revived sorry
2) accumulation of misfolded proteins
3) infections (host says let’s destroy cell bc virus is here)
4) obstruction in tissue ducts - blood cannot flow to an organ
What are the enzymes that trigger protein breakdown and subsequently apoptosis?
caspases
What is autophagy?
Eating of self
When would autophagy occur?
when cells are starved or don’t have nutrients (so digest the cells and recycle contents for better use)
True or false: autophagy declines and becomes less efficient as cells age
True - contributes to aging process
Aging
Normal physiologic processes that are universal and inevitable (gradual loss of homeostatic mechanisms)
True or False: Aging is considered a disease.
No, it’s a natural normal process so this is false
Life span vs. life expectancy
Life span - period from birth to death
Life expectancy - avg number of years of life remaining at a given age
Sarcopenia
loss of muscle mass and strength as we age
True or False: Cells, tissues, and body systems age and extracellular changes all occur as we get older
True
Frailty is characterized by: (3 things)
overall weakness, decreased stamina, and functional decline
Somatic death
Death of the entire body
Postmortem changes
changes that occur after death
Pallor mortis
1st stage - skin becomes pale and yellowish
Algor mortis
2nd stage - body temperature drops because heart is not pumping (usually falls to temp of the environment)
Rigor mortis
3rd stage - stiffening of muscles (within 6 hours of death)
- happens due acidic compounds accumulating within muscles from to contractile proteins failing leading to muscle rigidity
- smaller muscles usually affected first (like the jaw)
Livor mortis
4th stage - gravity causes blood to settle in most dependent/lowest tissues developing purple discolouration
Postmortem autolysis (aka putrefaction)
Tissues and organs lose cohesiveness as they breakdown into gaseous and liquid matter (24-48 post death)
Signs of putrefaction include:
- greenish discolouration of skin (eventually turns black)
- swelling and bloating due to gas build up
- organs begin to liquefy
- rate depends on environmental temp
Atrophy of the thymus gland is classifised as what type of atrophy?
physiological (i.e. occurs with early development, normal)
Atrophy in a limb after being placed in a cast is known as:
disuse atrophy
Pathologic atrophy occurs when?
decreases in workload, pressure, use, blood supply, nutrition, and hormonal/neuronal stimulation
- disuse atrophy would also fall under this category
Physiological vs pathologic hypertrophy
Physiologic: from increased demand, stimulation by hormones, and growth factors
Pathologic: chronic hemodynamic overload (hypertension) leading to contractile dysfunction and then heart failure
True or false: cellular adaptations usually only work short term and cannot withhold long term stressors
True (long term stressors will overwhelm adaptive process leading to cell injury/death)
There are two types of physiological hyperplasia. What are they and give an example of each.
Compensatory hyperplasia: enables organs to regenerate (i.e. liver, calluses, wound healing secondary to inflammation process)
Hormonal hyperplasia: occurs in organs that respond to endocrine hormonal stimulation (follicular phase of menstrual cycle where estrogen secretion causes endometrial proliferation)
What is pathologic hormonal hyperplasia? Provide 3 examples.
abnormal proliferation of normal cells usually in response to excessive hormone stimulation or growth factors
ex. BPH - benign prostate hyperplasia
- thyroid goiters
- pathology hyperplasia of the uterine endometrium
S/Sx of pathologic hyperplasia of uterine endometrium include:
erratic/excessive bleeding (aka dysfunctional uterine bleeding)
- due to imablance between estrogen and progesterone levels
- may lead to malignancy and endometrial cancer if not treated
List the steps in which cellular injury leads to hydropic degeneration.
1) injury leads to hypoxia
2) ATP production decreases
3) Na+ and H2O moves into cell, K+ moves out of cell
4) osmotic pressure increases
5) more water moves into cell
6) cisternae of ER distend, rupture and form vacuoles
7) extensive vacuolation
8) hydropic degeneration
What is the single most common cause of cellulary injury?
ischemia and hypoxic injury (and ischemia is the most common cause of hypoxia)
Ischemia and hypoxic injury results from what causes?
- reduced amount of O2 in the air
- loss of Hb or decreased efficacy of Hb
- Decreased RBC production
- Resp. or CV diseases (arteriosclerosis)
- Poisoning of oxidative enzymes (cytochromes) within cells
Define vacuolation
formation of vacuoles aka storage bubbles found in cells (within cytoplasm)
What processes are happening during ischemic and hypoxic injury?
Blood supply interrupted leading to heart dysfunction and unable to contract normally
- within 3-5 minutes, mitochondria doens’t function properly –> insufficient ATP production –> heart can’t contract because of lack of ATP –> anaerobic metabolism until glycogen stores are depleted –> Na-K pumps now cannot work because they need ATP to function –> Na+ and Ca+2 go into cell while K+ diffuses out –> K+ swells –> vacuolation
Reperfusion injury and reactive oxygen readicals ultimately lead to ______.
necrosis
What is ROS (reactive oxygen species)?
reactive molecules from molecular oxygen formed as a natural oxidant species in cells during mitochondrial respiration and energy generation –> cause oxidative stress
What sources/causes lead to free radical formation?
- redox reactions
- absoprtion of extreme energy sources (UV, radiation)
- metabolism of exogenous chemicals/drugs (substances in the environment like CCl3)
- transition metals (iron, copper)
- nitric oxide
Biotransformation
a process whereby enzymatic reactions convert one chemical into a less toxic or nontoxic compound (happens a lot in the liver when chemicals/drug enter the body)
What are antioxidants?
molecules that inhibit oxidation of other molecules to prevent formation of free radicals
The leading cause of poisoning in children is what?
medications (including inappropriate administration of over the counter preparations of acetaminophen)
The most common site for chemically induced injury is:
liver
The single largest environment health risk is
air pollution
True or false. Lead (Pb) in the body leads to increased oxidative stress and is found commonly in older homes, workplaces, and in the environment
True
Symptoms of arsenic poisoning include:
Acute GI, CV, and CNS toxicities (often fatal)
- chronic exposure could lead to skin lesions (hyperpigmentation, hyperkeratosis) and cancer (lung, bladder)
Cadmium poisoning presents with:
- obstructive lung disease
- renal tubule damage
- skeletal abnormalities with calcium loss
- osteoporosis and osteomalacia in post-menopausal women
*cause: toxicity due to ROS generation
Major nutritional deficiencies with alcohol abuse include what?
vitamin B6, Magnesium, thiamine, folic acid, phosphorus
Binge drinking is defined as how many drinks for men and women?
Binge drinking , defined as four standard alcoholic drinks on one occasion for women and five drinks for men
Unintentional/intentional injuries are more common in:
men
What is the difference between hematoma, subdural hematoma, and epidural hematoma?
Hematoma: collection of blood in soft tissue
Subdural: blood between inner surface of dura mater and surface of brain
Epidural hematoma: collectino of blood between inner surface of skull and dura
Hard contact gunshot wounds (ex. GSW to the head) can cause what?
severe tearing and disruption of tissue leading to jagged and gaping wound (blow back)
What is the most common chemical asphyxiant?
carbon monoxide
Accumulations (infiltrations) of substances in cells are caused by four general types of abnormal mechanisms. What are they?
1) insufficient removal of normal substance because of altered configuration or transport
2) accumulation due to protein folding defects, transport, or abnormal degradation
3) inadequate metabolism of an endogenous substance (usually because of lack of enzyme)
4) harmful exogenous materials
Excess cellular water accumulation leads to what?
- cellular swelling and pallor
- vacuolation
Excess cellular lipid/carb accumulation leads to what?
- neuro deficits
- progressive disorders
- vacuolation pushes organelles to the side
- common in spleen, liver, CNS
Excess cellular glycogen accumulation leads to what?
- glycogen storage disease/diseases affecting glucose and glycogen accumulation
- vacuolation
- detrimental to growth and development
- seen in diabetes
The most immediate manifestations of somatic death is:
Complete cessation of respiration and circulation
Excessive cellular protein accumulation leads to what?
- crowds organelles which disrupt function and intracellular communication
- primarily accumulates in epithelial cells of renal tubules, B lymphocytes
- may reuslt in proteinuria
What is melanin
brown-black pigment derived from tyrosine amino acid and synthesized by melanocytes; stored in melanosomes
Albinism
congenital inherited disorder characterized by complete or partial absence of melanin (high risk of skin cancer)
What are hemoproteins?
essential endogenous pigments (Hb, cytochromes)
Hemosiderosis
transient localized deposit or iron (where bruising occurs); blood vessels ruptured
Degradation of Hb in bruises changes in to a variety of colours.
Which pigments are responsible for the following?
1) red-blue
2) green
3) yellow
4) golden brown
1) hemoglobin
2) biliverdin
3) bilirubin
4) hemosiderin
Iron is stored in the tissue cells in two forms. What are they?
Ferritin
Hemosiderin (yellow brown pigment)
Iron overload is also known as
hemachromatosis
Jaundice (icterus) is caused by what pigment in excess?
bilirubin
Define extravasation
The leakage of blood, lymph, or other fluid, such as an anticancer drug, from a blood vessel or tube into the tissue around it.
What is dystrophic calcification
calcification occurring in dying/necrotic tissues (common in chronic pulmonary TB; also in lymph nodes, advanced atherosclerosis, injured heart valves)
- in heart valves, it presents as a heart murmur
What is metastatic calcification
mineral deposits occuring in undamaged, normal tissues secondary to hypercalcemia
Describe the following features of a cell undergoing necrosis:
1) cell size
2) nucleus
3) plasma membrane
4) cellular components
5) adjacent inflammation
6) physiologic or pathologic role
1) cell swelling
2) nucleus shrinks (pyknosis) which fragments into nuclear dust (keryorrhexis) and then finally breaksdown of chromatin (karolysis)
3) membrane disrupted
4) cellular contents digested and may leak out of cell
5) frequent adjacent inflammation
6) always pathologic
Describe the following features of a cell undergoing apoptosis:
1) cell size
2) nucleus
3) plasma membrane
4) cellular components
5) adjacent inflammation
6) physiologic or pathologic role
1) cell shrinking
2) fragmentation to nucleosome-size fragments
3) intact but altered plasma membrane
4) intact cell contents, may be released in apoptotic bodies
5) no adjacent inflammation
6) often physiologic role but may be pathologic wih some cell injury types
True or false. Cells die long before any necrotic changes are noted.
True
What is dysregulated apoptosis?
excessive or insufficient apoptosis (can be malfunctioning and encourage survivial of abnormal cells or lead to autoimmune disorders)
What are the major forms of autophagy?
Macroautophagy: aka “autophagy” and is where cytosol parts are sequestered and transported in a vacuole
Microautophagy: inward invagination of lysosomal membrane for cargo delivery
Chaperone-mediated autophagy: chaperone-dependent proteins that direct cargo across lysosomal membrane
Senescence
process leading to permanent proliferative arrest of cells in response to various stressors
What degenerative extracellular changes occur with aging?
- binding of collagen
- increased free radicals
- alterations to MSK system
- development of CV diseases, oxidative stress
What occurs during cellular aging?
- atrophy, decreased function, loss of cells
- compensatory mechanisms: hypertrophy/hyperplasia
- damage to cell memebrane, genetic material, progression of common diseases (cancer, diabetes, heart failure)
What occurs during tissue and systemic aging?
- progressive stiffness and rigidity (affects arterial, pulmonary, and MSK)
- sarcopenia
A patient presents with increased susceptibility to falls, disability, disease and death. A general term to describe this syndrome is called?
frailty syndrome
Which of the following male-female differences re: aging is true?
1) men have more muscle muss so may be protective against frailty
2) testosterone and GH can provide advantages to men re: muscle mass maintenance
3) cortisol is dysregulated especially in older women
4) all of the above are true
all are true
Define cachexia
weakness and wasting of body due to severe chronic illness
Define decomposition
body organic matter broken down into elemental matter to be recycled into the earth
Define skeletonization
final stage of death (7th stage) where skeleton is exposed due to body degradation and decay
Define fossilization
rare 8th stage, bones are infiltrated and replaced with inorganic mineral deposits
What is the net filtration equation?
forces favouring filtration - forces opposing filtration
Cerebral, pulmonary, and laryngeal edema are common examples of (localized/generalized) edema.
localized
True or false. Edema causes wounds to heal more slowly and increase risk of infection or decubiti.
True
The region where edematous fluid accumulates is referred to as:
a third space (interstitial space)
- fluid trapped here cannot be used for metabolic processes or perfusion
True or False. A patient could be dehydrated as a result of edema
True - due to fluid being sequestered
What sorts of drug therapy are used for hypertension?
ACE inhibitors
angiotension receptor blockers
renin inhibitors
^ all of those are blocking substances that are released in the body to increase BP
What are the three types of natriuetic peptides?
1) Atrial Natriuretic Peptides (ANH)
2) B-type natriuretic peptide (BNP)
3) Urodilation (ANP analogue)
[Cl-} is inversely proportionate to what?
[HCO3-]
What do volume-sensitive receptors and baroreceptors do?
sense changes in blood pressure and volume (such as during dehydration)
True or false. Hyperchloremia is inversely related to hypernatremia.
False. [Cl-] typically follows [Na+] so if one is elevated, so will the other
Signs and symptoms of dehydration include all of the following except:
1) decreased skin turgor
2) elevated temperature
3) prolonged capillary refill time
4) bradycardia
5) soft eyeballs
6) sunken fontanels in infants
7) weak pulses
bradycardia (heart rate will actually increase with dehydration)
What is the pathophysiology behind hypernatremia?
elevated serum Na+ levels (above 145 mEq/L) leading to hypertonicity and intracellular dehydration
Treatment for isovolemic hypernatremia
- water PO
- IV dextrose 5% in water
- 0.45% NS solution
Treatment for hypovolemic hypernatremia
- oral fluids
- salt-free IV (dextrose 5% in water)
- slow fluid replacement to prevent cerebral edema
Treatment for hypervolemic hypernatremia
loop diuretics and treating underlying condition
Why are CNS signs the most serious in hypernatremia?
Due to alterations in membrane potentials and shrinking of brain cells
What is the pathophysiology behind hyponatremia?
decreased serum Na+ levels (<135 mEq/L) due to loss of sodium, inadequate intake, or water excess leading to dilution of sodium
- cell will swell and rupture
What electrolyte imbalance is a major cause of morbidity/mortality in ICU and elderly?
hyponatremia, contributing factors:
- due to use of diuretics to increase urine flow
- dehydration (from decreased thirst)
- diminished urine concentrating ability
- age related changes and diseases
How does decreased [Na+]/hyponatremia manifest (i.e. signs and symptoms)?
- cerebral edema (inreased intracranial pressure
- impaired nerve conduction and neurological changes)
- cognitive deficits
- gait disturbances
- falls with fractures
Which ion maintains the resting membrane potential, facilitates glycogen and glucose deposition in liver/skeletal muscle cells, and maintains normal cardiac rhythm in skeletal/smooth muscle contraction?
K+
The most significant regulator of K+ is:
kidney (and then also regulated by aldosterone &insulin)
How does [K+] get influenced by acute acidosis/alkalosis?
Acute acidosis: accumulation of H+ in ICF so K+ shifts out to maintain ionic balance, which leads to less K+ being secreted by distal tubular cells and inrease hyperkalemia risk
Acute alkalosis: dereased H+ in ICF so K+ shifts into cell, K+ secretion also inreases within distal tubular cells leading to increased hypokalemia risk
How does aldosterone regulate increased potassium levels?
1) increased potassium stimulates release of renin by JG cells in kidney leading to aldosterone release
2) aldosterone stimulates secretion of K+ into urine by distal renal tubules and also increases K+ secretion from sweat glands
How does insulin regulate K+?
insulin is released after eating which drives K+ uptake into liver and muscle cells by stimulating Na-K ATPase pumps (therefore can be used to treat hyperkalemia)
Define potassium adaptation
ability for body to adapt to increased levels of K+ intake over time
Common causes of hypokalemia?
- reduced intake or increased losses of K+
- increased movement of K+ into cells
- during treatment of diabetic ketoacidosis (K+ moves out of cell due to H+ accumulation in ICF, K+ then gets excreted or taken up via insulin stimulation)
- renal/GI disorders
- vomiting or NG suctioning (loss of other ions lead to renal compensation, stimulating aldosterone release to take up other ions back into the body, thus excreting potassium)
- K+ wasting diuretics
- low plasma [Mg2+]
- certain antibiotics or rare herditary defects
What are symptoms of hypokalemia?
Mild K+ losses are asymptomatic
Severe K+ losses: neuromuscular and cardiac disorders
- skeletal muscle weakness (may lead to diaphragm weakness = respiratory arrest)
- various dysrhythmias due to resting membrane potential disruptions
- metabolic dysfunctions
How does a patient with hyperkalemia present?
mild: increased neuromuscular irritability (restlessness, intestinal cramping, diarrhea)
severe: decreased resting membrane potential so muscle weakness, loss of muscle tone, paralysis, V-fib, cardiac arrest
- delayed cardiac conduction
- bradydysrhythmias
Effects of hypophosphatemia
- reduced capacity for O2 transport by RBC (disturbed energy metabolism)
- leukocyte and platelet dysfunction
- deranged muscle and nerve function
- severe: irritability, respiratory failure, convulsions, confusion, numbness, coma
Effects of hyperphosphatemia
- Sx related to low Ca+ levels so similar to hypocalcemia
- when prolonged: calcification of soft tissues in lungs, kidneys and joints
A patient presents with muscle cramps, ataxia, nystagmus, and tetany with a history of alcoholism is likely suffering from what electrolyte imbalance?
hypomagnesemia
Signs and symptoms of hypomagnesemia?
- skeletal smooth muscle contraction
- excess nerve function
- loss of deep tendon reflexes
- nausea/vomiting
- muscle weakness
- hypotension
- bradycardia
- resp distress
A base (accepts/donates) H+ An acid (accepts/donates) H+
base: acccepts
acid: donates
Chemical buffer systems include what?
The chemical buffering system has an _________ response.
bicarbonate, phosphate, Hb, and protein
immediate
Respiratory buffering system responds within:
minutes to hours
Renal buffering system responds within:
hours to days
At 7.4 pH, the ratio of bicarbonate to carbonic acid (BB/CA) is:
20:1
Define compensations re: acid base balance and BB/CA
adjustments of pH (so BB/CA) to maintain 20:1 ratio
Bicarbonate, phosphate and ammonia buffers work in which buffering system? Chemical, respiratory, or renal?
Renal
Briefly describe phosphate buffer mechanism in renal system.
monobasic phosphate (H2PO4-) and dibasic phosphate (HPO42-) work with Na+ to form a sodium salt, monobasic phosphate released into urine
Briefly describe ammonia buffer mechanism in renal system.
ammonia (NH3) and ammonium (NH4+) reversibly bind or release H+ into urine
- NH4+ released into urine
Acidemia
arterial blood pH < 7.4
Alkalemia
arterial blood > 7.4 pH
Common causes of respiratory acidosis
- respiratory depression by drugs, head injury
- paralysis of respiratory muscles
- chest wall disorders
- lung disorders (pneumonia, pulomnary edema,, emphysema, asthma, bronchitis)
Common causes of respiratory alkalosis
- hypoxemia from pulmonary disease, CHF, high altitudes
- hypermetabolic states (fever, anemia, hysteria, cirrhosis, grem-negative sepsis)
- improper use of mechanical ventilators
Signs and symptoms of respiratory acidosis include all of the following but:
1) warm, flushed skin
2) initial rapid breathing rate and then gradually more depressed
3) muscle twitching/tremors/convulsions
4) paresthesia
paresthesia
Signs and symptoms of respiratory alkalosis include all of the following but:
1) carpopedal spasms (spasms of han n feet)
2) cebral vasodilation
3) paresthesia
4) confusion and dizziness
2) cebral vasodilation
what happens during respiratory alkalosis is cerebral vasoconstriction which then reduces cerebral blood flow
Why are infants more susceptable to significant changes in TBW?
due to high metabolic rate and greater body surface area
What causes % of TBW to decline with geriatrics?
- decreased free fat mass and muscle mass
- reduced ability to regulate Na+ and water balance
- kidneys less efficient at producing concentrated urine
- sluggish sodium conservation responses
- thirst perception impaired
- loss of cog function can influence fluid intake
