-
Atrophy
decrease in number/size of cells
-
Metaplasia
change in cell type
-
Hyperplasia
increase in number of cells
-
Hypertrophy
increase in cell size (skeletal mm usually)
-
Dysplasia
when metaplasia or hyperplasia goes wrong
-
Injuries to cell that are reversible
-
1. Cell swelling
- 2. Bleb in cell membrane
- 3. Dispersion of ribosomes from ER
- 4. Clumping of chromatin
-
Injuries that are insurmountable causing cell death
-
1. Cytoplasmic changes
2. Nuclear changes (determinant of cell death)
-
Cytoplasmic changes (3 of them)
-
a. Homogenization of cytoplasm
- b. Cell particles break down
- c. mRNAs gone so no longer has blue tinge
-
2. Nuclear changes (determinant of cell death)
- a. Pyknosis=small, shrunken, hyperchromatic nucleus
- b. Karyorrhexis=nucleus that has broken apart (nuclear dust)
- c. Karyolysis=nucleus dissolves and disappears
-
Pyknosis
small, shrunken, hyperchromatic nucleus
-
Karyorrhexis
nucleus that has broken apart (nuclear dust)
-
Karyolysis
nucleus dissolves and disappears
-
-
a. Active, programmed cell suicide (physiologic event)
- b. Usually involves a single cell
- c. Breakdown of cell particles and packaged into membrane bodies
- d. Membrane bodies are taken up phagocytized by macrophages
- e. Since cell particles are never free in the environment there is no inflammation
-
-
a. Pathologic event
- b. Usually involves many cells
- c. Severe changes in environment cause irreversible cell injuryCell membrane torn apart and cytoplasmic content is exposed to environment leading to inflammation
-
1. Ischemic: poor blood supply causing hypoxia
2. Skin may ulcerate
3. Can still see cell boundaries
4. Dead cells will be replaced by regenerating cells or scar tissue
5. No nuclear contentDefined boundary between dead and alive tissues because only tissues that are supplied by the damaged blood vessels will die
Coagulative Necrosis
-
1. Ischemic
2. Wet gangrene=tissue gets infected
3. Dry gangrene= Desiccation of dead tissue on outer skin
a. Common in diabetics
4. Can occur on skin our internal organs
Gangrenous Necrosis
-
1. No underlying outline of tissue because it is dissolved
2. Necrotic tissue + inflammatory cells=abscess
a. e.g. whiteheadsCan’t heal like rest of body (no scar tissue), just leaves holes in tissue (cysts)
Liquefactive Necrosis
-
1. No identity of cells
2. Homogenous material with no underlying sense of architecture
3. Surrounded by lymphocytes and macrophages
4. When you see this the differential diagnosis is almost always tuberculosis
Caseous Necrosis
-
a. Lipases break down fat cells
b. Lipases abnormally activated in pancreas causes pancreatitis
c. Nondescript, chalky deposits
Enzymatic Fat Necrosis
-
a. Macrophages try to phagocytize fat because they see lipids as foreign
b. When they take in too much fat they rupture leaving behind a collection of fat that forms a mass
Traumatic Fat Necrosis
-
1. Doesn’t have gross appearance that shows abnormality because it has immune etiology
2. Occurs usually in the walls of vessels of small arteries and arterials
3. Presence within wall of pinkish stuff that looks like fibrin (hence fibrinoid)Decreases the size of the lumen of the vessel
Fibrinoid Necrosis
-
1. Serum calcium levels are normal but you get concentration of calcium in tissues leading to a calcium deposit in area of necrosis
2. Because it is solid, it can prevent organs, like the heart, from beating properly
Dystrophic Calcification
-
1. High serum calcium levels
2. May be due to hyperparathyroidism
3. Calcium is deposited in tissues to combat the high levels in serum
4. Can be monitored by serum calcium levelsMay prevent lungs from expanding
Metastatic Calcification
-
Most common type of cell injury
Metabolic
-
Metabolic Cell injury includes?
- Hypoxia/anoxia (most common cause of metabolic injury)
- Reactive Oxygen Species
-
Hypoxia/anoxia types
- Cardiovascular disease
- Pulmonary disease
- Anemia
- Hemoglobinopathies
- Ischemia (most common type of hypoxia)
- Loss of ATP production/lactic acid build-up
- Membrane ion pumps
- Activation of Ca dependent phospholipases
-
hemoglobin binds too tightly or not at all to oxygen
Hemoglobinopathies
-
difficulty perfusing tissues; causes nutrient deficiencies and accumulation of wastes
Ischemia (most common cause of hypoxia)
-
Loss of ATP production due to hypoxia/anoxia
- switch to anaerobic respiration
- Lactic acid build up
- Chromatin clumping
-
membrane ion pump failure due to hypoxia/anoxia
membrane becomes more permeable so sodium and water enters cytoplasm, causes swelling
-
activation of calcium dependent phospholipases due to hypoxia/anoxia causes
damage to cell membrane and autolysis
-
A. Are byproducts of normal metabolism; however they are toxic to cells
B. Anrioxidants break them down
C. Capable of structural alteration of proteins through inappropriate disulfide bonding – changes 3rd degree structure
D. Break down of cell membrane through Lipid peroxidation
Has the ability to directly damage DNA
Free Radicals (reactive oxygen species)
-
Types of mechanical trauma
- abrasion
- contusion
- laceration
- incision
- avulsion
- puncture wound
- penetration wound
-
frictional injury (ex – falling off bike on to concrete). Sometimes these are patterned (ex child abuse w/ electrical cord). Usually the injury is just partial ____ of the skin.
abrasion
-
bruise. Blunt force injury in which the skin is not broken but the underlying vessels are damaged and bleed. These can be dated by its color. As Hemoglobin is broken down it produces different pigments.
contusion
-
Caused by blunt force injury. Occurs on the body where the skin is right up against bone and so the skin splits from blunt force. Nerves & vessels stretch and can be visualized as stringy-intact material. stay in part. They can occur internally (ex. Spleen)
Laceration
-
1. caused by sharp instruments (scalpel or razor blade)
a. No jagged edge as in laceration; sharp instrument cuts through nerves and vessels
b. These will heal better than laceration; and with less scaring (doctors will usually make a laceration into this)
incision
-
tearing away of muscle or soft tissue (ex – hand being torn off)
Avulsion
-
wound from knife
puncture wound
-
Able to distinguish between entrance/exit wound by the shape and by the presence or absence of powder
Penetration wound
-
1. Increases free radical formation through interaction with water in cytoplasm;
2. it’s the secondary affect of free radicals that alters cellular activity (example given of PAP smear normally with round nuclei and proper nucleus/cytoplasm ratio; in abnormal cell there is irregular nuclei and not enough cytoplasm - looks similar to malignant cell)
3. Can cause acute changes (burns)
4. Can cause chronic changes (caused by scarring of arterial vessels; blood perfusion decreases and eventually leads to necrosis)
Ionizing Radiation (X-rays)
-
Hematopoietic syndrome (200-500 rads)
Gastrointestinal syndrome (500-1000 rads)
Cerebral syndrome (>2500 rads)
Systemic effects of ionizing radiation (X-rays) = we use ionizing radiation to therapeutically damage bone marrow.
-
(200-500 rads) – caused by moderate amount of exposure i. Bone marrow is very sensitive to radiation (In bone marrow transplant, radiation is used to ablate native bone marrow so transplanted bone marrow canengraft ii. In this syndrome all of the bone marrow elements are decreased (RBC, WBC, platelets)
Hematopoietic syndrome
-
(500-1000 rads) caused by exposure to more than moderate level of radiation Causes ulceration of --- mucosa leading to diarrhea and bleeding
Gastrointestinal syndrome
-
(>2500 rads) caused by over exposure to radiation (brain damage and death)
Cerebral syndrome
-
what sun burn is caused by
Non-ionizing radiation
-
(near by temperature decreases)
1. There are different phases of frostbite (Frostnip – superficial freezing of tissue, Superficial frostbite, Deep frostbite)
2. Digits and tip of nose are most susceptible
Localized hypothermia
-
can be fatal
1. When core body temperature drops, the brain actually interprets it as being hot (Deceased will be found with out clothes, because they think they are hot)
Systemic Hypothermia
-
are burns
1. Blisters caused by heat
2. 2nd degree burn – partial thickness burn
3. 3rd degree burns – full thickness burns; penetrates skin and goes into dermis (doesn’t hurt because you burn the nerve). Will hurt more once healing begins. There are problems with infection (leading to sepsis)
Localized hyperthermia
-
partial thickness burn
2nd degree burn
-
Blisters caused by heat
1st degree burns
-
full thickness burns; penetrates skin and goes into dermis (doesn’t hurt because you burn the nerve). Will hurt more once healing begins. There are problems with infection (leading to sepsis)
3rd degree burns
-
1. heat cramps
2. Heat exhaustion - still has ability to perspire; normal or subnormal temperature; moist clammy skin
3. Heat stroke (most severe) – lost ability to perspire; very high body temperature; dry hot skin
Systemic Hyperthermia
-
still has ability to perspire; normal or subnormal temperature; moist clammy ski
Heat exhaustion
-
lost ability to perspire; very high body temperature; dry hot skin
Heat stroke (most severe)
-
A. interrupts electrical activity of body (ability to breath, heart) will flow through without too much change
1. Skin has higher resistance than organs (more moist) to passage of electricity
2. Higher resistance causes burns
Electricity
-
low pressure to high pressure; visa versa (includes blast injuries from fireworks)
Atmospheric Pressure
-
side effects involved with ingesting drugs/chemicals (prescription and illicit)
Chemical/Drug injury
-
infections with microorganisms
Biological Injury
-
obesity; vitamin/protein deficiency
Nutritional Injury
-
type of Immunological injury
rheumatoid arthritis
-
Father of pathology, wrote a book 19th century “Cellular Pathology”
1. Disease previously thought to be result of “ill humors”Virchow – disease comes from malfunctioning of cells
Rudolph Virchow
-
These are needed for what?
A. Production of energy
B. Synthesis of protein
C. Maintenance of structure
Ability to replicate
cell viability
-
steady state can be changed by these? (3)
- physiological processes
- pathological processes
-
A. Change in cellular activity for a prolonged period of time
B. Basically an establishment of a new steady state in order to maintain viability. This can be physiologic or pathologic
Cellular adaptation
-
literally means no nutrition
caused by hormonal changes
Muscular dystrophy is this in muscle
atrophy
-
Hypertrophy signs
- § Fibers are thicker
- § Nuclei are bigger and rectangular (boxcar nuclei)
- § b/c cells can’t divide, they are forced to instead grow bigger
-
look of hyperplastic follicles
- a. architecture changes as cells pile up in number
- b. thyroid is being asked to send out more thyroid hormone which leads to enlargement of thyroid gland (goiter)
-
A. undergrowth
1. not an adaptation, it is a developmental failure to develop to adult size
------ kidney doesn’t function properly
hypoplastic
-
A. no growth
1. Developmental: failure to develop
Aplasia
-
Replacement of (columnar) epithelium of airways with squamous epithelium (squamous metaplasia)
metaplasia
-
irreversible change in tissue
neoplasia
-
i. Lined by stratified squamous epithelium, like the skin but without keratin layer
§ Basal epithelium: cells divide then migrate towards the surface
§ Then keratinize the cytoplasm, nuclei lay over, get smaller and are sloughed off the surface
§ Cells in the upper levels of the epithelium look like the cells in the basal layer (this is not good)The cells are thinking “the only way I can survive is if I don’t play by the rules”
cervical mucosa
-
Cells can express injury by accumulations of different kinds of material in the cytoplasm. This can result from:
- a. Increased production of normal cell products
- b. Inability to excrete normal cell products
- c. Interference with normal metabolic pathways
- d. Accumulation of abnormal metabolic products (if lacking an enzyme)
- e. Pinocytosis or phagocytosis of exogenous material
-
cloudy swelling (----- in the cytoplasm)
1. ----- vacuoles pushing the nuclei to the side (hydropic change) (very reversible)
Water accumulation
-
--- can accumulate in the cytoplasm of hepatocytes in the liver
a. Can be caused by alcohol use or infection
2. Stains to distinguish whether accumulation is water vs. ----
3. Yellow colored liver is possible indicator of lipid accumulation
---- infiltration (referring to the heart) ---- streaks growing into the myocardium – are not changes to the myocardium cells, is actually --- in between cells, does not really have any clinical significance
Lipid accumulation (fatty change / steatosis)
-
looks similar to other accumulations, differentiate using glycogen stain
Carbohydrate accumulation
-
1. intracellular hyaline (little red beady things)
a. hyaline (non specific term) means “stuff that stains pink / reddish, homogenous” and pretty much means that it is protein
b. renal tubular epithelial cells
2. extracellular hyaline
a. hyaline membrane disease
protein accumulation
-
a. hyaline (non specific term) means “stuff that stains pink / reddish, homogenous” and pretty much means that it is protein
b. renal tubular epithelial cells
intracellular hyaline (little red beady things)
-
hyaline membrane disease
extracellular hyaline
-
1. inhaled carbon pigment within lymphatics on the pleural surface of the lungs (anthrocosis) is not clinically relevant, we all have some degree of anthrocosis in our lungs
a. coal mine exposure can tear your lungs up however
exogenous pigment accumulation
-
1. brownish little knot globules in the heart, usually in a perinuclear position
2. becomes more apparent with age
3. we don’t know exactly what it is
4. we think it is from repeated membrane damage that has been repaired
5. often times in the heart it is present
a. in elderly there may be atrophy of the myofibers and the heart may take on a brownish discoloration because of accumulation of lipchromecan also be present in the liver
lipofucsin (lipochrome) pigment accumulation
-
a pigment (brown black pigment) that is produced by melanocytes
You can see accumulation of ------ on the skin
Melanin
-
1. (form of stored iron) is a byproduct of the breakdown of hemoglobin. It is a gold brown protein
2. Are found in reticuloendothelial cells that are responsible for removing abnormal red blood cells
Hemosiderin pigment accumulation
-
What color does hemosiderin stain
blue due to iron
-
hemosiderin can accumulate where?
in liver, pancrease, skin, and heart
-
a metabolic disorder in which there is a defect in normal iron metabolism.
a. Patients will have large amounts of iron in liver, pancreas, skin, and heart.
Can see that with this disorder the pancreas is a red color and when stained the pancreas turns blue due to high presence of hemosiderin
Hemochromatosis
-
1. a green brown color
a. It is also a byproduct of hemoglobin breakdown but does not contain iron
b. It can accumulate in fluid and tissue wherever there is disturbance in the uptake of ----- by hepatocytes such as a enzyme deficiency or when there is an obstruction of bile channels in the liver
2. The liver will turn a green color when bile accumulates
There will be increased -----in the blood and thus will see people’s eyes turn a yellowish color.
bilirubin (bile pigment accumulation)
-
Cytoplasmic changes
Eosinophilia and Homogenizaton
-
a. Will see that the cytoplasm turns pinker and is more homogenized (uniform in its composition)
b. Happen as a result of loss of cytoplasmic RNA and denaturation of cytoplasmic proteins
Eosinophilia
-
nucleus gets smaller
pyknosis
-
nucleus gets smaller and breaks up
Karyorrhexis
-
nucleus disappears
Karyolysis
-
Complications of Thrombosis that leads to sudden hypoxia and subsequent necrosis
1. Due to coagulation necrosis (except in brain-liquifactive necrosis)
Infarction
-
Things to consider about an infarction
- 1. Cardiovascular Status
- 2. Tissue sensitivity to hypoxia
- 3. Rapidity of occlusion
- 4. Vascular Anatomy
- a. Single Blood Supply
- b. Single Anastomosing blood vessel
- c. Dual Blood Supply
- d. Parallel Blood Supply( in in brain)
-
main vessel is occluded
results in prominent boundary line b/w necrotic and viable part of effected organ
pale infarction
-
A. Single vessel that branches to many vessels
B. Found in gut mainly
C. Protected from abrupt hypoxia due to alternate blood supply to same areaBleeding of alternate vessel into necrotic area leads to bleeding infarct (Hemmorrhagic Infarct)
Single Anastomosing Blood Supply
-
Two vessels that slight branch and supply blood to one areaAlso get Hemorrhagic Infarct here
Dual Blood Supply
-
A. Multiple vessels to get blood to same area
B. Usually found in brainOcclusions here may be less concerning because other ways to supply blood in area if one vessel get occluded
Parallel Blood Supply
-
Usually hemorrhagic infarctsDue to statsis or Thrombosis in vein
Infarcts from Venous Obstruction
-
Can arise during obstretic emergencies, malignancies, sepsis, major trama
Disseminated Intravascular Coagulation (DIC)
-
Steps of the Extrinsic and Intrinsic coagulation pathways that are activated at the microvascular level unnecessarily in Disseminated Intravascular Coagulation (DIC)
- 1. Coagulation factors and platlets are unnecessarily working
- 2. Fibrin and platlet thrombi formed consuming the platlets, fibrinogen, and coagulation factors and also activates the fibrinolytic system
- 3. Therefore coagulation factors are low systemically, but can’t just treat with coagulation factors bc will travel to site of microvascular occlusions.This leads to microvascular coagulation and simultaneous hemorrhaging
-
Extrinsic and Intrinsic coagulation pathways are activated at the microvascular level unnecessarily.
Billions of microvasculature are occluded with this problem
Disseminated Intravascular Coagulation (DIC)
-
Lab test results for DIC
Increased PT, Increased PTT, Decreased Fibrinongen, Increased Fibrin Split Product (FSP), Decrased Platlets.
-
a free floating mass that is carried through vasculatur to a point away from the point of entry
1. Most commonly from a thromboembolis, but can also be air, water, fat…
Embolus
-
2 types of Embolization
- Arterial Emboli (Systemic)
- Venous Emboli (Pulmonary)
-
A. 80-85% of these emboli are from mural thrombi in left ventricle and atrial.
B. Major parts these emboli infarct-brain, lower limbs, kidney, spleen.These infarcts appear wedge shaped with apex of triangle being the spot of occlusion
Arterial Emboli
-
A. 3rd most common reason for sudden death (after myocardial infarct and stroke)Caused by surgery, immobility, heart failure, pregnancy, obesity, muscle weakness, cancer, and stasis can all lead to
Venous Emboli
-
What's worse? one small venous embolus or shower of emboli
shower! (Can lead to pulmonary hypertension due to lack of perfusable vessels)
-
1. Can lead to dyspnea, anginal pain, syncope, venous distention of neck.
venous embolis
-
can lead to the above plus sudden tachycardia and hyperventilation
Occlusion of pulmonary artery
-
can lead to sudden death or diaphoresis (sweating from shock), sever dyspnea, cyanosis, tachycardia, anginal pain. Therefore larger veins, like femoral/iliac vein are concerning if become thrombolized.
Massive embolization, such as saddle-type
-
1. Hemorraghic coagulation necrosis ensues
2. Pleural effusion is also possible
characteristics of wedge shaped infarct
-
1. Increased D-Dimer Serum concentration can indicate fibrolysis of thrombus
2. Chest X-Ray can show pooling of blood
3. Pulmonary arteriography-most successful way
4. Decreased pCO2 due to the hyperventilationUsusally located in lower right lung lobe.
Diagnosing Emboli
-
body is made up of how much water
60%
-
Body is how much water in Extracellular
(20%)
-
Body is how much water in Intravascular (blood vessels)
(5%)
-
Body is how much water in Interstitial (Outside cells in ground substance of tissues)
(15%)
-
Body is how much water in Intracellular
(40%)
-
Localized accumulation of water
edema
-
-
Outside of the blood vessels
interstitial tissue
-
Forces acting on exchange between vasculature and interstitium
- Hydrostatic Pressure
- Osmotic pressure
- oncotic pressure
-
a. Force (like water pressure in hose) that pushes water out of vasculature and into the interstial space
b. Arteriole side: 35 mm Hg (water toward interstitial cells)
c. Venule side: 15 mm Hg
i. less than on arteriole side because water was pushed out into interstial cells therefore less pressure/hydrostatic when it comes out on venule side
Hydrostatic Pressure
-
a. Controlled predominately by Na+
b. Think concentration gradient: Greater amount of sodium in interstitial fluid so water leaves the vessel and goes into the interstitial space to balance out the Sodium concentration
c. Arteriole side: 5 mm Hg (water toward interstitial cells)
d. Venule side: 2 mm Hg
i. Less than on arteriole side because the sodium imbalance was fixed a little due to osmosis on arteriole side. (less difference in sodium concentration gradient on venule side)
Osmotic Pressure
-
a. Controlled by protein concentration in blood (therefore in vasculature)
i. Major source of protein in blood is albumin
b. Draws water back into vessels
c. Arteriole side: 20 mm Hg (water pulled into vasculature)
d. Venule side: 30 mm HgGreater than on arteriole side because protein can’t cross from vasculature to interstitium, and therefore it is concentrated when water left on arteriole side--due to hydrostatic (water out) + osmotic (water out) >oncotic (water in)
Oncotic Pressure
-
i. 35 mm Hg water out due Hydrostatic
ii. 5 mm Hg water out due to Osmotic
iii. 20 mm Hg water in due to Oncotic
iv. Overall: 20 mm Hg water out
Arteriole side
-
15 mm Hg water out due to Hydrostatic
2 mm Hg water out due to osmotic
30 mm Hg water in due to Oncotic
Overall: 13 mm Hg water in
Venule side
-
Arteriole pushes 20 mm Hg water out overall
Venule pulls in 13 mm Hg water in overall
7 mm Hg still left over on interstitial
What happens to this extra fluid left on interstitial side?
Arteriole and Venule balance
-
Carries off the extra fluid left on the interstitial side
lymphatic system
-
1. More sodium in interstital fluid
2. Draws more water out into interstitium
3. Causes
a. Decrease in renal function
i. Increased sodium intake is normally not a problem for younger people, the kidneys take care of it. But as people get older, their kidneys don’t work as well.
Increase in osmotic pressure
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