MS1, Block 2 Cell/Tissue Injury

Atrophy

Metaplasia

Hyperplasia

Hypertrophy

Dysplasia

Injuries to cell that are reversible

1. Cell swelling

Injuries that are insurmountable causing cell death

1. Cytoplasmic changes

Cytoplasmic changes (3 of them)

a. Homogenization of cytoplasm

2. Nuclear changes (determinant of cell death)

Pyknosis

Karyorrhexis

Karyolysis

Apoptosis

a. Active, programmed cell suicide (physiologic event)

Necrosis

a. Pathologic event

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

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

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)

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

a. Lipases break down fat cells
b. Lipases abnormally activated in pancreas causes pancreatitis
c. Nondescript, chalky deposits

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

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

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

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

Most common type of cell injury

Metabolic Cell injury includes?

Hypoxia/anoxia types

hemoglobin binds too tightly or not at all to oxygen

difficulty perfusing tissues; causes nutrient deficiencies and accumulation of wastes

Loss of ATP production due to hypoxia/anoxia

membrane ion pump failure due to hypoxia/anoxia

activation of calcium dependent phospholipases due to hypoxia/anoxia causes

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

Types of mechanical trauma

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.

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.

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)

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)

tearing away of muscle or soft tissue (ex – hand being torn off)

wound from knife

Able to distinguish between entrance/exit wound by the shape and by the presence or absence of powder

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)

Hematopoietic syndrome (200-500 rads)
Gastrointestinal syndrome (500-1000 rads)
Cerebral syndrome (>2500 rads)

(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)

(500-1000 rads) caused by exposure to more than moderate level of radiation Causes ulceration of --- mucosa leading to diarrhea and bleeding

(>2500 rads) caused by over exposure to radiation (brain damage and death)

what sun burn is caused by

(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

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)

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)

partial thickness burn

Blisters caused by heat

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)

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

still has ability to perspire; normal or subnormal temperature; moist clammy ski

lost ability to perspire; very high body temperature; dry hot skin

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

low pressure to high pressure; visa versa (includes blast injuries from fireworks)

side effects involved with ingesting drugs/chemicals (prescription and illicit)

infections with microorganisms

obesity; vitamin/protein deficiency

type of Immunological injury

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

These are needed for what?
A. Production of energy
B. Synthesis of protein
C. Maintenance of structure
Ability to replicate

steady state can be changed by these? (3)

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

literally means no nutrition
caused by hormonal changes
Muscular dystrophy is this in muscle

Hypertrophy signs

look of hyperplastic follicles

A. undergrowth
1. not an adaptation, it is a developmental failure to develop to adult size
------ kidney doesn’t function properly

A. no growth
1. Developmental: failure to develop

Replacement of (columnar) epithelium of airways with squamous epithelium (squamous metaplasia)

irreversible change in tissue

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”

Cells can express injury by accumulations of different kinds of material in the cytoplasm. This can result from:

cloudy swelling (----- in the cytoplasm)
1. ----- vacuoles pushing the nuclei to the side (hydropic change) (very reversible)

--- 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

looks similar to other accumulations, differentiate using glycogen stain

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

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

hyaline membrane disease

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

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

a pigment (brown black pigment) that is produced by melanocytes
You can see accumulation of ------ on the skin

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

What color does hemosiderin stain

hemosiderin can accumulate where?

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

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.

Cytoplasmic changes

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

nucleus gets smaller

nucleus gets smaller and breaks up

nucleus disappears

Complications of Thrombosis that leads to sudden hypoxia and subsequent necrosis
1. Due to coagulation necrosis (except in brain-liquifactive necrosis)

Things to consider about an infarction

main vessel is occluded
results in prominent boundary line b/w necrotic and viable part of effected organ

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)

Two vessels that slight branch and supply blood to one areaAlso get Hemorrhagic Infarct here

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

Usually hemorrhagic infarctsDue to statsis or Thrombosis in vein

Can arise during obstretic emergencies, malignancies, sepsis, major trama

Steps of the Extrinsic and Intrinsic coagulation pathways that are activated at the microvascular level unnecessarily in Disseminated Intravascular Coagulation (DIC)

Extrinsic and Intrinsic coagulation pathways are activated at the microvascular level unnecessarily.
Billions of microvasculature are occluded with this problem

Lab test results for DIC

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…

2 types of Embolization

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

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

What's worse? one small venous embolus or shower of emboli

1. Can lead to dyspnea, anginal pain, syncope, venous distention of neck.

can lead to the above plus sudden tachycardia and hyperventilation

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.

1. Hemorraghic coagulation necrosis ensues
2. Pleural effusion is also possible

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.

body is made up of how much water

Body is how much water in Extracellular

Body is how much water in Intravascular (blood vessels)

Body is how much water in Interstitial (Outside cells in ground substance of tissues)

Body is how much water in Intracellular

Localized accumulation of water

Body wide edema

Outside of the blood vessels

Forces acting on exchange between vasculature and interstitium

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

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)

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)

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

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

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?

Carries off the extra fluid left on the interstitial side

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.