Exam I Flashcards by Lexi DeVries

reversible functional and structural changes of cells in response to changes in their environment

adaptations

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increase in the size of cells

hypertrophy

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hypertrophy occurs in ___ cells

nondividing

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physiologic hypertrophy: normal ____ or ____ function

organization
enhanced

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hypertrophy in response to increased functional demand describes (weight lifter)

physiologic hypertrophy

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hypertrophy of uterine smooth muscle during pregnancy describes

physiologic hypertrophy

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in pregnancy, ____ stimulation causes smooth muscle cells to increase in size

estrogen

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pathologic hypertrophy is seen with up-regulation of (3)

fetal genes
fibrosis
dysfunction

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hypertension and cardiac valve disease (AORTIC STENOSIS) cause pressure overload which leads to

pathologic hypertrophy of cardiac muscle

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systolic murmur indicates

left ventricular hypertrophy

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aortic stenosis causes

left ventricular hypertrophy

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boxcar nuclei in cardiac muscles indicates

left ventricular hypertrophy

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increase in the number of cells

hyperplasia

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hyperplasia is the result of
(2)

growth factor driven proliferation of mature cells
OR
decrease in cell death

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hyperplasia occurs in ___ cells

dividing

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physiologic hyperplasia is d/t the action of

hormones or growth factors

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increased functional demand of lactate glands results in

physiologic hyperplasia

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low ambient oxygen tension at high altitude results in bone marrow

compensatory erythroid hyperplasia (physiologic)

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certain viral infections like HPV are cause what characteristic response

pathologic hyperplasia

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most forms of pathologic hyperplasia are caused by excessive or inappropriate actions of

hormones or growth factors on target cells

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an enlarged prostate is an example of

benign prostatic hyperplasia

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endometrial hyperplasia is a response to

unopposed estrogen

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pathologic hyperplasia elevates the risk of acquiring genetic alterations that drive

unregulated proliferation and cancer

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pathologic hyperplasia is often associated with increased risk of

cancer

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stepwise progression from normal to cancer

normal hyperplasia dysplasia cancer

reduction in size of an organ or tissue d/t decrease in cell size and/or number

atrophy

____ is common during normal development

physiologic atrophy

atrophy of the endometrium from premenopausal to postmenopausal is an example of atrophy d/t...

loss of hormonal stimultion

disuse atrophy: immobilized limbs can cause... (3)

1 loss of proteoglycans in articular cartilage 2 decreased strength of ligaments 3 osteopenia

loss of innervation can cause

denervation atrophy

decreased blood supply, such as renal artery stenosis, can cause

atrophy

profound protein calorie malnutrition

Marasmus

what is an example of atrophy from pressure

Rathke Cleft Cyst causes hypopituitary

atrophy results in decreased _____ and increased ____

protein synthesis protein degradation

what are the two mechanisms of atrophy

1. ubiquitin protease pathway 2. autophagy

cell eats its own contents

autophagy

what molecule does autophagy use

LC3

_____ plays a role in cancer, neurodegenerative disorders, infectious diseases, and inflammatory bowel diseases

autophagy

adrenal gland atrophy can be caused by

exogenous corticosteroids

adrenal gland hyperplasia can be caused by

pituitary adenoma

menstrual cycle: atrophy occurs during

menstrual phase

menstrual cycle: hyperplasia occurs during

proliferative phase

menstrual cycle: hypertrophy occurs during

secretory phase

change in which one differentiated cell type is replaced by another cell type

metaplasia

metaplasia is the result of

reprogramming of normal local tissue stem cells in response to a potentially injurious stimulus

metaplasia can be d/t colonization of differentiated cell populations from

adjacent sites

metaplasia is often associated with increased risk of

cancer

the cancer is typically the same histologic cell type as the

metaplasia

what is the most commonly used example of metaplasia

squamous metaplasia

chronic inflammation and vitamin A deficiency can cause

squamous metaplasia

most common epithelial metaplasia is _____ and is usually d/t ______

columnar to squamous chronic inflammation

cervical cancer occurs at the ____ which is what cell type

transformation zone squamocolumnar junction

what type of cancer occurs at the transformation zone of the cervix

squamous cell carcinoma

____ metaplasia occurs in the esophagus near the esophageal sphincter

glandular

what is the cancer risk of glandular metaplasia of the esophagus

adenocarcinoma

formation of cartilage, bone, or adipose cells in tissues that normally do not contain these elements

connective tissue metaplasia

is connective tissue metaplasia associated with cancer risks?

NO!

disordered growth

dysplasia

dysplasia is a ____ change

premalignant

4 mechanisms lead to intracellular accumulations: 1. 2. 3. 4.

1. inadequate removal of normal substance secondary to abnormal metabolism 2. accumulation of an endogenous substance secondary to genetic or acquired defects 3. failure to degrade metabolite secondary to inherited enzyme deficiencies 4. deposition and accumulation of exogenous substance

abnormal accumulation of triglycerides within parenchymal cells

steatosis

steatosis is most commonly seen in

liver

in high income nations, steatosis is usually d/t

ethanol nonalcoholic fatty liver disease

intracellular accumulations of cholesterol can cause

atherosclerosis

intimal macrophages and intimal smooth muscle cells are filled with lipid vacuoles

intracellular cholesterol

multiple small vacuoles

foam cells

atherosclerosis (cholesterol intracellular)

if cells rupture, they spill extracellular cholesterol

cholesterol clefts (long needle shaped crystals)

intracellular accumulation of lipid, usually cholesterol, within macrophages

hyperlipidemia

clusters of foam cells in the skin and tendons

xanthomas

cholesterol-laden macrophages in the lamina propria of the gallbladder

cholesterolosis

strawberry gallbladder

cholesterolosis

Niemann-Pick Disease, Type C

enzyme mutation that causes cholesterol accumulation in multiple organs

normal secreted protein in excessive amounts

Russel Bodies - Plasma Cells

Russel Bodies causes increased synthesis of

Immunoglobulins

what normally inhibits neutrophil elastase

alpha-1 antitrypsin

alpha 1 antitrypsin deficiency causes misfolded protein to

accumulate in hepatocyte cytoplasm and is not secreted

alpha 1 antitrypsin deficiency causes - lungs: - liver:

lungs: emphysema from lack of PRO enzymatic activity liver: death from protein accumulation

what should you consider in a young person with liver and lung disease

alpha 1 antitrypsin deficiency

eosinophilic cytoplasmic inclusions composed predominantly of cytokeratin intermediate filaments

alcoholic hyalin

neurofilaments in Alzheimers disease

neurofibrillary tangle

homogeneous, glassy, amorphous, pink appearance on H&E

hyaline

increased intracellular glycogen can be seen with abnormality in

glucose or glycogen metabolism

positive PAS stain indicates

increased glycogen intracellularly

disease involving increased glycogen intracellularly in the heart

Pompe Disease (glycogen storage disease type II)

Von Gierke Disease

Liver glycogen storage disease type I

most common exogenous pigment in cells is

carbon (coal dust) (Anthracosis)

purple line on gums, hemolytic anemia, basophilic stippling of RBC

Lead Poisoning

golden-brown lipid/protein complexes secondary to lipid peroxidation (WEAR and TEAR pigment)

Lipofuscin (in heart)

tumor composed of malanocytes

malignant melanoma

hemosiderin

iron

hemoglobin derived granular yellow-brown pigment

hemosiderin

the two major storage forms of iron

ferritin hemosiderin

incompletely degraded aggregates of ferritin and other subcellular constituents

hemosiderin

hemosiderin in the lung indicates

left-sided heart failure

what stain confirms iron

Prussian Blue

Wilson's disease

endogenous copper in brain, liver, and cornea

rings on the cornea in Wilson's Disease

Kayser-Fleischer rings

bilirubin encephalopathy

kernicterus

calcium deposition in damaged tissue or areas of necrosis

dystrophic calcification

which calcification tends to be localized and normal serum Ca levels

dystrophihc

calcium deposition in normal tissue

metastatic calcification

which calcification tends to be widespread or diffuse and has increased serum Ca levels

metastatic

where is dystrophic calcification commonly seen

arteries (atherosclerosis) cardiac valves

concentric laminated calcifications seen most frequently in certain ovarian and thyroid cancers and meningiomas

Psammoma Bodies

where is metastatic calcification most commonly seen

gastric mucosa, lung, kidney (acid-secreting environments)

after a fixed number of divisions, cells become arrested in a terminally nondividing state called

replicative senescence

2 mechanisms underlying senescence

1. progressive shortening of telomeres 2. activation of tumor suppressor genes (p16)

premature aging and increased incidence of malignancies due to defective DNA helicase protein

Werner Syndrome

mutation in Lamin A protein leading to premature aging

Hutchinson-Guilford Progeria Syndrome

accumulation of misfolded proteins can trigger ____ and contribute to cellular aging

apoptosis

___ restriction increases cellular longevity

caloric

caloric restriction increases cellular longevity by

decreasing IGF-1 and insulin pathway

family of protein deacetylases

sirtuins

caloric restriction increases

sirtuins

if the limits of adaptive responses are exceeded or if cells are exposed to damaging insults, deprived of nutrients, or compromised by mutations leads to

cell injury

is cellular swelling reversible or irreversible

reversible

what is the earliest manifestation of all forms of cell injury

cellular swelling

is fragmentation of plasma membrane and organelles reversible or irreversible cell injury

irreversible

is mitochondrial damage (loss of ATP synthesis) reversible or irreversible cell injury

irreversible

are pyknosis, karyorrhexis, and karyolysis reversible or irreversible cell injury

irreversible

cellular swelling is d/t dysfunction of

plasma membrane sodium transport or Na/K ATPase

ischemia leads to ____

ATP depletion and then mitochondrial damage

what is produced in large amounts by leukocytes (neutrophils and macrophages) to kill microbial organisms

ROS

what are some antioxidants that inactivate/block free radicals

vitamins E and A ascorbic acid (vit C) glutathione

what serves as second messengers in signaling pathways

Calcium ions

ischemia and some toxins causes increased ____

cytosolic Ca and Ca influx across plasma membrane

3 major mechanisms of membrane damage

1 hypoxia/ATP depletion 2 ROS 3 increased intracellular Ca

plasma membrane damage causes

leakage of intracellular contents into extracellular space (including bloodstream)

elevated LDH indicates

cell injury

elevated GGT, AST, and ALT indicate

hepatocyte injury

elevated alk phos indicates

biliary obstruction

elevated creatine kinase and myoglobin indicates

cardiac or skeletal muscle injury

troponin I and T isoenzymes evaluate

myocardial cells

lipase and amylase levels evaluate

pancreas

hemoglobin levels evaluates

RBC hemolysis

deficiency of O2 in blood tissue

hypoxia

deficiency of O2 in blood

hypoxemia

diminished blood supply to any tissue or organ of the body causing a shortage of oxygen

ischemia

describe ischemia-reperfusion injury

restoration of blood flow may cause exacerbation of reversible cell injury which may lead to irreversible lethal cell injury

ischemia followed by restoration of blood flow can lead to... (2)

recovery ischemia-reperfusion injury

increased production of ROS, activation of complement, increased cytokines, increased Ca can all cause what injury?

Ischemia-Reperfusion Injury

cyanid poisons/attacks...

mitochondrial cytochrome oxidase

___ was once widely used in dry cleaning and is converted to a ROS by P-450

CCl4

analgesic drug converted to toxic product during detoxification in the liver, leading to cell injury

acetaminophen (Tylenol)

what are the two principal types of cell death

necrosis apoptosis

mitochondrial damage, Ca, and membrane damage can lead to

necrosis

protein misfolding, DNA damage can lead to

apoptosis

necrosis vs. apoptosis: cell size

necrosis: enlarged apoptosis: reduced (shrinks)

necrosis vs. apoptosis: plasma membrane

necrosis: disrupted apoptosis: intact

necrosis vs. apoptosis: adjacent inflammation

necrosis: frequent apoptosis: none

is necrosis pathologic of physiologic

pathologic

is apoptosis pathologic or physiologic

usually physiologic

what type of necrosis is usually caused by ischemia?

coagulative necrosis

describe coagulative necrosis Cause: texture: tissue architecture: color on H&E: cell outline: inflammation?

ischemia firm preserved architecture eosinophilic (pink) preserved cell outline slight inflammatory infiltrate

loss of ___ is seen in coagulative necrosis

nuclei

what is the sequence of nuclear changes in coagulative necrosis?

pyknosis karyorrhexis karyolysis

nuclei are condensed and dense

pyknosis

nuclei break into fragments

karyorrhexis

nuclei are dissolved

karyolysis

what type of necrosis is seen in MIs

coagulative necrosis

what type of necrosis is d/t bacteria/fungi/amoeba infection

liquefactive

lung abscess is an example of what kind of necrosis

liquefactive

neutrophils + necrotic material =

pus

infarction / ischemia of the BRAIN tissue leads to

liquefactive necrosis

digestion of dead cells so tissue turns into a viscous liquid describes

liquefactive necrosis

necrosis involving a limb

gangrenous necrosis

term for tissue necrosis with putrefaction

gangrene

necrosis involving the GI tract

gangrenous necrosis

ischemic coagulative necrosis of a limb

DRY gangrenous necrosis

liquefactive necrosis from superimposed bacterial infection PLUS coagulative necrosis of a limb

WET gangrene / gangrenous necrosis

gas gangrene is often caused by

anaerobic Clostridia

myonecrosis and gas formation

gas gangrene

necrosis resulting in cheese-like debri

caseous necrosis

what commonly causes caseous necrosis

TB fungi Nocardia

describe caseous necrosis: cell outline: liquefied? inflammation?

loss of cell outline not liquefied GRANULOMATOUS inflammation

granulomatous inflammation = ___ + ____

mononuclear cells (lymphs and macrophages) multinucleated giant cells

acute pancreatitis can cause

fat necrosis

what is saponification

free fatty acids from fat necrosis combine with Ca to form chalky white areas

is fat necrosis secondary to trauma seen with saponification?

no (nonenzymatic)

what type of necrosis is usually seen in blood vessels

fibrinoid

the amorphous pink material seen in fibrinoid necrosis resembles

fibrin

immune mediated vasculitis (polyarteritis nodosa) can lead to

fibrinoid necrosis

what type of necrosis can be seen in aging and severe HTN

fibrinoid

programmed cell death

apoptosis

what process is used in embryogenesis

physiologic apoptosis

death by ___ is a normal phenomenon used to eliminate cells that are no longer needed or maintain a constant # of cell populations in tissues

apoptosis

activation of p53 causes

cell cycle arrest to repair DNA

if DNA damage is extensive (beyond repair) then p53 initiates

apoptosis

describe how viral infections cause apoptosis

granzyme enters cell through perforin channel --> apoptosis

activation and cascade of caspase enzymes is central process in apoptosis - C: - Asp:

cysteine: enzyme activation site aspartic acid: cleavage site on target pros

____ activation is universal feature of apoptosis

caspase

which pathway is responsible for most physiologic and pathologic apoptosis?

mitochondrial (Intrinsic) pathway

____ inhibits the intrinsic pathway of apoptosis

BCL2

what happens if BCL2 is overexpressed?

cells proliferate uncontrolled (BCL2 is anti-apoptotic)

BAX and BAK are (pro or anti)-apoptotic

PROapoptotic!

removing apoptotic cells: ____ engulf apoptotic bodies with no significant inflammation

macrophages

loss of p53 can lead to

cancer

excessive apoptosis can lead to

neurodegenerative diseases

insufficient apoptosis can lead to (2)

autoimmunity cancer

hybrid form of cell death with features of both necrosis and apoptosis

necroptosis

necroptosis is ___-independent

caspase

in necroptosis, ___ is not activated

caspase 8

where do we see physiologic necroptosis

bone growth plate development

pyroptosis is a form of apoptosis with release of

fever inducing cytokine IL-1

programmed cell death accompanied by fever

pyroptosis

historically, what is the purpose of inflammation?

bring phagocytic cells to the injured area to engulf invading bacteria

what is the inflammation reaction sequence? (5)

Recognition Recruitment Removal Regulate Repair

how are microbial components or substances released from damaged cells recognized

DAMPs and PAMPs

PAMPs and DAMPs are recognized by

TLRs

cytosol proteins that recognize ATP, dsDNA, PAMPs, and DAMPs

NLRs

primary cell of acute inflammation

neutrophils

what cells regulates vascular dilation and contraction and mediate leukocyte recruitment?

endothelial cells

what cells regulate both acute and chronic inflammation

monocyte/macrophage

what are the four cardinal signs of inflammation?

pain (dolor) heat (calor) redness (rubor) swelling (tumor)

what are the most common and medically important causes of inflammation

infections

infections are recognized via ____ and tissue necrosis is recognized via ____

PAMPs DAMPs

____ on vascular smooth muscle is the earliest manifestation of acute inflammation

histamine

what are the 3 major components of acute inflammation

1 vasodilation --> increased blood flow 2 increased permeability 3 emigration of leukocytes from microcirculation

histamine on vascular smooth muscle causes

vasodilation

the escape of fluid, proteins, and blood cells from the vascular system to the interstitial tissue or body cavities

exudation

what is the most common mechanism of vascular leakage

contraction of endothelial cells

what mediators increase vascular permeability (3) in acute inflammation

histamine NO prostaglandins

extravascular fluid that has a high protein concentration and contains cellular debris

exudate

exudate implies...

existence of an inflammatory process and increased vascular permeability

fluid with low protein content and little/no cellular material

transudate

trasudate etiology is not

inflammatory

transudate is a result of

osmotic or hydrostatic imbalances

CHF leading to b/l pleural effusions is an example of

transudate effusions

cirrhosis leading to ascites fluid is an example of

transudate effusions

excess of fluid in the interstitial space or body cavity

edema

is edema an exudate or tranudate?

can be EITHER!

inflammatory exudate rich in leukocytes, dead cell debris, occasionally microbes

purulent exudate (pus)

purulent exudate is rich in

neutrophils

types of inflammatory exudate: skin blisters

serous

types of inflammatory exudate: adhesions following surgery

fibrinous

types of inflammatory exudate: cloudy mucus (runny nose)

catarrhal

types of inflammatory exudate: abscesses, boils, cellulitis

purulent

types of inflammatory exudate: hematoma

hemorrhagic

inflamed lymph nodes are often enlarged d/t ___ of the lymphoid follicles and increased number of ____ and _____

hyperplasia lymphocytes and macrophages

presence of ____ near a skin wound is a telltale sign of an infection in the wound

red streaks

presence of red streaks is diagnostic of ___ and may be accompained by

lymphangitis painful enlargement of the draining lymph nodes (lymphadenitis)

inflammation of lymph vessels

lymphangitis

inflammation of lymphh nodes

lymphadenitis

what two things assist in leukocyte margination and rolling

E-selectin P-selectin

____ on leukocytes interact with ____ on endothelial cells during leukocyte migration

integrins adhesion molecules

____ are involved in INITIAL leukocyte rolling

selectins

____ are involved in firm adhesion of leukocytes

integrins

migration of leukocytes through intact endothelium

transmigration or diapedesis

after exiting circulation, leukocytes move in the issues toward the side of injury by a process called

chemotaxis

what are 3 important chemoattractants for neutrophils and monocytes during acute inflammation?

C5a Leukotriene B4 fMLF

in pseudomonas bacterial infections, ___ are CONTINUOUSLY recruited for several days

neutrophils

in viral infections, ___ may be the first to arrive

lymphocytes

main cell type of hemlinthic infections and allergic reactions

eosinophils

leukocytes leaving the vasculature and migrating to the site of bacterial inoculation is mediated by

chemokines

the two major phagocytes are

neutrophils macrophages

killing of microbes by phagocytes is accomplished by

ROS RNS lysosomal enzymes

efficiency of phagocytosis is more efficient when microbes are coated with

opsonins

inherited deficiencies of components of phagocyte oxidase causes

chronic granulomatous disease

mutation of lysosomal trafficking regulator protein that leads to decreased phagocytosis

Chediak Higashi Syndrome

pts with Chediak Higashi Syndrome are at risk of recurrent...

pyogenic infections and oculocutaneous albinism

inherited defect of phagocytes resulting in impaired microbial killing

myeloperoxidase deficiency

myeloperoxidase deficiency is asymptomatic unless

diabetic (recurrent severe Candida infections)

extracellular fibrillar networks that trap microbes and prevent their spread

Neutrophil Extracellular Traps (NETs)

in some infections that are difficult to eradicate (TB and some viruses), the prolonged host response contributes more to the pathology than the microbe does itself describes what?

leukocyte-mediated tissue injury

terminating the acute inflammatory response: as pathogens are cleared, levels of ____ and ___ markedly decrease --> no triggering of innate immune cells

inflammatory cytokines (IL-1) tumor necrosis factor (TNF)

terminating the acute inflammatory response: increase in anti-inflammatory molecules such as...

IL-1 ANTAGonist TGF-beta IL-10

cell-derived mediators of inflammation are sequestered in

intracellular granules

plasma-derived mediators of inflammation are produced by ___ and must be ___

the liver activated

describe the role of histamine in inflammation

vasoactive amine that causes vasodilation and increases permeability of venules by producitng interendothelial gaps in venules

histamine is released by

mast cell degranulation

what increases vascular permeability and causes contraction of smooth muscle, dilation of blood vessels, and pain

bradykinin

bradykinin is a mediator in some forms of...

allergic reaction such as anaphylaxis

what is secreted by sensory nerves and various leukocytes and is involved in transmission of pain signals and increasing vascular permeability

substance P

prostaglandins and leukotrienes are produced from _____ and stimulate...

arachidonic acid vascular and cellular reactions in acute inflammation

prostaglandins are generated by the actions of two ____ called...

cyclooxgenases COX-1 and COX-2

what are generated from AA and suppress inflammation by inhibiting neutrophil chemotaxis and adhesion to endothelium

lipoxins

how do lipoxins suppress inflammation?

inhibit neutrophihl chemotaxis and adhesion

aspirin, ibuprofen, and other NSAIDs are ____

cyclooxygenase inhibitors

pharmacologic agents that inhibit leukotriene production are useful in tx of

asthma

leukotriene receptor ANTAGonists are useful in tx of

asthma

family of proteins that act as chemoattractants for specific types of leukocytes

chemokines

what do TNF and IL-1 play an important role in?

leukocyte recruitment by promoting adhesion and migration

TNF alpha acts on the liver leading to production of

actue phase proteins (acute phase response)

TNF acts on the hypothalamus leading to

fever

TNF acts on muscle and fat cells leading to

increased catabolism cachexia

acute phase response consists of (3)

fever increased acute-phase proteins (CRP and fibrinogen) leukocytosis

what is produced by the liver and is a clinical sign of inflammation

C-reactive protein (CRP)

what is correlated with TNF and indicates inflammation

erythrocyte sedimentation rate (ESR)

IL-1 is produced mostly by activated

macrophages

what is a mediator of acute inflammatory response, specifically playing a major role in induction of fever

IL-1

IL-1 is a potent ____ cytokine, meaning it suppresses ____

anorexic appetite

TNF antagonists have been remarkably effective in the tx of

chronic inflammatory diseases (RA, psoriasis, IBD)

the critical step in complement activation is the...

proteolysis of C3

the lectin complement pathway involves mannose-binding lectin binding to carbs on microbes and directly activating

all three complement pathways lead to formation of

active C3 converstase

function of active C3 convertase

spilts C3 into two functionally distinct fragments (C3a and C3b)

what complement cleavage products stimulate histamine release from mast cells leading to vasodilation and increased permeability

C3a C5a

C3a and C5a are considered

anaphylatoxins

4 clinical features of anaphylaxis

hypotension bronchospasm airway obstruction hives/urticaria

tx for anaphylaxis

intramuscular epinephrine (adrenaline)

what is the function of C3b

acts as opsonins and promotes phagocytosis by neutrophils and macrophages

complement proteins form a ring in the plasma membrane of target cell causing cytolysis

membrane attack complex (MAC)

deposition of MAC results in...

increased permeability to water and ions resulting in lysis

deficiency of the complement components of MAC predisposes pts to

Neisseria infections

what is the first complement protein of the classical pathway

inherited deficiency of C1 inhibitor causes

hereditary angioedema

DAF prevents...

formation of C3 convertases

CD59 inhibits...

formation of MAC

acquired deficiency of enzyme that creates GPI anchors leads to...

deficiency of complement regulators and excessive complement activation and lysis of RBC = Paroxysmal Nocturnal Hemoglobinuria (PNH)

deficiency of complement regulators and excessive complement activation leads to

Paroxysmal Noctural Hemoglobinuria (PNH)

____ inflammation is marked by the exudation of cell-poor fluid into body spaces or cavities

serous

accumulation of fluid into a cavity from the plasma (as a result of increased permeability) or from secretion of mesothelial cells

effusion

describe fibrinous inflammation

with increased vascular permeability, large molecules such has fibrinogen pass out of the blood and fibrin is formed and deposited in the extracellular space

a fibrinous exudate is characteristic of inflammation in the

lining of body cavities such has meninges, pericardium, and pleura

pericardial effusions are often ___ exudates associated with...

fibrinous pericardial murmur-- a friction rub sound (PERICARDIAL RUB)

____ inflammation is characterized by the production of pus, an exudate consisting of neutrofils, liquefied debris of necrotic cells, and edema fluid

purulent

___ are localized collections of pus

abscesses

___ are produced by the shedding of inflamed necrotic tissue

ulcers

what is "resolution" of acute inflammation?

restoration of the site to normal

resolution is typically the outcome of acute inflammation when the injury is...

limted or short-lived has had little tissue destruction damaged parenchymal cells can regenerate

what occurs after substantial tissue destruction, injury involves tissues that can't regenerate, or when there is abundant fibrin exudation that can't be cleared

healing by CT replacement (scarring, fibrosis)

what occurs when the acute inflammatory response cannot be resolved

chronic inflammation

redness, warmth, and swelling during acute inflammation are caused by

increased blood flow and edema

what produce histamine, TNF, IL-1, IL-6, and chemokines at the sites of infection of injury

Sentinel Cells

the products from sentinel cells lead to... (4)

increase vascular permeability increase adhesion molecules leukocyte migration phagocytosis

prolonged process in which inflammation, tissue injury, and attempts to repair are all active at once

chronic inflammation

persistent infections by microbes such as ____ can evoke an immune reaction called _____

mycobacteria, viruses, fungi, and parasites delayed-type hypersensitivity

what is a systemic immune mediated chronic inflammatory disease mainly targeting synovial tissue

RA most commonly causes tissue injury in the

hands and wrists

in chronic inflammation, attempts at healing by CT replacement of damaged tissue is accomplished by ___ and ___

angiogenesis fibrosis

what cells mediate chronic inflammation? (6)

monos/macros lymphocytes plasma cells dendritic cells fibroblasts eosinophils

eosinophils are abundant in... (2)

IgE mediated inflammation parasitic infections

the dominant cells in most chronic inflammatory reactions are

macrophages

macrophages activate other cells, most notably...

T lymphocytes

macrophages in the liver are called

Kupffer cells

macrophages in the spleen and lymph nodes are called

sinus histiocytes

macrophages in the nervous system are called

microglial cells

macrophages in the lungs are called

alveolar macrophages

macrophages in the bone are called

osteoclasts

macrophages in the skin are called

Langerhans cells

the macrophages throughout the body comprise the

mononuclear phagocyte system

macrophages display Ag to and recieve signals from ___

T lymphocytes

what are the two major pathways of macrophage activation?

classical alternative

classical macrophage activation may be induced by... (3)

microbial products Th1 cells secreting IFN-gamma foreign substances including crystals/particulate

classically activated macrophages are called

M1 macrophages produce... and upregulate...

NO and ROS lysosomal enzymes

alternative macrophage activation is induced by... (2) produced by ____

IL-4 and IL-13 Th2 cells

principal function of M2 macrophages is

tissue repair

M2 macrophages secrete growth factors that promote... (3)

angiogenesis activate fibroblasts stimulate collagen synthesis

function of IFN-gamma

activate macrophage

prolonged reactions involving T-cells and macrophages can lead to the formation of

granuloma

what chemical mediator is most important in granuloma formation

IFN-gamma

eosinophils have granules that contain ____which is toxic to parasites but also lysis of epithelial cells

major basic protein

what is the pro and con of eosinophils

they control parasitic infections also cause lysis of mammalian epithelial cells

mast cells express FcERI that binds

the Fc portion of the IgE Ab

in immediate hypersensitivity reactions IgE binds to the Fc receptor leading to...

degranulation of histamine and prostaglandins

what response occurs during allergic reactions to food, insect venom, or drugs (sometimes anaphylactic shock)

mast cell degranulation d/t IgE bindding to Fc receptor

basophils are ___ and have receptors for ___ which can trigger release of histamine

phagocytic IgE

basophils are the predominant source of

IL-4 IL-13

in chronic bacterial infection of bone (___), a ___ exudate can persist

osteomyelitis neutropihlic

there are no ____ in portal chronic inflammation

neutrophils

form of chronic inflammation characterized by collections activated macros, T-cells, and sometimes associated with central necrosis

Granulomatous inflammation

what type of granuloma occurs in the absence of T-cell mediated immune responses

foreign body granuloma

when FB granulomas form around materials such as TALC (associated with IV drug use), sutures, or other fibers are large enough to

preclude phagocytosis by a macrophage and don't elicit any specific inflammatory response

a FB can be identified in the center of the granuloma if viewed with

polarized light

which type of granuloma is caused by a variety of agents that are capable of inducing a persistent T-cell mediated immune response

immune granulomas

what kind of granuloma do mycobacteria TB and fungal organisms infections cause?

caseating granuloma (necrotizing)

what kind of granuloma do sarcoid, Crohn disease, and leprosy cause?

Non-caseating granuloma (non-necrotizing)

inflammation is associated with cytokine-induced systemic reactions that are collectively called

acute-phase response

what cytokines are important mediators of the acute-phase reaction

TNF IL-1 IL-6

substances that induce fever are called

pyrogens

increase in body temp is caused by ___ that are produced in the hypothalamus

prostaglandins

elevated acute-phase proteins are mostly synthesized in the

liver

three acute-phase proteins are

CRP fibrinogen serum amyloid A (SAA)

CRP and SAA bind to microbial cells walls and act as

opsonins and fix complement

elevated serum levels of CRP have been preposed as a marker for increased risk of

MI in pts with coronary artery disease

___ bind to red cells and causes them to form stacks

fibrinogen

increased inflammation sedimentation rate indicates

inflammation!

increased thrombopoietin results in

thrombocytosis (increased platelet count)

most bacterial infections induce

neutrophilia

viral infections cause

lymphocytosis (increase in # of lymphocytes)

allergies and parasitic infections cause

eosinophilia (increase in # of eosinophils)

typhoid fever and infections by some viruses, rickettsiae, and certain protozoa are associated withh

leukopenia (decreased circulating white cells)

___ and ___ are important in givign the signs and symptoms of infection/inflammation

IL-1 TNF

the major microscopic abnormalities of Alzheimers are

neuritic (senile) plaques neurofibrillary tangles

____ in the brain drives progression from the presence of amyloid plaque and tau tangles to onset of dementia and Alzheimers

inflammation

chronic hepatitis C infection of the liver is associated with

hepatocellular carcinoma

chronic H. pylori gastritis is associated with

gastric carcinoma

inflammatory bowel disease (UC and Crohn's) are associated with

colon carcinoma

repair of damaged tissue occurs by two processes:

regeneration scarring

restoration of normal cells

regeneration

deposition of CT

scarring

what are the 3 tissue groups based on proliferation capacity

labile stable permanent

continuously dividing tissues

labile tissues

tissues continuously being lost and replaced by maturation from tissue stem cells and by proliferation of mature cells

labile tissue

surface epithelia and hematopoietic cells in bone marrow are examples of

labile cells

cells with only minimal proliferative activity normally, however they are capable of dividing in response to loss of tissue mass

stable tissues

parenchyma of most solid tissue (liver, kidney, and pancreas), endothelial cells, smooth mm. are examples of what cells

stable tissues

terminally differentiated and nonproliferative cells

permanent tissues

neurons and cardiac muscle cells are examples of what cell type

permanent tissues

the most important source of growth factors in cell proliferation are

macrophages

in cell proliferation, all growth factors activate signaling pathways that stimulate

DNA replication and biosynthesis of other cell components

which organ has remarkable capacity to regenerate

liver

liver regeneration occurs by 2 major mechanisms:

proliferation of remaining hepatocytes repopulation from progenitor cells

what occurs during the priming phase of liver regeneration?

cytokines (IL-6) are produced by Kupffer cells to make liver cells ready to respond to growth factors

what happens in the growth factor phase of liver regeneration?

growth factors such has HGF and TGF alpha stimulate hepatocyte metabolism and entry of cells into the cell cycle

in chronic liver injuries or inflammation, what cells contribute to repopulation?

progenitor cells

what are the 4 steps of scar formation

inflammation cell proliferation formation of granulation tissue deposition of CT

in scar formation, endothelial cells and pericytes begin

angiogenesis

in scar formation, ____ proliferate and lay down collagen fibers

fibroblasts

what is the growth factor that drives angiogenesis in scar formation and increases vascular permeability

VEGF

VEGF increasing vascular permeability accounts for ___ in healing wounds

edema

granulation tissue in scar formation consists of (4)

proliferation of fibroblasts deposition of CT new formed vessels leukocytes

in scar formation, granulation tissue is progressively replaced by

collagen/CT

during wound healing, maturation and reorganization of CT produces the

stable, fibrous scar

the laying down of CT in scar formation occurs in two steps:

migration and proliferation of fibroblasts into site of injury deposition of ECM proteins produced by these cells

what is the most important cytokine for the synthesis and deposition of CT during scar formation

TGF-beta

what stimulates fibroblast migration and proliferation and decreases ECM degradation during scar formation

TGF-beta

what is involved in fibrosis of lungs, liver, and kidneys. inresponse to chronic inflammation

TGF-beta

the degradation of collagens and other ECM components is accomplished by a family of

matrix metalloproteinases (MMPs)

a ___ deficiency leads to delayed wound healing

zinc

what two deficiencies inhibit collagen synthesis and retards wound healing?

protein vitamin C

what drugs cause slow wound healing (4)

immunosuppressive agents corticosteroids NSAIDs anticoagulants

how do glucocorticoids affects wound healing

result in weakness of the scar d/t inhibition of TGF-beta production and diminished fibrosis/collagen synthesis

dehisce

pulling apart of wounds

arteriosclerosis and diabetes and varicose vv. impair healing because of

poor perfusion

inflammation arising. intissue spaces develops extensive

exudates

an injury will heal via first intention when...

it involves only the epithelial layer

first intention: by day 3, neutrophils are replaced by

macrophages

first intention: by day 5, ____ reaches its peak

neovascularization

first intention: during the second week, there is continued...

collagen accumulation and fibroblast proliferation

an injury will heal via second intention when...

cell or tissue loss is more extensive (abscesses, ulceration, ischemic necrosis

in large wounds, there is a greater volume of ____ and therefore a greater mass of ____

granulation tissue scar tissue

second intention healing: at 2 weeks, provisional matrix is replaced by ____

Type I collagen

wound ___ is important in healing by secondary union because it decreases the gap between its dermal edges

contraction

what is the important cell type in wound contraction

myofibroblasts

sutured wounds have __% of the strength of normal skin

70%

when sutures are removed, usually at 1 week, wound strength is __% of unwounded skin but increases over the next 4 weeks

10%

wound strength reaches approximately __-__% of normal by 3 months

70-80%

defects in wound healing: venous leg ulcers may develop in elderly people as a result of

chronic venous HTN (which may be caused by varicose vv. or CHF)

arterial ulcers develop in individuals with h

atherosclerosis of peripheral aa. especially associated with diabetes

surgical incision reopens internally or externally

wound dehiscence

wound dehiscence can be precipitated by

vomiting coughing

excessive TGF-beta has been associated with

keloids hypertrophic scars

scar that extends beyond the borders of original wound

keloid

keloids are an increase in

type I and III collagen

scar that is excessive but confined to borders of original wound

hypertrophic scar

hypertrophic scars are an increase in

type III collagen

formation of excessive amounts of granulation tissue, which protrudes above the level of the surrounding skin and blocks re-epithelialization

exuberant granulation

exaggeration of contraction in a wound leads to

contracture

where are contractures particularly prone

palms, wrists, soles, anterior thorax

contractures are commonly seen after

serious burns

function of vascular hydrostatic pressure

pushes water and salts into the extracellular space

function of plasma colloid oncotic pressure

pulls water and salts into intravascular space

3 ways that fluid balance is disrupted

alteration of vascular endothelium increased vascular hydrostatic pressure decreased plasma protein

abnormal fluid balance causes

edema

fluid accumulation in the body cavities

effusions

fluid accumulation in the tissues

edema

noninflammatory causes of edema / effusions (4)

CHF liver failure renal disease malnutrition

why does nephrotic syndrome cause edema?

losing protein through the kidneys --> decreased plasma protein --> decreased plasma colloid osmotic pressure --> edema

abdominal effusion is called

ascites

fluid withh low protein content

tranudate

fluid with high protein content

exudate

type of effusion in CHF and hypoalbuminemia

serous

serous fluid plus RBCs

serosanguinous

type of effusion in hemopericardium (aortic/cardiac rupture)

sanguinous

type of effusion in infection

purulent

type of effusion in lymphatic obstruction

chylous

milky white fluid from lipids

chylous

type of effusion associated with malignant cells

malignant (neoplastic)

what two things stem from increased blood volumes within tissues

hyperemeia congestion

ACTIVE process where arterial dilation lets more blood into an area

hyperemia

hyperemia: increased ____ blood delivery causes ___

oxygenated erythema

PASSIVE process of blockage and reduction of venous outflow

congestion

congestion- coloration: ___ hemoglobin

cyanotic (blue-red) deoxygenated

one leg larger / more swollen than the other insinuates

DVT

what is the master regulator of hemostasis

endothelial cell

6 steps of normal hemostasis

1. endothelial injury and vasoconstriction 2. primary hemostasis--platelet plug 3. secondary hemostasis--clot and fibrin deposition 4. clot stabilization 5. clot inhibition/cessation 6. clot dissolution: fibrinolysis

Virchow's Triat

hypercoagulability stasis endothelial injury

immediately after endothelial injury there is reflex ___

neurogenic vasoconstriction

what substance causes neurogenic vasoconstriction immediately after endothelial injury and who releases it

endothelin injured endothelial cells

what is exposed after endothelial injury and what is released

collagen Von Willebrand's Factor (vWF)

vWF on exposed collagen causes

platelet ADHESION

platelet adhesion is via what protein/receptor

PAR G-protein receptor GpIb

once the platelets are adhered, what causes platelet activation?

ADP

activated platelets then...

recruit more platelets

platelet aggregation occurs d/t what substance

thromboxane (TxA2)

what platelet receptor attaches to circulating fibrinogen

GpIIb/IIIa

what leads to irreversible platelet contraction via cytoskeleton changes

thrombin

the function of secondary hemostasis is to form a

clot/thrombus

during secondary hemostasis, tissue factor release binds ____ which kickstarts reactions that make

thrombin

reactions that make thrombin is called the

coagulation cascade

function of activated thrombin in secondary hemostasis

cleaves circulating fibrinogen into insoluble fibrin

during the coagulation cascade of secondary hemostasis, which factors are calcium dependent and require vit K as a cofactor?

II, VII, IX, X

what is special about factors II, VII, IX, and X?

Ca dependent require vit K cofactor

in vivo, tissue factor initiates the

clotting cascade

which pathway does PTT evaluate

intrinsic

which pathway does PT evaluate

extrinsic

what is factor II?

prothrombin

what is factor I?

fibrin

sequence of Ca-dependent coagulation factors

VIIa --> IXa --> Xa --> IIa

at which coagulation factor does the common pathway start at

which factors does PT evaluate

1, 2, 5, 7, 10

what factors does the PTT evaluate?

1, 2, 5, 8, 9, 10, 11, 12

PTT and PT BOTH evaluate which pathway

common pathway

what has a positive feedback loop on the clotting cascade?

thrombin

function of factor IIa

(thrombin) converts fibrinogen into cross linked fibrin

what factors does thrombin activate

XI, V, VII

intrinsic path is activated by factors in the

blood

extrinsic path is activated by

tissue factor

clot stabilization: fibrinogen is converted to

fibrin

clot stabilization: what contracts to form the permanent plug

fibrin platelet aggregation

clot stabilization: what is released by nearby healthy (uninjured) endothelial cells to limit the size of a clot

plasminogen activator thrombomodulin

what is released by endothelial cells to inhibit platelet function with clot cessation (3)

prostacyclin (PGl2) NO ADPase

function of prostacyclin (PGI2)

inhibits platelet aggregation

function of NO secreted by endothelial cells

inhibits adhesion and aggregation

function of ADPase in clot cessation

destroy ADP--inhibits aggregation

clot inhibition: what complex activates protein C

thrombomodulin, thrombin, and protein C

clot inhibition: activated protein C in the presence of protein S inhibits...

factor Va factor VIIIa

what activates antithrombin

haparan sulfate proteoglycans

antithrombin neutralizes... (3)

IIa IXa Xa

antithrombin's binding rxn is amplified by

heparin

how do you measure heparin activity

PTT

tissue factor pathway inhibitor on the endothelial cell surface (in the presence of protein S) inhibits... (2)

VIIa/TF complex Xa

in close dissolution (fibrinolysis), endothelial cells secrete

TPA

function of TPA

converts plasminogen to active plasmin

function of plasmin

breaks down fibrin

what inhibits plasmin

alpha2 plasmin inhibitor

plasminogen is also converted to plasmin by (besides TPA)

factor XII

factor XII deficiency causes a ___ state because it activates plasmin

hypercoaguable

what are 3 clinically administered plasminogen activators?

tPA, urokinase, streptokinase

a clot that has grown larger than required for its physiologic role as a hemostatic plug

thrombus

white thrombus

arterial thrombus

arterial thrombi cause ___ or ____

ischemia or infarction

red or stasis thrombi

venous thrombus

venous thrombi cause ____ and ____

vascular congestion and edema

embolism

dislodged thrombus that has traveled to other sites

describe Factor V Leiden

mutant factor V has decreased to activated protein C and is not deactivated

what should you consider in a pt with DVT, or recurrent pregnancy loss

Factor V leiden

what disease causes increased prothrombin levels and therefore increased thrombin?

Prothrombin G20210 A Mutation

Protein S Deficiency is a mutation in what gene?

PROS1

Protein C deficiency can occur with what 6 things?

hereditary deficiency vit K deficiency pregnancy liver/renal failure DIC Warfarin

what can happen when a pt with protein C deficiency is placed on warfarin

warfarin skin necrosis

Factor XII deficiency causes...

decreased plasmin activation and is prothrombotic (LOW plasmin means less fibrinolysis)

what is the etiology of Heparin-Induced Thrombocytopenia Syndrome (HIT) type II

heparin induces autoantibodies with Platelet factor 4

HIT, type II: autoantibody-heparin-platelet complexes activate platelets and cause

endothelial injury and a prothrombotic state

autoimmune disorder characterized by presence of one or more antiphosphlipid (aPL) autoantibodies

Antiphospholipid Ab Syndrome (APS)

autoimmune disorder characterized by venous or arterial thromboses, pregnancy complications (recurrent miscarriages, unexplained fetal death, premature birth

Antiphospholipid Ab Syndrome (APS)

how to detect antiphospholipid antibodies clinically (2)

lupus anticoagulant detected during a PTT false + serologic VDRL (syphyllis) test

thrombotic fragment that has moved through the venous or arterial system to a different site

thromboembolism

arterial emboli thhat lodge in systemic capillary beds causing ischemia and necrosis

systemic emboli

80% of systemic emboli originate from

intracardiac mural thrombi (often from L ventricular wall infarcts)

embolus from severe skeletal injuries/trauma

fat emboli

venous emboli lodge in pulmonary capillary bed causing SOB and possibly R sided heart failure

pulmonary emboli

venous embolism that ends up in systemic circulation causing tissue ischemia

paradoxical emboli

>95% of PEs are caused by

leg DVTs

sudden decreases in atmospheric pressure causes

gas embolism--decompression sickness

why does decompression sickness occur

nitrogen gas is dissolved in the blood and tissues at high pressure with ascent, nitrogen comes out of solution in the tissues and blood

what causes the bends in decompression sickness

rapid formation of gas bubbles within skeletal muscles

sudden drop in blood flow through the body

shock

hemorrhagic shock is an example of

hypovolemic shock

what is the most ocommon cause of septic shock

gram + bacteria

failure of myocardial pump can cause

cardiogenic shock

inadequate blood or plasma volume

hypovolemic shock

activation of cytokine cascades and peripheral vasodilation

ditributive shock

vitamin K deficiency can cause excessive bleeding because it decreases...

factors II, VII, IX, X proteins C and S

Bernard-Soulier Syndrome

Gp1b-IX deficiency

Glanzmann Thrombasthenia

GpIIb/IIIa dysfunction

Hemophilia A

factor VIII deficiency

Hemophilia B

factor IX deficiency

Hemophilia C

factor XI deficiency

liver diseases usually causes excessive bleeding d/t decreases in what

factors VII, IX, X, proteins C and S

umbilical cord stump bleeding

afibrinogenemia

males, umbilical cord stump bleeding, deep hematomas

Factor VIII deficiency

poor wound healing, severe scar formation

Factor XIII deficiency

oculocutaneous albinism, infections, neutrophihl peroxidase in clusions

Chediak-Higashi syndrome

mucocutaneous bleeding indicates an issue with

primary hemostasis / platelet disorder

petechiae and purpura indicate

platelet disorder

how to you dx Bernard-Soulier Syndrome

peripheral blood smear

no aggregation (flat line) with Ristocetin indicates...

Bernard Soulier Syndrome (GpIb deficiency) or vWF deficiency

no aggregation with epi, collagen, ADP, and AA indicates...

Glanzmann's Thrombasthenia (GpIIb/IIIa defciency)

what are two conditions that are defects in adhesion

vWF disease Bernard-Soulier Syndrome

NSAIDs and Aspirin inhibit

cyclooxygenase (TxA2 and PGs)

effect of NSAIDs and Aspirin

stops platelet aggregation

occasional spontaneous bleeding occurs with what platelet count

10-30,000

frequent spontaneous bleeding occurs with what platelet count

<10,000

describe acute immune idiopathic thrombocytopenic purpura (ITP)

childhood disease withhh acute onset 2 weeks post virus autoantibodies (IgG) against platelet Ags (GpIIb-IIIa or GpIb)

describe chronic immune (refractory) idiopathic thrombocytopenic purpura (ITP) of adults >6 months

autoantibodies (IgG) against platelet Ags (GpIIb-IIIa or GpIb)

what is associated with Shiga-toxin producing E. coli

Hemolytic Uremic Syndrome

what strain of E. coli is associated with HUS

O157:H7

HELLP Syndrome

hemolysis, elevated liver enzymes, low platelet (in pregnant women with HTN)

majority of people with vWF disease have type __ and it's MILD

Christmas Disease

Hemophilia B (Factor IX deficiency)

Warfarin (Coumadin) creates ____ deficiency

vitamin K dependent factor deficiency

condition initiated by release of tissue factor into circulation--causes all clotting steps to occur simultaneously everywhere

DIC

what is seen in DIC? PT: PTT: decreased: release of products from fibrinolysis:

prolonged prolonged factors V and VIII d-dimer and fibrin split products

microthrombi from DIC in adrenal cortex causes

Waterhouse-Friderichsen syndrome

microthrombi in pituitary causes what

Sheehan postpartum necrosis

how to you differntiate between DIC and TTP

DIC has prolonged PT and PTT

what color tube do you use for electrolytes, proteins, lipids, and drugs

red

what color tube do you use for CBC, sed rate

purple

what color tube do you use for PT and PTT, coag studies

blue

what color tube do you use for blood cultures

yellow

primary amyloidosis: associated diseases: precursor protein:

monoclonal plasma cell proliferations Ig light chains--chiefly gamma

secondary amyloidosis: associated diseases: precursor protein:

chronic inflammatory conditions SAA

hemodialysis-associated amyloidosis: associated diseases: precursor protein:

chronic renal failure beta2-microglobulin

systemic senile amyloidosis: associated diseases: precursor protein:

----- Transthyretin

senile cerebral amyloidosis: associated diseases: precursor protein:

Alzheimers APP

medullary carcinoma of thyroid amyloidosis: associated diseases: precursor protein:

---- Calcitonin

islets of langerhans amyloidosis: associated diseases: precursor protein:

T2DM Islet amyloid peptide

anti-DNA topoisomerase I

Systemic Sclerosis

Anti-Scl-70

Systemic Sclerosis

Anti-Centromere

CREST syndrome (limited scleroderma)

Anti-Jo-1

Autoimmune Myositis

Anti-Ro, Anti-La

Sjogren syndrome

anti-histone

drug induced LE

anti-smith, anti-dsDNA, anti-Ro, anti-La

SLE