Path I Midterm Flashcards
Pathology
the study of nature and cause of disease which includes changes to structure and function
pathophysiology
study of abnormal functioning of diseased organs
etiology
cause
every disease has an etiology but, most times, is unknown
idiopathic
etiology unknown
ankylosing spondylitis
ossification of the all the ligaments of the spine
DISH
AKA Forestier’s disease
diffuse idiopathic skeletal hyperostosis
results in ossification of the anterior longitudinal ligament
Congenital etiology
genetic information is intact, but other factors interfere with normal embryonic development
Acquired etiology
everything that is not genetic or congenital
examples include emphysema, herpes
Genetic etiology
damaged or altered genetic material is responsible for some structural or functional defect
symptom
subjective feeling
like pain, dizziness, tingling
sign
objective finding
ie blood pressure, temperature
syndrome
characteristic combination of signs and symptoms associated with a particular disease
raynaud’s syndrome
vasoconstriction of peripheral arteries of the fingers, thus no blood flow to fingers
no blood flow into the fingers, followed by no blood flow out of the fingers
fingers are white, then blue, then red
Sjogren’s syndrome
autoimmune damage to exocrine glands which results in dryness of mucous membranes which thus weakens the body’s first line of defense
usually a manifestation of rheumatoid arthritis or SLE
acute disease
short duration, quick onset, severe symptoms
chronic disease
lasts more than 6 weeks
has a more subtle onset
pathogenesis
mechanism of development of a particular disease
local disease
confined to one region of the body
ie stomach cancer
local diseases can become systemic
focal damage
damage is limited to distinct sites within a diseased organ
diffuse damage
damage distributed uniformly within the organ
systemic disease
considered systemic if it involves other organs and systems
diagnosis
identification of a patient’s specific disease
prognosis
theory of the outcome of the disease
deficiency
lack of substance necessary to the cell
primary nutrient deficiency
lack of specific components in the food
pellagra
lack of vitamin B3
casel’s necklace rash
scurvy
lack of vitamin c
beri beri
lack of thiamin (B1)
secondary nutrient deficiency
necessary nutrient is present in the diet but cannot be absorbed
pernicious anemia
lack of RBC’s in the blood from an inability to absorb vitamin B12 due to a lack of secretion of intrinsic factor by the stomach
intoxication
poisoning, toxins, or the presence of a substance that interferes with cell function
exogenous toxins
enter the body from outside
can come from infection, chemicals, or an overdose of medication/vitamins
endogenous toxins
created within the body
genetic endogenous toxins
can occur via accumulation of a normal metabolite or the activation of an alternative pathway
alkaptonuria
homogentisic acid is an intermediate of phenylalanine metabolism that builds up in the cartilage
causes onchrosis of the vertebral column
characterized by calcification of the IVD’s
blue ears is another symptom
onchrosis
deposition of homogentisic acid in the IVD’s
phenylketonuria
activation of an alternate pathway in phenylalanine metabolism
the enzyme that converts phenylalanine to tyrosine is nonfunctional leading to a build up of phenylpyruvic acid in the blood
gout
accumulation of metabolic byproducts
uric acid is a byproduct of purine metabilism, hyperuricemia leads to gout
uric acid salts are deposited in the joint capsules as the kidney cannot adequately remove the uric acid from the blood
Cell trauma
loss of structural integrity can come from : direct contact hypo/hyperthermia mechanical pressure (tumor/high intensity sound) microorganisms (malaria)
hyrdopic change
aka hydropic degeneration
reversible change
cell injury causes a functional inability to produce enough ATP
this causes cell swelling as sodium cannot be actively pumped out
steatosis
fatty changes
accumulation of triglycerides in parenchymal cells, pushing cell contents to the periphery and causing lysis in some cases
alcoholism= fatty liver, can also happen in the kidneys, skeletal muscle, and heart
residual bodies
fragments of bacteria or cellular organelles found in an injured cell as a result of failure to digest old organelles or bacterial resistance to some lysosomal enzyme
more residual bodies=more cellular disfunction
lipofuscin granules
aka lipochrome
complexes of protein and lipid that are derived from free-radical peroxidation of polyunsaturated lipids of subcellular membranes
these complexes are undigestible and are called brown atrophy, a wear and tear (aging) pigment
hemosiderosis
associated with deposition of hemosiderin in many organis and tissues in the cases of systemic overload of iron
the pigment of these tissues can be changed, however the function of these tissues is not affected
hemochromatosis
can be genetic or congenital
7-8 times the normal amount of iron in the blood leading to damage of the liver and pancreas and can also interfere with DNA (cause neoplasm)
can lead to hemolytic anemia
Wilson’s Disease
genetic, mostly seen in males
accumulation of copper ions
copper goes to the liver and is bound to alpha 2 globulin to form ceruloplasmin and would normally be excreted in the bile, but doesn’t like the liver in this case
D penicillamine is used to chelate the copper ions
kayser-fleischer rings
copper deposition in the limbus of the cornea
hyalinization
accumulation of hyaline (a glass like protein)
considered an irreversible change by our lecturer, but officially classified as reversible
reabsorption droplets
intracellular hyaline in the proximal tubules
causes proteinuria
dutcher bodies
intranuclear hyaline inclusions
russell bodies
intracytoplasmic inclusions of immunoglobulins when a patient has lymphoplasmacytic lymphoma aka waldenstron macroglobulinemia
blood becomes hyperviscous
Mallory bodies
aka mallory alcoholic hyaline
intracytoplasmic hyaline inclusions within the hepatocytes of alcoholics
hyaline arteriosclerosis
hyalinization in arterioles caused by long term hypertension or diabetes mellitus
makes the arterioles brittle/ may obstruct the lumen and could lead to intracerebral hemorrhagic stroke or ischemic stroke
nephrosclerosis
hardening of the kidney as a result of hyaline deposition with chronic hypertension or diabetes mellitus
huntington’s disease
genetic etiology
loss of striatal nuclei which control motion
presents around 30-35 years of age
chorea
rapid, jerky, involuntary movements of the face and extremities
Down’s Synrome
aka trisomy 21
third copy of chromosome 21
chromosomal abnormality resultsing in mental handicap and a characteristic physical appearance
teratogen
an agent that causes a physical abnormality in a developing embryo or fetus
Fetal Alcohol Syndrome
birth defects resulting from high alcohol consumption by the mother during pregnancy
highest teratogenic effect in the first three days, then the first trimester of pregnancy
thalidomide
sleeping medicine prescribed to pregnant women to prevent morning sickness
babies were born with deformed extremities
ionizing radiation
could result in the production of free radicals that can destroy cell membranes
Waldenström Macroglobulinemia
aka hyperviscosity syndrome or pymphoplamocytic lymphoma
a type of lymphoma due to a monoclonal tumor (cancer of B lymphocytes resulting in overproduction of IgM)
russel bodies and dutcher bodies are commonly seen with this type of cancer
intercellular deposition
between or among cells
dangerous, can obstruct the lumen of small vessels
ischemia/ infarction leads to tissue necrosis
increased brittleness of vessels can lead to intracerebral hemorrhagic stroke
amyloid
the generic term for a variety of proteinaceious materials that are abnormally deposited in tissue interstitium in a spectrum of clinical disorders
amyloidosis
causes death within a year or two
caused by different cells of the body and effects different organs
primary is idiopathic
secondary is the result of another disorder like autoimmune disease (effects liver, brain, kidney, and heart muscle most often)
alternative metabolism
use of normal route is impossible due to damage, so the cell uses another pathway
ie using an alternate energy pathway in the absence of oxygen
hypertrophy
call/organ enlargement in response to increased demands
ie the heart- increased resistance due to hypertension
atrophy
shrinkage due to decreased demands
poliomyelitis
contagious (viral)
irreversible, lose anterior horns of spinal cord
muscles atrophy without neuronal stimulation
Hashimoto’s thyroiditis
#1 cause of hypothyroidism in USA autoimmune, idiopathic antibodies attack TSH receptors on the thyroid causing a slow loss of thyroid function, atrophy and loss of the gland
Graves Disease
autoimmune, idiopathic
occurs 50% more often in females
Antibodies bind to TSH receptors and mimic TSH stimulating excess thyroid hormone production
gland hypertrophies due to increased demand
characterized by toxic goiter and sometimes exopthalmus
blebs
out pouching of the cell membrane
1-2 blebs is reversible, but too many becomes an irreversible change
Myelin figures
disruption of the cell membrane
a couple is reversible, but too many will overwhelm the cell
karyolysis
dissolution of the nucleus
irreversible
pyknosis
condensation of the nucleus
irreversible
karyorrhexis
fragmentation of the nucleus
necrosis
death of cells or tissues through injury or disease, especially in localized areas of the body
coagulative necrosis
characterized by denaturation of cytoplasmic proteins, breakdown of cell organelles, and cell swelling
implies preservation of the basic outline of the cells for at least a couple days which allows the body to attempt to heal
fibrosis replaces dead tissue
Necrosis resulting from myocardial infarction
ischemia results in coagulative necrosis and the heart undergoes fibrosis to heal the dead tissue
White infarct
occurs in tissue with a single blood supply
ie the heart
red infarct
occurs in tissue with two or more vessels supplying it
ie lungs or liver
liquefactive necrosis
complete digestion of dead cells resulting in the transformation of the tissue into a liquid viscous mass
ie stroke
caseous necrosis
“cheese like”
on a microscopic scale: amorphous granular debris seemingly composed of fragmented coagulated cells, enclosed within a distinctive inflammatory border known as a granulomatous reaction
What can cause caseous necrosis?
tuberculosis in the lungs- forms cavities, physical disruption of the tissue and vessels
leprosy- chronic bacterial infection causing nerve damage, contagious
gummatous necrosis
caused by tertiary syphilis or general paresis
occurs in the CNS
Syphilis
aka lues
goes through three stages, can be congenital or an STD
tertiary syphilis- neurosyphilis causes gummatous necrosis in the brain and posterior column of the posterior horn of the spinal cord
General paresis
aka general paresis of the insane
occurs in the grey matter of the brain leading to dementia
Zenkers necrosis
severe waxy or glassy necrosis of the skeletal muscles in acute infectious diseases like typhoid or cholera
Fat necrosis
aka steatonecrosis
necrosis of the adipose tissue, characterized by formation of calcium soaps when fat is hydrolyzed into glycerol and fatty acids
pancreatonecrosis
fatal
example of steatonecrosis
gall stones obstruct the bile duct after it merges with the pancreatic duct
pancreatic and bile juices stay in the pancreas and lead to necrosis
Fibrinoid necrosis
occurs in the walls of blood vessels when endothelial or smooth muscle cells are injured or dying
common in immunopathologies
aschoff’s nodes
seen with rheumatic myocarditis from rheumatic fever
nodes seen in intermuscular connective tissue, surrounding inflammatory cells
Gangrenous necrosis
aka gangrene
serious, potentially life threatening condition that arises when a considerable mass of body tissue dies
dry gangrene
a condition when coagulation is sustained
can be caused by ischemia, atherosclerosis and diabetes mellitus
systemic sclerosis
aka scleroderma
vasospasm and obliteration of small blood vessels leads to dry gangrene (ischemia)
diabetic microangiopathy
complication of diabetes
seen in the extremities, kidneys, and eyes
cause of dry gangrene
Buerger’s disease
aka thromboangitis obliterans
seen in smokers
results in development of antibodies that attack endothelial cells
cause of dry gangrene
Wet gangrene
occurs if the enzymes of invading phagocytic cells break down the necrotic debris and produce some liquefaction
often occurs with blockage of venous flow and in the presence of certain bacteria (clostridium perfringes, bacillus fusiformis)
polyarteritis modosa
systemic vascularitis of the fingers
naked bones
gas gangrene
bacterial infection produces gas within the tissues
seen with anaerobic streptococci and clostridium perfringes
strangulation (hernia) of the stomach or intestines can cause this
apoptosis
pathway of cell death that is induced by a tightly regulated intracellular program in which cells destined to die activate enzymes to degrade their own nuclear DNA, nucleus, and cytoplasmic proteins
normal conditions of apoptosis
programmed cell death during embryogenesis
menstruation
cell death induced by cytotoxic t cells
pathological conditions of apoptosis
cell injury in viral diseases
pathologic atrophy in parenchymal organs after duct obstruction
anthracosis
deposition and accumulation of carbon in the tissues
this term is used to describe a condition, and is not a condition in and of itself
coal worker pneumoconiosis
lung disease
lung tissues are modified due to reaction of inhalation of particles, leading to connective tissue deposition
dystrophic calcification
deposition of calcium salts into necrotic or atrophic tissues
gohns focus
aka primary TB complex
activation of T helper cells leads to a granulomatous reaction
when the body kills the bacteria, it also kills the tissue which then becomes occupied by calcium salts
metastatic calcification
deposition of calcium into tissues that are not necrotic or atrophic
Causes of Metastatic calcification
increased PTH secretion destruction of bone excess vitamin D sarcoidosis renal failure in secondary hyperparathyroidism
Ischemia
lack of blood supply to tissue or organ
brain, lung, kidney, splee, heart muscles, are most vulnerable
liver is not vulnerable
labile tissue
tissue with a high rate of mitosis or cell turnover
ionizing radiation
labile tissue is most vulnerable
permanent tissue like bone is not vulnerable
viral infection
intracellular parasites
usually have a site of preference so tissue vulnerability varies by virus
Cardinal signs of inflammation
rubor- redness calor-heat dolor-pain tumor- swelling functio laesa- loss of function
two components of inflammation
vascular- hyperemia (increased blood flow) and increased permeability in the blood vessels
cellular- blood cells move to the site of inflammation
exudate
inflammatory fluid at the site of inflammation
protein rich, bloodcells and microorganisms may be present, provides a space for healing the damaged tissue
transudate
not a protein rich fluid
hyperemia
vasoconstriction followed immediately by vasodilation
passive enlargement of capillaries to 20-30% larger than normal
increased blood hydrostatic pressure
stasis
slowing of blood flow so that its movement in capillaries and venules stops
increased permeability of vessels
constriction of endothelial cells increases the size of the capillary pores
albumin moves into tissue, bringing fluid with it
Normal blood protein values
albumin 55%
globulins 40-45%
Fibrinogen 5%
Benefits of inflammation
swelling leads to pain which makes the person stop moving the injured body part
dissolution of toxins
exudate brings antibodies
phagocytic cells ingest pathogens
serous inflammation
large amount of watery exudate
response to mild injury, only fluid escapes to the interstitial fluid
ie runny nose with common cold or blister
fibrinous inflammation
fibrinogen in the exudate starts to form fibrin strands
can be dangerous
ie rheumatic pericarditis- can hear friction rubs in the pericardial sac
suppurative inflammation
characterized by the presence of pus
contains enzymes and cells
pus can be a source of infection and transmit disease to other parts of the body
abcess
type of suppurative inflammation
localized accumulation of pus that develops at a focus when an agent of injury can’t be quickly neutralized
cellulitis
suppurative inflammation
diffuse, widespread suppurative inflammation
empyema
a type of suppurative inflammation that occurs in two cavities: the subarachnoid space and pleura
hemorrhagic inflammation
accumulation of RBC’s at the site of inflammation
RBC’s do not participate in the inflammatory response
Leukocyte emigration
active
an outpouring of a large amount of WBC’s from the blood
only occurs in postcapillary venules
WBC’s attach to lumen receptors and move to gap in the endothelial cells and enter the interstitial space
axial blood flow
normal blood flow
cells move down the center of the lumen in a column with the largest cells in the center
margination
when WBC’s are positioned at the periphery of the column as a result of the redistribution that occurs when RBC’s move to the center of the column
pavementing
leukocyte adherence to the endothelial cell surfaces
diapedesis
a passive process where RBC’s move outside the vessel with or without inflammation
Polymorphonuclear cells
all are granulocytes
neutrophils, eosinophils, basophils
neutrophils
normally 55-60% in circulation
first to arrive at site of inflammation
3-4 lobes in nucleus
life span is 8 hours to 3 days
eosinophils
red granules
2 lobes in the nucleus
normally 2-4% in circulation
basophils
normally 0.5-1% in circulation
blue granules
2 lobes in the nucleus
mononuclear cells
all are agranulocytes
lymphocytes and monocytes
lymphocytes
typically 20-25% in circulation
monocytes
typically 4-8% in circulation
largest cells in the blood
second to arrive at the site of inflammation
lifespan is for years
monocyte life cycle
monocytes –> macrophages - APC’s (antigen presenting cells)
stages of phagocytosis
recognition and attachment- occurs through chemotaxis
engulfing- use of pseudopods and formation of vesicles
ingestion- killing and degradation/fragmentation
exocytosis
oxygen independent phagocytosis
uses enzymes to digest proteins (lysosomes)
defensin
defensin
antibody like substance in neutrophils
oxygen-dependent phagocytosis
uses anions to produce free radicals, found in the granules of phagocytic cells
superoxide, hypochlorite, and hydrogen peroxide are used
chronic granulomatous disease
rare genetic defect in phagocytes
phagocytic cells are not able to produce free radicals
children die young from chronic infection
Chediak-higashi syndrome
genetic disease
impairment of phagocytic cell motility
WBC’s cannot degranulate (release contents of granules)
Initiators to the Inflammatory response
direct stimulus to mast cells microbial products exposure of basement membrane of connective tissue components complement activation deposition of antibody/antigen complexes disruption of vascular integrity substances released from injured cells
Functions of Histamine
vasodilation
increased vessel permeability
bronchospasm
increased mucous production
Where is histamine released from?
Primarily released near the site of inflammation
released from granules in response to physical injury or type I hypersensitivity
from basophils and platelets in circulation
from mast cells (basophils fixed in tissues)
Major reservoirs of histamine in the body
basophils, past cells, and platelets
Serotonin
aka the hormone of pleasure
produced by platelets
similar function to histamine
Substance P
neuropeptide produced by nervous fibers in the CNS and PNS
produced by lungg and GI nervous tissues
Functions of substance P
promote production o pain
regulate blood pressure
increase blood vessel permeability
Nitric oxide
aka endothelial-derived releasing hormone
mediator of the sympathetic nervous system
Where is nitric oxide produced
endothelial cells of blood vessels, macrophages, and brain neurons
functions of nitric oxide
vasodilator
prevents neutrophil recruitment to site of inflammation
inhibit WBC pavementing
inhibitor to the cellular component of inflammation
Eicosanoids
arachadonic acid metabolites
from phospholipids in cell membranes
includes prostaglandins, leukotrienes, and lipoxins
What are the major producers of eicosanoids?
neutrophils and macrophages
Prostacyclin
PGI2
produced by endothelial cells
inhibits platelet aggregation and causes platelet aggregation
Thromboxane A2
TXA2
produced by platelets
functions opposite to PGI2
causes vasoconstriction and promotes platelet aggregation
What are the functions of PGD2, PGE2, and PGF2
vasodilation
potentiate edema
allows for pain perception and fever
produced by macrophages and less by neutrophils
Normal physiological function of COX-1
Regulate the amount of fluid and salt in the kidneys
protect the GI tract from ulceration and inflammation
What two enzymes produce all prostaglandins?
cyclooxygenase 1 and 2
What inhibits COX-1
NSAIDS
consequences of inhibiting COX-1
can lead to kidney problems and stomach irritation/ulceration
HCl levels rise in its absence
Function of COX-2
produces extra prostaglandins when needed
COX-2 inhibitors
Vioxx, celebrex, meloxicam
used to prevent the side effects of NSAIDS
vioxx could result in thrombosis, throboaneurysm, MI (no longer used)
Enzyme that produces leukotrienes
5-lipoxygenase
Function of leukotrienes
vasoconstriction (balance out vasodilation)
bronchospasm
increased permeability
Enzyme that produces lipoxins
12-lipoxygenase
Function of lipoxins
vasodilation
inhibit neutrophil chemotaxis
stimulate monocyte adhesion
What inhibits Eicosanoids?
corticosteroids
Tumor necrosis factor
produced predominantly by activated macrophages
induces acute inflammatory response
What inhibits tumor necrosis factor
medication for RA, ankylosing spondylitis
may lead to lymphomas
what produces IL-3 and IL-6
predominantly by helper T cells
Function of IL-3 and IL-6
Induces acute inflammatory response
Acute phase of inflammation response
fever, anorexia, increased sleep increased c-rp increased ESR (erythrocyte sedimentation rate) vasodilation neutrophilia
what protein is increased during the acute phase of inflammation
C-RP c-reactive protein
Lymphangitis
appears as a red line on the skin
inflammation of the lymphatic vessels
injury with infection
will go to the nearest lymph node
Lymphadenitis
enlarged and painful lymph node due to accumulation of a pathogen
nonpainful lymph nodes- cancer
bacteremia
infection/bacteria in the blood
very dangerous
septicemia
accumulation of toxic products of bacterial metabolism in the blood
leukocytosis
increased leukocytes in the blood due to infection
>9,000 leukocytes per cubic millimeter
neutrophilia
greater than 60%
lymphocytosis
indicates a possible viral infection
above 30% blood content
Eosinophils
normally 2-4%
indicates a type I hypersensitivity reaction or parasitic infection
Complement
C3a, C4a, and C5a
promotes secretion of histamine from the granules of mast cells
participate in inflammation to a certain degree
Hageman factor
aka clotting factor XII Hageman factor (clotting factor XII)
Functions of prekellikrein
vasodilation, promotes the vascular component of inflammation
short-lived (5-10 minutes)
monocytosis
indicative of a chronic bacterial infection
can increase up to 50% of circulating WBC’s (normally 4-8%)
infectious mononucleosis –> lymphadenopathy of the neck and upper thoracic lymph nodes
Juveline RA
hands and joints swollen
inflammation can destroy tissue and bone
Chronic Inflammation
> 6 weeks in duration
usually does not have exudate
Cell content of exudate in chronic inflammation
When present:
there will be only macrophages, no neutrophils, as they have a shorter lifespan
aseptic osteonecrosis
compressed blood vessels lead to infarction
dissolution of bone without infection
effects of chronic kidney inflammation
healthy tissue begins to be replaced by connective tissue
the connective tissue shrinks giving the kidney a granular appearance
Agents typically involved with chronic inflammation
organic: microorganisms- mycobacterium tuberculosis, m. leprae, listeria, treponema pallidum, brucells
inorganic: asbestos, silica, beryllium, dusts
Nonspecific chronic inflammation
a diffuse accumulation of macrophages and lymphocytes develops at the site of injury
granulomatous inflammation
formation of a granuloma
develops in TB
Layers of a granuloma from deep to superficial
pathogen epitheliod cells (derived from macrophages) lymphocytes fibroblast connective tissue
Four major components of healing
regeneration
repair
revascularization
surface restoration
Regeneration
tissue is replaced from parenchyma by cell division
new tissue assumes normal function
ideal response to tissue loss
Three types of tissue
each has different patterns of regeneration
labile, stable, and permanent
Labile tissue
divides continually to replace cells that are constantly being depleted by normal processes
ie mucous membranes, red bone marrow
Stable tissue
cells divide, but slowly beyond adolescence when normal development is complete
mitosis rate increases when damaged tissue must be replaced
ie glands, osteoblasts, smooth muscle fibers, and vascular andothelium
Permanent tissue
loses all mitotic ability after birth
loss of which results in functional loss
cells lost are replaced by scar tissue
ie heart muscle, nervous tissue
Repair
fibrous scar tissue fills the gaps left by the loss of damaged tissue
restores strength and structural integrity of damaged tissue that cannot regenerate
Fibrosis
formation of collagen fibers
fibroblasts in stroma secrete procollagen that eventually is activated into collagen
collagen filaments are then bundled together to form fibers
revascularization
aniogenesis occurs in the loosely gelled, protein-rich exudates that form at the site of damage
andiogenesis
production of new blood vessels
surface restoration
restoration of the protective epithelium that covers body and organ surfaces
Primary healing
healing of an incision or severing wound of the skin
secondary healing
wound edges are not closely apposed
contracture
complication of healing
newly formed collagen demonstrates an exaggerated wound contraction response as it matures
adhesions
complication of healing
joining of serous membranes leads to restriction of movement in structures
dehiscence
complication of healing
breaking open of a healing wound, possibly due to pressure on the wound
keloids
complication of healing
irregular masses of scar tissue that protrude from the surface of skin, which results
from the over production of dermal collagen during healing.
proud flesh
complication of healing
overproduction of granulation tissue
suture complications
complication of healing
interruption of epithelium
