MT1 GOOD Flashcards
In ischemia leading to cell injury, decreased O2 impairs _____ in ____. This effects the plasma membrane because it decreases ___ which decreases ability of membrane to maintain homeostasis. Can also cause detachment of _____ from ____
- oxydative phosphorylation in mitochrondria
- Decreases ATP.
- Detachment of ribosomes from RER
When ROS leads to cell injury, these occur…
lipid _____, protein (membrane) _____, reacts with ____ and ____ to induce ______
-lipid perOXYdation
-protein cross-linking
-thymidine and guanine
=induces single strand DNA breaks
What is the “final” common pathway in cell injury?
What does it activate?
- Increased cytoplasmic Ca2+
- Activates degradative enzymes (phospholipases, proteases, ATPase)
What does a cell that has reversible cell injury look like? Why?
- Pale and swollen
- Plasma membrane injury leads to increased intracellular Na+ that leads to gain in water
A cell doesn’t show a nucleus, but retained an eosinophilic outline of cell, which kind of necrosis is this?
Coagulative necrosis
A cell looks like a amorphous pink granular material within a ring of granulomatous inflammation, which kind of necrosis is this?
What does the tissue look like (gross)?
Which disease is this associated with?
Caseous necrosis
- White and cheesy
- TB
Which kind of necrosis causes tissue to look totally digested by lysosomal enzymes during acute inflammatory response?
What is this often associated with?
Liquefactive necrosis
-bacterial/fungal infections (abscesses and gangrene)
You look in microscope and see “soap bubbles”, what kind of necrosis?
fat necrosis
Necrosis vs. Apoptosis.. Which is multiple cells: Which causes cell swelling: Which is ATP dependent: Which causes inflammation:
multiple cells: necrosis
swelling: necrosis
ATP dependent: apoptosis
Inflammation: necrosis
What does the Bcl-2 gene family regulate?
What do BCL-2 and BCL-x genes do?
Bax and Bak?
- Membrane permeability of mitochondria
- INHIBIT apoptosis
- STIMULATE apoptosis
Cytochrome-c is released from _____.
Serves to:
In the end, what effect does it have on apoptosis?
- outer mitochondrial membrane
- disrupts Bcl-2
- FAVORS apoptosis
What are capsases?
the executioner of apoptosis
Patient has iron deficiency, what type of cellular “growth” will he have in his thyroid?
hypertrophy
Hyperplasia can be secondary to:
estrogen treatment for prostate cancer
Erythrocyte ______ can follow ectopic production of erythropoietin renal cell carcinoma
hyperplasia
Vitamin A deficiency can cause (hypertrophy/hyperplasia/metaplasia)
metaplasia
What is steatosis?
Fat accumulation (Fatty liver)
Where does cholesterol accumulate and what can it cause?
In macrophages
-Xanthoma in skin
Alzheimer’s disease is an accumulation of ____
protein
Glucose/glycogen accumulation is abnormal glycogen metabolism due to ______
enzyme deficiency
Pigment accumulations..
Lipofuscin is due to:
Hemosiderin:
Bilirubin:
Lipofuscin: ROS peroxidation
Hemosiderin: excess iron locally due to hemorrhage
Bilirubin: end product of heme metabolism. Obstructed bile flow
Vascular changes of inflammation:
Chemical
What is fever mediated by?
Vascular: heat, redness, swelling
Chemical: pain, loss of function
-IL-1, TNF, PGE2
During inflammation what causes vasodilation? what maintains it?
NO
prostaglandins (PG_)
Transudate:
Exudate:
Trans: low protein. Fluid accumulates due to change in pressure
Ex: HIGH protein. Indicative of tissue and endothelial cell damage
Cellular changes during inflammation…
Endothelial cells are activated by:
Leukocyte extravasion is mediated by:
Leukocytes are activated by:
- histamine, thrombin
- Integrins (ICAM, VCAM)
- Arachidonic acid
Phagocytosis attachment is mediated by _____ on targets and specific ____ receptors.
What happens to lysosome when it fuses with phagosome?
Opsonins
Leukocyte
-degranulation
What are the first cells of inflammation?
After phagocytosis and digestion, they undergo ____.
They release ____ and ____
Neutrophils (PMNs)
- Apoptosis
- ROS and Lysozyme
Which cells of inflammation present antigen to T cell
Monocytes (macrophages/histocytes)
Granulomous inflammation (chronic inflammation) is linked to ______ hypersensitivity immune reaction.
What kind of cells will it form?
How is it healed?
What can cause it?
delayed-type IV
- multinucleated giant cells (Langhans)
- fibrosis
- TB, cat scratch fever
What is the source of histamine?
Causes vaso___ and ____ vascular permeability
Mast cells
- vasodilation
- INCREASES vascular permeability
First vs second intention wound healing.
In second intention, wound contraction is due to:
First intention is blood clot–> neutrophils..etc.
Second has more inflammation and more granulation tissue
-myofibroblasts
What is thrombosis?
Arterial thrombi are which color?
Where do the tend to occur?
Venous thrombi are which color?
Where do they tend to occur?
BLOOD CLOT
Arterial= pale white
Occur at sites of turbulence and lodge in smaller arteries causing infarction
Venous= red
Occur in deep veins in legs
Fate of thrombi... Propagation: Embolization: Dissolution: Organization:
- Propagation: enlarged by additional fibrin/platelet deposition
- embolization: thrombus breaks loose
- dissolution: lysis by fibrinolytic activity
- organization: ingrowth of fibroblasts and smooth muscle cells, leads to deposition of collagen (replacing the fibrin) and recanalization, which may reestablish flow through thrombus
DIC ends up accumulating:
fibrin split products
Thromboemboli that lodge in _____ arteries usually arise from _____
pulmonary
deep veins in the legs
What predisposes fat emboli?
Air emboli:
Amniotic fluid:
Atherosclerotic (hardening of arteries):
fat: fracture of large long bone
Air: chest wall injury, decompression sickness (bends)
Amniotic: associated with DIC
Atherosclerotic: debris from central core of atherosclerotic plaque
What color infarcts occur in solid organs (where tissue density limits blood seepage from adjacent vascularization)
What color infarcts are caused by venous occlusion
White infarcts
red infarcts
What kind of necrosis results from infarcts in the brain?
liquefactive (NOT coagulative)
Anaphylactic shock is mediated by:
What kind of shock is caused by anesthesia?
IgE
neurogenic shock
Nonprogressive stage of shock:
Progressive stage:
Nonprogressive: compensatory
Progressive: inadequate perfusion w/ metabolic imbalances such as acidosis (increased lactic acid)
What are the two most common areas of ischemic necrosis in the brain?
Hippocampus and cerebellum
Clinical manifestations of shock:
tachycardia, HYPOtension, cool clammy skin, decreased urinary output, confusion , acidosis (increased lactic acid)
Nephrotic syndrome is an example of which edema?
Decrease in plasma osmotic pressure
What is congestion and what is it often accompanied by?
Examples of congestion?
Congestion: increased RBCs (impaired venous return)
-Accompanied by edema
-CHF, tourniquet
Types of hemorrhages..
Petechia, purpura, ecchymoses
Petechia: 1-2mm
Purpura: 3-9mm
Ecchymoses: >1cm
What is the cofactor for binding platelets to collagen (platelet adhesion).
Platelet secretion is mediated by
von Willebrand factor
-ADP + thromboxane A2
Thrombomodulin binds to ____ and this complex activates _____
thrombin
protein C
FibrinoLYSIS occurs by the activation of _____.
What does plasmin do?
Plasmin
Breaks down fibrin (hence the lysis…)
How does lead-induced anemia work?
What kind of anemia do they develop?
What does lead compete with?
lead has high affinity for enzymes involved in the synthesis of hemoglobin, which blocks or hinders the incorporation of iron into the molecule.
- Microcytic hypochromic anemia
- Competes with Ca2+
Radiation injury…
TARGET effect:
Indirect effect:
Target: direct hit on DNA, causing mutations
Indirect: production of free radicals
Marasmus is deficiency of ____. ____compartment is depleted. Can cause ____ and ___deficiency (especially T cell). What is a common finding?
Marasmus: deficiency of Caloric intake (starvation).
- Somatic protein compartment (skeletal m.)
- Can cause anemia and immune deficiency.
- Common finding=thrush
Kwashiorkor is:
This is the most common form of ___ in Africa. Is this more or less severe than marasmus?
What organ does this mess with?
greater deficiency of protein than total calories.
- most common form of Protein-Energy Malnutrition
- MORE severe
- Liver
What is Protein-Energy Malnutrition in cancer patients called?
Cachexia
If you have dry eye, and can also affect respiratory/urinary tracts, and immune system (can cause measles, pneumonia, etc.), what is wrong with you?
Vitamin A DEFICIENCY
If you have blurred vision and fissured lips, what’s wrong?
Vitamin A TOXICITY
If you have impaired collagen synthesis –> impaired capillaries + venules (hemorrhage in gingiva…wound healing is impaired), what’s wrong with you?
Vitamin C DEFICIENCY
What causes scurvy?
Vitamin C DEFICIENCY
What can give some protection from gastric and esophageal cancers (and enhance iron absorption)?
Vitamin C
What is special about pulmonary (lung) blood supply?
Dual blood supply (pulmonary and bronchial)
Vocal cords are lined with:
Large airways lined with:
- Vocal cords: stratified squamous epi (SSE)
- Large airways: psuedostratified ciliated columnar epi (PCCE)
Where is the mucociliary apparatus?
Where are the alveolar macrophages?
lower airway
lymphoid tissues
Clinical manifestations of pulmonary disease.. Hemoptysis: Dyspnea: Atelectasis: Pneumothorax: Pleural effusion:
Hemoptysis: coughing up blood
Dyspnea: shortness of breath
Atelectasis: loss of lung volume (inadequate expansion of airspaces)
Causes of pulmonary edema:
Increased vascular pressure
Hypoproteinemia (low protein)
Vascular damage
Px is having trouble exhaling, what’s the mechanism?
(emphysema) imbalance between protease and anti-protease enzymes
What is the disease when you have increased mucus glands, chronic inflammation, fibrosis, narrowing of airways
Chronic bronchitis
What is a chronic infection w/ permanent (large) airway dilation
bronchiectasis
Asthma is increased irritability of ___ in bronchi. Inflammation caused by ______. Antigen binds to surface ____
S.m.
Eosinophils
IgE
What pulmonary infection affects full lobe of lung
bacterial pneumonia (streptococcus pneumoniae). This affects HEALTHY adults
What pulmonary infection causes interstitial inflammation, mononuclear cells, congestion and hyaline membranes (diffuse alveolar damage)
viral (walking) pneumonia
What pulmonary infection develops rapidly and causes injury to endothelium and alveolar epi
ARDS (acute respiratory distress syndrome)
Which pulmonary infection can cause cough and fever. Caused by ASPIRATION
Pulmonary abscess
What is the most common infectious cause of death in the world?
TB
Which pulmonary infection causes a caseating granuloma and Ghon lesion
TB
Granulomatous inflammation is common in TB, but is associated w/ many fungal infections such as _______ and
histoplasmosis
sarcoidosis
Squamous cell carcinoma and small (oat) cell are common cancers of:
the lung
What is pneumoconioses?
Inhaled particles induce fibrosis (scarring). 1-5um is the worst.
What is the most prevalent form of occupational disease?
silicosis (silicon dust)
In cancer, which component determines the biological behavior of the neoplasm?
Parenchymal
For cancer, what is stroma
supporting tissue of tumor (supplied by host)
Benign tumors suffix:
Malignant mesenchymal suffix:
Malignancy of epithelial origin:
“oma”
“sarcoma”
“carcinoma”
Definitions…
Hamartoma:
Choristoma:
Teratoma:
- Hamartoma: proliferation of tissue normally found at that site
- Choristoma: collection of tissue not normally found at that site
- Teratoma: neoplasm derived from more than one germ layer
Are high grade/anaplastic malignancies poorly or highly differentiated
poorly
Well-differentiated (low-grade) malignancies resemble:
normal tissue
Difference of dysplasia and anaplasia in malignancies
dysplasia is disorderly, but non-neoplastic growth.
Anaplasia is most extreme distrubance in cell growth…poorly differentiated…faster growing
Which tumors have a fibrous capsule, benign or malignant
benign
What is the hallmark of malignancy
metastasis (secondary deposits of tumor at distant sites).
The larger and more anaplastic it is, the more likely to metastisis
What are the 3 methods of metastasis
- Seeding within body cavities (pluera)
- Lymphatic spread (carcinomas)
- Hematogenous spread (sarcomas…affects liver and lungs)
Inherited cancer syndromes are usually due to:
Autosomal ___
Some examples:
Defective DNA repair syndromes are autosomal ____
Example?
single gene mutation
autosomal DOMINANT
-retinoblastoma,
- recessive
- xeroderma pigmentosum
What are growth promoting cancer cells called.
Are they controlled?
protooncogenes
NO, they are UNcontrolled promoters of growth
What is the most common growth promoting signal-transducing protein in cancer?
What does it do?
RAS oncogene.
Normally inactive, but when mutated, stimulates constant cell proliferation
What growth promoting gene mutation causes Burkitts lymphoma (most common nuclear transcription factor).
What happens when it’s mutated?
MYC
Activates a kinase, therefore causing cells to divide rampantly
RAS and MYC are both growth____
promoting
Which cancer needs 2 “hits” and is a key player in regulation of the cell cycle
retinoblastoma
Most common target for genetic alteration in human tumors (found in every type of cancer):
Is that gene growth promoting or inhibiting
With loss/mutation of this drug, what happens to damaged DNA
TP53
Inhibiting (suppressor)
It goes unfixed
Overexpressed BCL-2 protein protects cells from apoptosis, which can result in
low-grade (well differentiated…slower growing) lymphoma
Are cancers usually one mutation or more
MORE, or everyone would have cancer!
~__% of newly diagnosed patients with solid tumors will present with metastasis
30%
Is carcinogenesis lethal/nonlethal genetic damage
NONlethal
Cancer cell proliferation….
What are CDKs important for?
important in determining whether a cell is going to enter the cell cycle.
Have atypical cells invaded into the host with carcinoma in-situ?
NO
Which cancers have lymphatic spread?
carcinomas
***End products of metabolic conversion in cancer are termed ____ carcinogens
ultimate
**What does prostacyclin do?
inhibit adhesion
Overall 5 year survival rate for all cancer types is
16%
Difference of a carcinogen (chemical) and promoter in cancer
carcinogen: initiator of mutation
promoter: drives replication
What is the latent time for radiation exposure to time of cancer
7-12 years
EBV (epstein-barr virus) is implicated in the pathogenesis of several malignancies including:
Burkitt’s lymphoma, B-cell lymphoma, Hodgkins lymphoma..
EBV=LYMPHOMA!!!!
Hep B virus is liked to development of:
hepatocellular carcinoma
What is an example of a paraneoplastic syndrome?
Non-bacterial thrombic endocarditis (NBDTE)
Cancer develops in immune competent patients by:
selective outgrowth of antigen-negative variants
Cancer Grading vs staging.
Which is more valuable in determining prognosis?
grading= aggressiveness (grade IV being least differentiated….worst)
Staging=extent/size/metastasis (IV is most disseminated..worst)
Staging is more important for prognosis
A mutation in the genes for adhesion molecules would NOT affect:
margination (slowing of blood)
What’s the problem with frozen section biopsy?
Prone to errors. Must do it right at time of surgery
What is a contusion
Bruise. Doesn’t break skin.
