Exam 4 General Info Flashcards
What is cell injury?
When the cells are stressed to the point that they are unable to adapt
What is apoptosis?
A programed cell death
What is necrosis?
A injury causing cell death that isn’t planned after the point of irreversibility
What is hypertrophy?
An increase in cell size
Where does hypertrophy occur?
It occurs in cells that are incapable of dividing (striated muscle cells in the skeletal muscles and the heart)
What commonly causes increased workload in hypertrophy?
Physiological stimuli or pathological conditions
Hypertrophy is characterized by what 2 protein synthesis?
Mechanical triggers such as stretching
Hormonal triggers such as adrenergic hormones (fight or flight)
What changes in the uterus during pregnancy?
The cells go through hypertrophy and become enlarged
What is hyperplasia?
An increase in the number of cells but not size
What are 3 physiological examples of hyperplasia?
Proliferation of the female mammary epithelium during puberty
Profiferation of connective tissue cells during wound healing
Regeneration of the liver (physiologic compensatory hyperplasia)
Physiological hyperplasia in female hormones?
Estrogen, progesterone, prolactin
Pathological hyperplasia in female hormones and male
Can cause cancer with hormone imbalances
What is atrophy?
Shrinkage of the cell size by the loss of cell substance
What are the 5 things cause atrophy?
Decreased workload
Loss of innervation
Reduced blood supply
Inadequate nutrition
Aging (senile atrophy)
Atrophy causes a decrease in cell size which is caused by?
Increased protein degradation
Or reduced protein degradation
What is metaplasia?
One cell type is replaced by another cell adult type
What 2 things usually causes metaplasia?
Chronic irritation
Inflammation
Examples of metaplasia?
Ciliated columnar epithelial cells of the trachea and bronchi help clear foreign matter and mucus
In smokers and vitamin A deficiency ciliated columnar cells are replaces by squamous epithelial cells which are more rugged and not ciliated
This leads to coughing and an increase in infections
Another example is Barretts esophagus
What does metaplasia usually lead to?
usually a precursor for cancer
can be reprogramming a stem cell and dosent replace (they keep dividing)
What is dysplasia?
Organization of cell is lost, they vary in size, number, shape and organization
What is dysplasia associated with?
Chronic irritation
Inflammation
Dysplasia is a precursor for what?
Cancer
- oxygen deprived (causes of cell injury)
Hypoxia - oxygen deficiency
Ischemia - loss of oxygenated blood supply to tissues
- cause of cell injury
Chemical agents - posions, air pollutants, CO, asbestos
- cause of cell injury
Infectious agents - viruses, bacteria, fungi, parasites
- cause of cell injury
immunological reactions - autoimmune diseases
- cause of cell injury
genetic defects - sickle cell anemia, familial hypercholesterolemia
- cause of cell injury
physical agents - trauma, heat, cold, electrical shock
- Nutritional imbalances (causes of cel injury)
nutritional deficiencies - calcium or vitamin
Excess nutrition
Diabetes - can be causes by obesity - excess blood sugar levels can damage cells
Atherosclerosis - can be caused by diet rich in fats - can result in blockage of arteries
- cause of cell injury
Aging - accumulation of damaging reactive oxygen species
What does ischemia mean?
Decreased oxygen to a tissue
What are the characteristics of reversable injury?
Cells start to swell and get larger
Fatty change - see lipid vacuoles starting to form
What are the characteristics of ireversible injury?
Mitochondria dysfunction - no ATP
Membrane dysfunction - around organelles and around the whole cell
Free radical formation leads to ?
Oxidation of cell structures and nuclear and mitochondrial DNA
Intraceullular Ca increase leads to ?
Enzyme, organelle, cytoskeleton depeltion / injury
ATP depletion leads to ?
Detachement of ribosomes from ER
Decreased protein synthesis
lipid deposition
Increase in anarobic metabolism
Glycogen storage and intracellular pH drops
decrease in sodium potassium pump
Increase of sodium and water in the cell
BAD
2 pathways of damage to the mitochondria
Apoptosis - by cytochrome c and other preapoptic proteins
Necrosis - mitochondrial membrane gets breached, inability to produce ATP
What does cytochrome c do?
Precursor for apoptosis
Increase of ca in the cell?
Very bad causes many things to go wrong
ROS (reactive oxygen species) impact what in the cell
Fatty acids
Proteins
DNA
Can ROS be expelled?
Yes by SOD
Glutathione peroxidase
Catalase (in peroxisomes)
Sequstration of free ionized iron and copper in ROS
Free ionized iron and copper can casue ROS and oxygen free radical production via Fenton reaction
What happens when there is a defect in membrane permeability?
Plasma membrane damage
mitochondrial membrane damage
lysosomal membrane
What happens when Bax or Bak gets oligomerizised or dimerized?
They lead to cytochrome c release after pore formation
Bcl-2 family proteins
Bax, Bak and Bad proteins increase mitochondrial membrane permeability which are called pro-apoptotic proteins
Bcl-2 and Bcl-x are inhibitors of these which they are anti-apoptotic proteins
When activated caspases active proteases what happens?
Degradation of cytoskeletal proteins
2 things inflammation is responsible for?
inflammation is responsible for eliminating infection
inflammation is responsible for repairing damages
What are the classical signs of acute inflammation (5)
- heat (warmth)
- redness (erythema)
- swelling (edema)
- pain
- loss of function
What happens inside of the capillary that can tell you there is inflammation (2)
- vascular changes
- cellular events
Functions of inflammation
- to improve the delivery of inflammatory cells to the injured/infected area tissue
- Vascular changes associated with inflammation
A) Changes in vascular diameter and flow that results in reduced
blood velocity
a)vasodilation
b)increased viscosity (thickness)
c)margination - when the leukocytes slow down and gives it
more chance to bind and help the site of inflammation
Functions of inflammation (part 2)
B. Increased vascular permeability
a) endothelial cells contraction/retraction leading to intercellular
gaps that leak fluid
b) direct endothelial injury
c) leukocyte dependent damage because of toxic mediators
released by leukocytes
d) increased fluid flow through endothelial cells is called (transcytosis) from vascular to tissues on the other side
What does transcytosis mean?
An increased fluid flow from vascular side to the tissues on the other side
What are 2 effects of vascular changes
- Release of transudate (small holes)
- Release of exudate (bigger holes / proteins can escape)
-> these events result in edema
What does the Sialyl-Lewis X modified glycoprotein bind to
P-selectin or E-selectin
What does the integrin on the leukocyte bind to?
Integrin ligand (ICAM-1)
What does PECAM-1 do?
Helps aid the leukocytes into the site of infection
What are the 4 receptors that lead to leukocyte activation?
GPCRs, Toll-like receptors, Cytokine receptors, Phagocytic receptor
What does LPS do when bound to toll-like receptor?
Casues the production of downstream mediators
What are the steps of phagocytosis?
- Recognition and attachment to the receptors
- Engulfment as the phagocyte zips up around the microbe
- Microbe becomes ingested and fuses with the lysosome to make a phagolysosome
What is the pH of the lysosome
Very acidic ~4
Full events through cellular inflammation
- migration and rolling (margination, rolling, p-selecting)
- Adhesion is mediated by Sialyl-Lewis glycoproteins and selectins
- firm adhesion (ICAM-1 and VCAM-1 help bind more tight)
- Transmigration (when the leukocyte goes through the vascular endothelial cells to the site of action)
- chemotaxis and activation (they keep releasing more chemokines to call more leukocytes to the affected area
- Phagocytosis (goes through the process of engulfing and fusing with the lysosome to degrade)
- Degranulation (When phagosome and lysosome fuse together and break down the contents)
- Phagocytosis stimulates an oxidative burst (results in OFR and ROS) They can make very strong agents which can break stuff down
- Proteins present in the lysosome also help destroy foreign bodies
(lysozyme, hydrolases and elastases, defensins
What are opsonins
key to a process called opsonization, they coat microbes and target them for phagocytosis
What does nitric oxide produce?
Arginine production
What inhibits phospholipase?
Steriods inhibit
What inhibits cyclooxyrgenase ?
COX-1 and COX-2 inhibitors like aspirin
What are COX1/2 inhibitors
Aspirin, ibuprofen, naproxen
What are the COX-2 inhibitors
Celebrex, vioxx (more cronic pain)
What does singular act as an agonist on?
It is a leukotriene receptor antagonist (causes vasoconstriction)
What do TNF/IL1 increase?
Endothelial effects, fibroblast effects, systemic effects, and leukocyte effects
Outcomes of acute inflammation
Can lead to chronic inflammation over time but most likely it gets resolved, can also lead to fibrosis which is loss of function and smaller capillaries
How long does chronic inflammation last?
Weeks to months to years
What differs in chronic inflammation than in acute inflammation?
Chronic inflammation has macrophages, lymphocytes, and plasma cells
How do we defend from pathogens?
Physical and chemical barriers , innate and adaptive immunity
Microbiome is what?
all of the bacteria in the intestine
How can pathogens get into the skin and cause infection?
Can enter through wounds, burns, cuts, foot sores ect
How can the skin defend against pathogens?
It has a dense ketatinized outer layer of skin
The outside layer has a low oH of 5.5
It has contents of fatty acid which inhibit micrbial growth
How does the respiratory tract defend against pathogens ?
Muscus, swallowing, cillia
Phagocytotic killing by alveolar macrophages
Secreted antibodies
How can pathogens get in the respiratory tracts
Express molecules to adhere to the respiratory tract (flu vaccine)
Defenses in the intentional tract
Acidic pH
Vicious mucus secretions
Lytic pancreatic enzymes and bile detergents
Antimicrobial peptides called defensins
IgA
Normal gut flora
How can pathogens break the intestional tract defenses and cause diseases
Bacteria can release exotoxins to damage the mucosa
Viruses can be resistant to bile and digestive enzymes
Fungo in immunocompromised hosts
Intentional protozoan rely on cysts for transmission
Intestinal helminths such as ascaris typically cause abstraction for the gut
The normal defenses in ingested pathogens include …..?
Frequent urination
Low pH in the vagina cause catabolism of glycogen in the normal epithelium by commensal lactobacilli
What are the ways that pathogens can get into the urogenital tract?
Hard to get male UTI’s because its longer than girls
Antibiotics can kill helpful female bacteria and make it more susceptible
Intercorse can break down some layers make it more susceptible to pathogens
What are the 4 ways microbes can evade the immune defense?
- Remaining inaccessible to the host immune system
- Constantly changing antigenic repertoires
- Can resist some antibodies and can resist phagocytosis
- inhibit the MHC expression which will ultimately keep the infected cells instead of getting rid of them
What are the 3 mechanisms of viral entry into host cells?
- Host-cell receptors for a particular virus
a) HIV : gp120 binds to CD4 and to the chemokine receptors CXCR4 or CCR5
b) Rhinovirus : binds to ICAM-1
c) SARS-CoV-2 : spike proteins/ACE2 receptor - Cell-type specific transcription factors that recognize viral enhancer and promoter sequences
- Physical barriers
What is the mechanism of viral injury?
Virus binds, viral genome replication and mRNA synthesis, viral protein synthesis, the viral proteins will then get expressed and is trying to assemble another particle that will spread to another cell
What are the mechanisms of viral injury?
- Lyse of host cells
- Immune cell-mediated killing
- Alteration of apoptosis pathways (also they can inhibit apoptosis which will keep the virus alive longer)
- Introduction of cell proliferation which will result in cancer
- Inhibition of host cell DNA, RNA or protein synthesis
- Damage to the plasma membrane
- Damage to cells involved in the antimicrobial defense, leading to secondary infections
Mechanisms of bacterial injury?
- The ability of bacteria to cause disease, depends on its ability to adhere to host cells, invade cells and tissues, deliver toxins to damage the cells
- Bacterial adherence to host cells
- Virulence of intracellular bacteria
- Bacterial endotoxin (has an LPS that is a major component of the outer cell wall of gram-negative bacteria
- Bacterial exotoxins, cause the damage themselves`
How can diphtheria toxin inhibit protein synthesis?
The toxin AB goes into the cell and once in an endosome A gets released and catalyzes ADP-ribose from NAD to EF-2 (the elongation factor) which inactivates the protein synthesis thereby killing it
What are parenchymal cells?
Functional cells of the organ (hepatocytes, myocytes, renal tubular cells)
What are stomal cells?
Cells that support the structure of organs (ECM, blood vessels, connective tissue)
Tissue regeneration is ?
Replacement of injured tissue with cells of the same type and function.
What is tissue repair ?
occurs when the extent or nature of damage cannot be reversed by regeneration alone
When theres acute injury what happens?
Regeneration of the tissue (normal function)
or
Repair, scar formation
What happens when there is persistent tissue damage?
Fibrosis (wont act the same again)
What are the 4 stages of healing after a tissue injury?
hemostasis (minutes)
inflammation (hours)
proliferation (days)
remodeling (weeks to months) still susceptible to injury but takes awhile
What do macrophages secrete in the stages of healing during tissue injury?
EGF epidermal growth factors
Complete injury healing require both ….?
proliferation and remodeling
What are the determinants of regeneration versus repair?
- the nature of cells injured
- the extent of injury
- the presence or absence of ongoing inflammation
- underlying diseases
What is primary intention wound management
A cut that gets a staple and heals up
What is secondary intention? (wound management)
There is inflammation that they let heal naturally but pack with gause and takes time
What is tertiary intention? (wound healing)
Over time after an infection they eventually close it up when the infection is gone
What drives proliferation?
Growth factors
Can you modulate EGF?
Yes, there are many potential drug targets for modulating EGF signaling, which leads to porliferation
What type of drug enhancer will you give someone to start proliferation
A drug that enhances EGF activity
What are some of the components and functions of the ECM (extracellular matrix)
ECM is a growth factor depot
ECM provides signals for proliferation
ECM is related to tissue shape as well as provides mechanical properties
ECM provides anchorage for cells through various interactions
ECM is related to adhesion and cell spreading
What are the growth factors that regulate fibrosis
PDGF
TGFb
FGF-2
What disease state can impair wound healing?
Diabetes
What is edema?
When there is excess fluid in tissues that can cause excessive swelling
What are the three key elements of shock?
Life threatening condition
circulatory failure
inadequate oxygenation
What are the 4 types of shock?
Distributive shock (vasodilation)
Hypovolemic shock (lose vascular volume)
Cardiogenic shock (wrong with the heart)
Obstructive shock (passage blocked)
What is the most common type of shock
Distributive shock (vasodilatory shock)
What causes distributive shock?
Sepsis #1 cause
Anaphylaxis
Neurogenic
What is septic shock?
An infection in the blood that results in organ disfunction / 25-50% mortality rate
What gram-negative bacteria mediates septic shock?
Endotoxin
What does adrenomedullin do?
Binds to receptor and tightens junctions causing less stuff to get through, it can induce vasodialation making the sepsis worse.
Intravasuclar space is good thing
Interstitial space is bad thing
What happens when you give an antibody that attaches to adrenomoedullin?
It stays in the intravascular space making it not able to move across to the interstitial space thereby not causing the sepsis to get worse
Causes of hypovolemic shock?
hemorrhage
sever burns
serve vomiting, diarrhea
How does hypovolemic start?
A loss of plasma or blood volume
What can cause a hemorrhage?
hypothermia
coagulopathy (losing coagulation factors)
acidosis
What casues cardiogenic shock?
myocardial infraction
ventricular arrhthmia
cardia myopathy (muscle weakens)
valvular disease (leaky valves)
What causes obstructive shock
Cardiac tamponade
pulmonary embolism
pnemothorax (air not in the heart causing pressure)
What can you physically see when someone is going through one of the 4 shocks?
low blood pressure
high heart rate
What is edema
edema is an accumulation of fluid in the interstitial space of body tissues (subcutaneous / legs, pulmonary, cerebral)
What is hydrostatic pressure?
Pushes fluid out of vascular space
What is colloid osmotic pressure?
Moves fluid in to vascular space and out of the interstitial space
What is transudate?
Protein poor
What is exudate?
Protein rich
What are the 3 ways drugs can cause edema?
Lymphatic drainage disruption
Increased capillary hydrostatic pressure
Increased capillary permeability
