Quiz 1 - Module 1 Flashcards
Which of the following cells do not normally circulate in the blood?
Neutrophils
Monocytes
Eosinophils
Mast cells
Mast cells
An increase in cell size resulting in an increase in the size of the organ is an example of?
Hyperplasia
Atrophy
Hypertrophy
Apoptosis
Hypertrophy
Which of these is a physiological hyperplasia
Skin warts
excesssive endometrial hyperplasia
englarged prostate
liver regeneration
liver regeneration
Identify the leading causes of mortality inter- /nationally, and diseases affecting First Nations and non-Indigenous Australians
Coronary Heart Disease Cancer HIV/AIDS Respiratory conditions ** these are all preventable by lifestyle changes
Stroke RHD DM CKD IHD
Provide examples of ways in which cells detect and adapt to stress
If a cells stable ‘homeostasis’ environment becomes stressed it results in ‘adaption’ - reversible changes in structure / function = survival
- Hypertrophy, hyperplasia, atrophy, metaplasia
If stress is too great it can lead to cell injury. Irreversible stress causes cell death by 3 mechanisms
- Apoptosis (programmed), necrosis (mortification/death), autophagy (eat oneself)
What are the two cellular responses to stress
Acute = physiological
Chronic/severe = pathological
Chronic /severe stress cause cell death = apoptosis or necrosis
Necrosis = reversible/irreversible, leading to cell swelling / cell damage + then inflammation
Provide examples of physiological/pathological adaptation
Physiologic : Hyperplasia
- Hormonal - when needed (breast tissue, puberty, pregnancy)
- compensatory - damage / resection (liver regeneration
Pathologic : Hyperplasia
- excess hormone / growth factors (abnormal menstural bleeding, viral infections, benign prostatic hyperplasia (excess androgen)
- Mechanisms - growth factors stimulate cell signalling resulting in cellular proliferation
Describe how nuclei and proteins are identified in microscopic slides (histology)
By metaplasia : transformation of one cell type to another
e.g. columnar to squamous epithelium
Compare the histologic presentation of necrosis and apoptosis
Cell damage = necrosis
During initial stages of ischemia, lack of O2 leads to ATP depletion, itnracellular Na+ accumulation causes osmotic cell swelling (reversible), before memrbane rupture
Describe types of necrosis
Coagulative
Coagulative Necrosis
- Caused by coagulation causing ischemia
- tissue swelling, loss of nuclei
- infarct is firm to touch, blocks proteolysis (denaturation of proteins + enzymes)
- all organ by brain
What are the four types of necrosis
Coagulative
Liquifactive
Caseous
Gangrenous
Describe types of necrosis
Liquifactive
Hypoxia (brain)
Bacterial
Fungal infections
Digestion of dead cells
Describe types of necrosis
Gangrenous
Affects peripheral limbs, lack of oxygen, diabetes, PAD
Describe types of necrosis
Caseous
typical in tuberculosis, inflammation, dead cells, infiltrated leukocytes
What are the mechanisms of cell injury / death
Mitochondrial damage (leakage of pro-apoptotic proteins)
Decreased ATP (multiple downstream effects)
Entry of Ca2+, increased ROS (damage to lipids, proteins, DNA), protein misfolding and DNA damage
Membrane damage (loss of cellular components, enzyme digestion of cellular components)
Understand specific pathways/ molecules involved in apoptosis
‘Programmed cell death’
- stimulated by toxins, ischemia, radiation
Physiological Apoptosis
- embryogenesis - death of specific cell type at defined time during development
- cell loss in proliferating cell populations - immature lypmphocytes in bone marrow
Pathologic apoptosis
- DNA damage - radiation, cytoxic anticancer drugs
- accumulation of misfolded proteins - DNA mutation, coding for proteins (neuro-degerative disorders)
- cell death in certain disorders (HIV, Hepatitis)
Describe morphological and biochemical changes within cells during apoptosis
Morphological
- cell shrinkage
chromatin condesnation (DNA condense)
- membrane blebbing, small cell fragments containing organelles
- phagocytosis of apoptotic bodies by macrophages
Biochemical
- DNA and protein breakdown
- Membrane alterations, phagocytosis
- outer cell membrane recognised by phagocyte receptors
- experimentally revealed using the annexin V antibody
What is necrosis
Permeation of cell membrane
Inflammatory response
What is apoptosis
Programmed cell death
- DNA damage
No inflammatory response
What stresses are mitochondrial sensitive to?
Increased calcium
ROS
Decreased O2
Toxins
What are antioxidants?
Simple molecules that block or inactivate free radicals
- Vitamin A, C, E, glutathione, bilirubin
Name 2 clinical examples of cell damage and what occurs
Ischemia and Hypoxaemic injury
- ischemia decreased O2 delivery to tissues from arterial blockage
- decreased venous drainage; decreased arterial inflow causing ischemia
- hypoxia decreased oxygen in blood
- primary cause of cell deaht -> ATP depletion
Name 2 clinical examples of cell damage
Ischemia / reperfusion
Chemical / toxin injury
Define ischaemia / reperfusion
- Restoration of blood flow futher exacerbates injury
- causes new and distinct damaging processes (decreased O2)
- increased ROS from mitochondrial damage
- inflammation caused by macrophages
Define chemical/ toxin injury
- prescribed drugs, pollutants, food born toxins
- target liver
- 2 major mechanisms
1. direct cell injury
2. secondary metabolism - drugs metabolised, products are toxic / deplete cells of nutrients
Describe the mechanisms of apoptosis
- too much apoptosis = neurodegeneration
- too little apoptosis = cancer
- initiation
- activation of caspases by
- instrinsic pathway (mitochondrial)
- extrinsic pathway (death receptor)
- activation of caspases by
- execution
- degradation of cell components
What is autophagic cell death?
Autophagy = eat oneself
- self digestion of cells during starvation
- merge with lysosoem = eventual cell death = NS + muscular diseases
What happens when apoptosis increases/ deacreases?
Increased apoptosis (protein accumulation) = neurodegeneration = decreased (p53 mutation) = cancer
Describe the different intracellular accumulations that resilt in cell death?
2 types
- normal cellular constituents (water, lipids, proteins)
- abnormal substances, ifnectious agents, abnormal synthesis/metabolism
What are the 4 main causes of accumulations?
- Abnormal metabolism
- Defect in protein folding, transport
- Lack of enzyme
- Ingestion of indigestable materials
Describe steatosis?
accumulation of triglycerides
- liver, msucle, heart, kidneys,
Aetiology - toxins (alcohol), protein malnutrition, diabetes, obesity
- causes - lipid accumulation (excess alcohol), decreased metabolism (hypoxia), cell death, inflammation = organ failure = cancer
What is inflammation?
- biological responses aimed at destroying invading pathogens / eliminating damaged cells
- w/o wounds wouldn’t heal, infectious would overwhelm homeostasis
- dysregulations = chronic diseases
- composed of blood vessels + leukocytes
What is the difference between acute vs chronic inflammation?
Acute
- minutes, hours, days
- leukocytes (neutrophil), infiltration, oedema
Chronic
- can follow acute, lasts for months
- infiltration of macrophages, lymphocytes, causes fibrosis, tissue destruction
What are clinical manifestations?
- vasodilation - histamine (rubor)
- heat (calor) - dilation of artioles + capillary beds
- icnreased vascular permeability (venules)
- oedema (tumour; oncotic pressure)
- local pain (dolar) induced by prostaglandin, cytokine release
What is the blood vessel involvement in inflammation?
acute inflammation delivers leukocytes to area of infection
- increased erythema, calor
- extravation + deposition of plasma fluid + proteins
- emigration / accumulation of leukocytes
What are some stimulis for inflammation?
Infectious material
- bacterial, viruses, parasitic
- recognised by leukocytes
- stimulates inflammatory mediators
Tissue necrosis
- MI, trauma, hypoxia
- releases cell contents
Foreign bodies (splinters) - introduce microbes, cause cell necrosis
What are the two blood vessel reactions - acute inflammation
Transudate
- movement of fluid exept proteins, no cellular material, low specific gravity into interstitial space
Exudate
- escape of fluids / proteins, cellular debris, high specific gravity from blood –> IF (inflammation)
- **both can cause oedema
- ** Pus = purlent exudate = leukocytes, microbes, debris
What does flow and calibre mean (blood vessel reactions)
Vasodilation - early, caused by histamine _ nitric oxide release e.g. transient ischemia
- Also causes increased permeability of microvasuclature
- decreased red blood flow, increased viscosity, congestion
- encourages leukocytes to accumulate upon endothelium, migrate from circulation into tissue
- decreased red blood flow, increased viscosity, congestion
Describe vascular permeability
A. Normal B. Retraction of endotheilial cells C. Endothelial injury D. Leukocute mediated cascilar injury E. Icnreased transcytosis
Describe the role of leukocytes and inflammation
Role of inflammation
- Deliver phagocytic leukocytes to area
- destroy invading pathogens / nectroic cells
- can result in destruction of healthy cells
- secretion of growth factors for repair
- Recruitment of leukocytes
- extravation (vessel - IF) - Migration across endothelial + vessel wall
- Migration in the tissues toward chemotactic stimulus (chemotaxis)
