FINAL EXAM REVISIONS - LEARNING OBJECTIVE Flashcards
What does Haematoxylin stain? What Colour?
Stains the Nucleus (Nuclei and Lymph node) dark blue or Purple
What does Eosin stain? What Colour?
Stains the Cytoplasm (Proteins - Muscle or cytoplasm with little nucleus) pink
Define Cellular Differentiation
- Features in cell that show it has a function and structure
- It is a specialised Cell
What is a specialised Cell?
A Nucleus that contains microvilli attached
What is an undifferentiated cell?
- A cell that does not have a function
- It is an Unspecialised cell
What is an unspecialised cell
- It is a Stem Cell
- Just a Nucleus
What is a Gastrula made up of?
Ectoderm, Germ Cells, Mesoderm, Endoderm
Does a change in Environment cause a change in a cell?
Yes, in each cell there is DNA and specific strands can be turned on and turned off based on the surrounding environment
Environment is a determinant in what a cell can become.
Cell considered Epithelial?
Skin Cells GIT cells Reproductive Cells Urinary Tract Cells Lining of Exocrine ducts Liver Cells Kidney Cells Respiratory cells Pancreas Cells Glandular Epithelial Cells
Types of Epithelial Cells? There’s 7…
Simple Squamous Stratified Squamous Simple Cuboidal Simple Columnar Pseudo Stratified Transitional Stratified Cuboidal/Columnar
Feature of a Simple Squamous Epithelium:
- Single Layer
- Cytoplasm usually appears thinner than Nuclei
- Allows gases, ions and small molecules to pass through
What are the 3 types of cells:
Labile
Stable
Permanent
What are Labile Cells
Continuously Dividing
Epithelial
Haemopoietic Stem Cells
What are Stable Cells
Divide only when required - growing tissue back
Epithelial
Smooth Muscle Cells, Fibroblasts and endothelial Cells
What are Permanent Cells?
Non-Dividing Cells
Cardiac Cells
Skeletal Myocytes
CNS Neurons
What is proliferation? Explain the process
The rapid division of a cell
DNA is unwined and replicated during the cell cycle if stimulated - G0 is cell cycle arrest - stable cells
Stages of the Cell Cycle
During the cell cycle, cells become labile
Stages: G1, S, G2, Mitosis, Cytokinesis
What do tissues need?
Nerve Innovation Blood and Lymphatic Supply and removal: - Gases, Hormones and Growth Factors Defence against invasions: - Skin/Epidermis (fat) - GIT - Urogenital - Respiratory
What do Cells Need?
Functional Plasma Membrane (Skin) Ability to make RNA and Proteins Ability to Copy and repair DNA Functional cytoskeletal proteins Energy (ATP) Antioxidant Defences Ability to remove waste including proteins Ability to repair or destroy redundant and damaged organelles The correct temperature, pH, etc.
How do cells communicate?
Through distant cells using chemicals released into the blood such as hormones
Through Neighbouring cells and connecting tissue (Acting in a paracrine matter)
- Epithelial Cells like to be attached to their neighbours and membranes beneath them
What is a Paracrine process?
Communication with neighbouring cells directly
What is an Autocrine process?
The cell communicates with itself
What is an Endocrine process?
The cells communicates over distance through blood
Mitochondria
Surrounded by a double membrane Generate ATP Full of Oxidative Enzymes Induces cell death Possibly drives differentiation
What are Oxidative Enzymes?
A Bi-product of ATP that prevent the mitochondria from stealing electrons and damaging the lipid
Lysosomes? Types?
Waste Disposal Membrane-Bound Digestive Organelles Primary Lysosomes Secondary Lysosomes: - Heterophagosomes - Autophagosomes
How does the cell membrane work with Lysosomes
It fuses with a lysosome containting acid and breaks down constituents, thus removing waste
What is Autophagy? How does it work?
Self Eating - Nutrient Depletion - The cells shrinks itself by eating a part of itself
Reduction in cell Size
Mitochondria and Autophagy
If the mitochondria is damaged by free-radicals and cannot repair, it will need removal. The cell designates a section of the cytoplasm containing the dodgy mitochondria for removal.
Define Physiology:
Scientific Study of the function of living things
Define Pathology:
Scientific Study of Disease
Define Active:
Requiring Energy
Define Passive:
Does not require energy
Define Aerobic:
Done with oxygen
Define Anaerobic:
Done without Oxygen
Define Hypoxia:
Lack of Oxygen
Define Ischaemia:
Lack of Blood Supply - “Distruption”
Define Reperfusion:
Restoration of blood following a period of Ischaemia
Define Acute:
Sudden Onset
Sudden Severe
Define Chronic:
Long Duration of Severeness
What can cause Cell Stress/Injury:
Mutation: Tumour, impaired Function
Cell Death: Apoptosis, Necrosis
Adaptation: Autophagy, Hypertrophy, Hyperplasia, Metaplasia
How does cell stress occur? Flow Chart…
Normal Cell - STRESS - Adaptation - INABILITY TO ADAPT - Cell Injury - SEVERE, PROGRESSIVE - Irreversible Injury - Cell Death (Necrosis, Apoptosis)
Normal Cell - INJURIOUS STIMULUS - Cell Injury - SEVERE, PROGRESSIVE - Irreversible Injury - Cell Death (Necrosis, Apoptosis)
If a normal cell that undergoes cell injury is only mild and transient that reversibility can occur returning the cell back to normal.
What does Stress lead to?
Stress –> Cell Death = Apoptosis and Necrosis
Stress can stimulate either form of death depending upon the duration and severity of the application and the resources of the cell
Define Apoptosis:
Programmed cell death, Cell Suicide
Takes itself away from other organelles and kills itself - Active dismantling
Phagocytosis (removal) of apoptic bodies using Macrophages and Neighbouring cells
No inflammation or scarring
Decrease in cell number
Define Necrosis:
Sudden Death
Negatives with Necrosis
Doesn’t have time to move away from neighbouring cells
Neighbouring cells undergo Necrosis
Stimulation of Acute Inflammation
Loss and reduction in tissue function - Scarring, Calcification, Death
Define Infarction:
Area of Necrotic Tissue
Physiological jobs of Apoptosis:
- Embyronic Development
- Tissue homeostasis
- Removal of redundant cells
- Crucial for immune function
- Immune-mediated Killing
Pathological jobs of Apoptosis:
- Pathological Atrophy
- Transplant Rejection
- Autoimmune Diseases
- Some infections
- Anti-cancer treatment (Targets dividing cells)
Apoptosis VS Necrosis?
- Apoptosis occurs in physiology and pathology. Necrosis is pathological
- Apoptosis is Active. Necrosis is Passive
- A single cell can die from Apoptosis. Neighbouring cells die from necrosis
- Apoptosis does not stimulate Inflammation. Necrosis stimulates inflammation
What causes Adaptation?
Increased Workload or demand
Altered Environment
What is Tissue Atrophy
The absence of nourishment, development or growth at THE TISSUE LEVEL
A reduction in size and cell number of individual cells in a tissue/organ undergoing a combination of AUTOPHAGY and APOPTOSIS or just APOPTOSIS in ‘old’ cells
Not Reversible - occurs in permanent tissue
Mitochondria and Ageing
As we age, the mitochondria produces less anti-oxidant defences and more oxidative enzymes - more susceptible to injuries
As we age, the mitochondria becomes weaker and more damaged as free radicals increase as ATP decreases
What are Free Radicals?
Highly reactive elements that can kill the mitochondria and cause damage to cells
What happens to the mitochondria usually once it is damaged by free radicals? What about with ageing?
Usually, it would undergo autophagy where is isolates itself, fuses with a lysosome and degrades until it becomes a ‘recycling of metabolites’
When we age, the cells are too old to isolate and lose ability to undergo autophagy. This causes the mitochondria to release free radicals and damage the surrounding cells as well
What effect does ageing have on cells and organs?
A decreased ability to undergo Autophagy - Cells atrophy with age
Healthy Cell - Cellular response to stress (Low, Moderate and Sudden Severe Stress)
Healthy Cell –> Adapt Autophagy –> Apoptosis –> Necrosis
Old Cell - Cellular response to stress (Low, Moderate and Sudden Severe Stress)
Old Cell –> Apoptosis –> Necrosis
Physiological and Pathological examples of Tissue Atrophy
Physiological: INVOLUTION (Shrinkage of tissue when inactive)
Pathological: GRADUAL DECREASE IN CELL SIZE AND NUMBER
Atrophy vs Infarction
Atrophy: - Caused by Gradual Stress - Involves Apoptosis (Decrease in cell number) - Involves Autophagy (Decrease in cell size) Infarction: - Caused by Sudden Severe Stress - Ischaemia - Haemorrhagic
What is Metaplasia?
Reversible
The change from one normal/well-differentiated cell type to another normal well-differentiated cell type usually because of a change in environment
Increase risk in mutation = Increase in Cancer
- Example: Smoking causes the conductive region of the airways to go from pseudostratified epithelium with goblet cells to stratified squamous epithelial cells due to the change to a harsher environment due to carcinogens
Define Hyperplasia:
Increased number of cells
Stabile or Labile cells can undergo hyperplasia and cause an abnormal increased rate of cell division (failure of apoptosis in a labile tissue (Whats dying isnt being removed))
Define Hypertrophy:
Increase in cell size – Enlarged Organ
Connective Tissue Type:
Myocytes - Muscle Cells Fibroblasts Collagen Fat Endothelium (lining of blood vessels) Cartilage (Chondrocytes) Bone (Osteoblasts, Osteocytes)
Are Skeletal Muscle fibers permanent?
Yes, but they are able to repair not replaced
ALSO:
- Contain possible 100s of nuclei in each cell
Are Cardiac Myocytes Permanent?
Yes, and there is no repair
ALSO:
- Individual cells with single, central nuclei
Are smooth Muscle permantent?
No, they are stable cells but can divide when necessary
What are Fibroblasts?
Stable cells secreting collagen
What is Collagen
A long stringy contractible protein - Stable cell
What is fat?
Adipocytes - large cells with a cytoplasm full of fat
Nucleus against the edge
Are the endothelium, cartilage and bone permanent cells?
No they are stable cells
Function of the Epithelium:
Mechanical Stress Chemical Stress Secretion - Lubrication, Digestion, Excretion Absorption Transport
What are Glandular Epithelial Cells?
Secretory cells
Endocrine - Secrete into blood acting on receptor in distant site
Exocrine - Secretion into lumes or duct
Stratified Squamous Epithelium:
Basal cuboidal-like cells that matures as it migrates towards the surface
At some sites, a keratinised upper layeer reduces absorption but increases strength
Lines surfaces exposed to abrasion, friction, physical stress:
- Skin, oral cavity, pharynx, oesophagus, anal canal, outer cervix (ectocervix), Vagina
Labile cells
Simple Cuboidal Epithelium:
Tall and wide Lines protected surfaces: - Exocrine glandular ducts - Collecting tubules of the kidney - Outer surface of ovary Labile or Stable cells
Simple Columnar Epithelium:
Line surfaces involved in secretion and absorption
Sometimes microvilli are present to increase the surface area of the absorptive membrane or cilia to aid movement across the surface
Pseudo Stratified:
Located in upper respiratory tract and male reproductive system
Appears as stratified but it is simple single layer
Stable Cells
Transitional Epithelium:
Restricted to Urinary System - Renal, Calyxes, Ureters, Bladder and Urethra
Allow stretch and retraction that look columna when relaxed but cuboidal when stretched
Stratified Cuboidal:
Lines mammary glands, part of the cohchlea, germ cells of the seminiferous tubules and granulosa cells of the ovarian follicles
Straified Cuboidal/Columnar:
Rare
Some large ducts are lines by columnar on top of cuboidal
Other Tissues:
Aren’t considered connective or epithelial:
- Mesothelial cells
- Melanocytes
- Neural Tissue
- —–Meninges
- —–Glial Cells
- —–Neurones
- Germ Cells
- Lymphoid tissue and cells
- Bone marrow and haemopoietic cells
- RBC’s
- Neutrophils
- Macrophages
Define tumour:
Denotes Swelling
Define Benign Tumour
Friendly, causes no harm
Define Malignant Tumour
Potentially Fatal
Cancer
Can Benign Tumours be cancers?
NO
How do mutations occur?
Cells that are dividing have the greatest chance of sustaining a mutation
- Epithelial cells are capable of dividing and some continuously divide
- Epithelial cells are on the front line
Epithelial cancers increase in incidence as we age
It takes many mutations to create a cancer cell and we acquire mutations over time
More than 90% of cancers are Carcinomas
Non-lethal Genetic damage
What happens to cells if there is no adaption or it fails to adapt?
Dysplasia
What is Dysplasia?
A pre-cancerous exchange
Usually the immune system destroys these, but it can accumulate with age
The Genotype and phenotype are abnormal
What are Mutagens?
A substance that can cause genetic mutation
May act directly to cause damage or may do so through increasing oxidant production or reduction or reducing anti-oxidant defences causing an increase in free radicals
What causes mutagens?
Exposure to carcinogens UV Alcohol Smoking Obesity Genetics Viruses Some Chronic Inflammatory conditions - Not necessary but can happen
What are four classes of normal regulatory genes that are principle targets of genetic damage?
1- Growth promoting onoco-genes
2- Growth Inhibiting Tumour Suppressing genes
3- Genes that regulate Apoptosis
4- DNA repair genes
What is the molecular basis of cancer? “The essential alterations for malignant transformation?”
- Self-sufficiency in growth signals
- Insensitivity to growth-inhibitory signals
- Evasion of Apoptosis
- Defects in DNA repair
- Limitless replicative potential
- Sustained Angiogenesis
- Ability to invade and metastasize
- Predilection for glycolysis even in the presence of oxygen
Define Self-sufficiency in growth signals
Proliferation without any external stimuli
Define Insensitivity to growth-inhibitory signals
Ignore signals sent out by sells to stop growth
Define Evasion of Apoptosis
When DNA damage occurs, the cells is mutated enough that the apoptopic pathway has been turned off, and cells arent removed
Define Defects in DNA repair
DNA doesnt scan cells for mutations or mistakes when formed, mutations accumulate
Define Limitless replicative potential
Immortal, continuous division of cells with genetic errors
Define Sustained Angiogenesis
Formation of new blood vessels to support mutation
Benign - Neat Blood vessel formation
Malignant - Messy and out of order blood vessel formation
Define Ability to invade and metastasize
Mutated Cells can pass the basement membrane and enter blood vessel and migrate to a different site to invade and mutate more cells
Define Predilection for glycolysis even in the presence of oxygen
Cancer Cells choose not to us oxygen but rather use glucose
Aerobic glycolysis - Warburg Effect
What is a cancer cell called when it hasnt passed the basement membrane
Carcinoma in-situ
How does a cell accumulate mutations?
Normal Cell undergoes DNA Damage - hopefully repairs, if it doesnt, apoptosis, but if that fails too then - Genetic Instability in the cell cycle, Unregulated division, inability to undergo further apoptosis, Invasive Cancer, Metastisis
Benign VS Malignant
Benign:
- NEVER metastisize
- Encapsulated
- Homogenous - uniformity between cells (Same appearance)
- Well Differentiated
- Cytoplasmic ratio is close to normal
- Slow Growing
Malignant:
- POTENTIALLY metastisise
- Infiltrative growth
- Heterogeneous - Lack uniformity (Different Appearance)
- Well/poorly-differentiated or undifferentiated
- Increased nuclear to cytoplasmic ratio
- Fast Growing
3 routes of metastasis?
1- Blood (haematogenous)
2- Lymphatics (vessels & Nodes)
3- Direct Seeding (through/within body cavities)
What is the most common site of metastatic neoplasms?
Will try to travel through the capillary bed all the way to the secondary location
Secondaries: Lung then Liver
What is the nomenclature of BENIGN connective tissue called?
Fibroma - Fibroblasts Leiomyoma - Smooth Muscle Chondroma - Cartilage Osteoma - Bone Lipoma -Fat Haemangioma - Endothelial lining of blood vessels
What is a MALIGNANT tumour derived from connective tissue?
SARCOMA Suffix
“sarc” = Malignant from connective tissue origin
SUPER RARE - Less than 10% for these
Nomenclature of epithelial BENIGN tumours?
Papilloma - Finger like projections
Adenoma - Glandular cells
Cystadenoma - Fluid-filled sac
What is a MALIGNANT tumour derived from epithelial tissue called?
CARCINOMA suffix
“Carc” - Malignant and Epithelial cell of origin
More then 90% of cancer - Proliferation and Stress
What type of tumour do other tissues form?
Malignant tumours
What is a meningioma?
It is a benign tumour located in the brain and can kill
What is a Mature Ovarian Teretoma?
It is a Benign dermoid cysts that is from a germ cell and isn’t fertilised but can give rise to a baby or parts of baby - hair, teeth, etc.
Monstrous Growth
What is a Testicular Tumour?
An immature Teratoma
Seminoma
Other types of Maligant tumours?
Melanoma Leukaemia Lymphoma Mesothelioma Glioma Testicular Tumour Blastoma
What is a Blastoma
Never a normal cell to begin with - during embryo genesis it got mutated.
Different types of pathogenesis:
Normal Cell - Multiple mutations - Cancer (NOT BENIGN)
Normal Cell - Multiple mutations - Benign Tumour
Normal Cell - Multiple mutations - Benign Tumour - Further mutations - Cancer (NOT STABLE)
Normal Cell - Sustained Stress- Metaplasia - Multiple Mutations - Dysplasia - Further Mutations - Cancer
What is Melanoma?
Number 1 Cancer in Australia
Can be Caught in dysplastic stage before metastasis
Dont need much to become aggressive - already motile
Involve:
- Eyes
- Mucus Membrane
- Skin
NOT JUST SKIN CANCER
Pathogenesis of Melanoma?
Normal Cell - Multiple mutations - Cancer (NOT BENIGN)
What is Mesothelioma?
Very Aggressive Very rare Due to radiation exposure Asbestos On pleural lining CARCINOGENS can cause
Pathogenesis of Mesothelioma?
Normal Cell - Multiple mutations - Cancer (NOT BENIGN)
Pathogenesis of Ovarian Teratoma and Leiomyoma?
Normal Cell - Multiple mutations - Benign Tumour
Pathogenesis of Colon Cancer?
Normal Cell - Multiple mutations - Benign Tumour - Further mutations - Cancer (NOT STABLE)
Pathogenesis of Lung Cancer?
Normal Cell - Sustained Stress- Metaplasia - Multiple Mutations - Dysplasia - Further Mutations - Cancer
Stress: Carcinogen exposure
Pathogenesis for female reproductive cancer? How does it occur?
Normal Cell - Sustained Stress- Metaplasia - Multiple Mutations - Dysplasia - Further Mutations - Cancer
During Menstruation, cells in the endocervical canal are pushed out into a different environment that has a higher pH (Ectocervix) - Forced to adapt and become stratified to handle environment, can get mutations whilst adpating.
Grading VS Staging:
Grading:
- Nature of the cancer and aggressiveness
- 1 to 4, indicating 4 the worst prognosis
- Differentiation
- Number of mitoses dividing cells
- Varies depending on the cancer type
Staging:
- TNM system - talks about characteristics of tumour
- T1-T4 = Tumour size
- N0-N3 = Number of lymph nodes that are cancerous
- M0-M1 = Metastasis or not
Can Cancer be cured?
Many ‘early’ caught cancers can be however, 30% of patients have metastases at diagnosis
5 year survival rate
Cure or remission (partial/total)
Signs and Symptoms of Cancer?
Fat and Muscle Loss
Paraneoplastic Syndrome
Horomone, blood and mucous changes
Treatments of Cancer?
Surgery Radiotherapy Chemotherapy Hormone therapy Immunotherapy Hyperthermia
Treatment affects on host?
Healthy Cells lost - epithelial, immune
Mutation in health cells - Mesothelial, Lymphoid
Scars, Radiation Burns
Types of micro-organisms?
Parasites Yeast & Fungi Bacteria Viruses Prions
What is an Innate Defence system?
A defence system in the immune system that the body is born with
It has the same response every time no matter the damage
What is an Acquired Defence System?
A defence system in the immune system that the body adapts to.
It learns from past viruses and creates an army to to attack in the future - its specific to the virus
Involves Lymphocytes
Innate vs Acquired?
INNATE:
- Fast Response
- Non Specific
- Germline encoded
- Celullar response: Neutrophils, Macrophages, Natural Killer Cells
ACQUIRED:
- Slow Response
- Able to differentiate between lots of targets
- Learns and remembers
- Has a “memory”
- Cellular Response: T Cells and B cells
- Humoral: Antibodies
What is the function of a T Cell?
Activation of B cells and cytotoxic T cells
Travel to site and bind to the antigen
What is the function of a B Cell?
Matures into a plasma cells and produces antibodies which are released into the blood and bind to the antigen
Signal Destruction
What do the clinical manifestations of infections depend upon?
1- The host and principally the host response to the infection
2- Site of infection
3- Characteristics of the organism principally the intrinsic virulence of the organism
Define Virulence
The ability of power of a microorganism to cause disease
Low? No destruction unless immune compromised
What are Virulence Mechanisms?
Factors inherent to the organism, encoded at the molecular or gene level
Helps establish the infection causing the disease
What do these Virulence mechanisms involve?
Overcoming Defences
Damaging host cells
Altering host cells and/or cytokine production
Adhesive/invasive factors, capsules, slime, fimbbriae, pili, enzymes
Toxins (exotoxins, endotoxins, enterotoxins)
Cause damage and impair host defence
What are Sterile body sites?
Areas with NO microorganisms:
- Brain and CSF
- Blood
- Bone and Marrow
- Lower respiratory tract
- Upper urogenital - Male and female reproductive system
- Stomach
What are Non-Sterile body sites?
Areas with microorganisms:
- Skin
- GIT
- Upper Respiratory - Oral Cavity and Larynx
- Lower urogenital - Female Reproductive System (Ectocervix and vagina should have microorganisms)
What are Leukocytes?
White blood Cells
Cellular Components of Leukocytes:
Granulocytes and Agranulocyes
What are Granulocytes?
Destroy large bacteria by throwing chemical substances at microorganisms. Release granules Involve: - Neutrophils - phagocytes - Eosinophils - Basophils
What are Aganulocytes?
Involve:
- Lymphcytes
- Monocytes
What happens to Monocytes when they mature?
When a monocytes is activated and calledupon to a specific site, it matures and becomes a macrophage
Define Macrophage:
A immune cells that eats large cells that are dead
Has a long life span
Define Interstitial Fluid:
Fluid between cells
Define Oedema:
Increase in Interstitial flue causing a fluid build up in cavities and tissues
High-protein Oedema Vs Low Protein Oedema:
High-protein oedema:
- Water and Plasma proteins are leaking into tissue - Exudate
Low-protein Oedema:
- No plasma change but water is being pushed out -Transudate
Define Hyperaemia:
The Increase in blood flow to an area
Occurs actively
Vasodilation and increase in permeability causing oedema
How is hyperaemia impacted during acute inflammation?
Chemical mediators are released and induce mudcle in vessel to relax - causing it to become engorged in blood
Define Congestion:
Increase and accumulation in blood flow
Occurs passively
Usually not in arterial circuit but in venous circuit
What happens if the left side of the heart is congested?
Lungs become congested
What happens if the right side of the heart is congested?
Whole body in the venous system becomes congested
Define Exudate:
Inflammatory extra vascular fluid with high protein - High-protein Oedema
Define Transudate:
Extravascular fluid with low protein concentration - Low-protein Oedema
usually not caused by inflammation but by other things
Define Pus:
Purulent inflammatory exudate that is high in neutrophils, cell debris and sometimes pyogenic organisms
How does Transudate form:
Congestion increases hydrostatic pressure causing venous flow obstruction. The fluid leaks and goes into tissue to produce transudate making it harder to breathe. There is no change in colloidal osmotic pressure
How does Exudate form:
An increase in hydrostatic pressure causing venous flow obstruction allows the leakage of fluid.
A decrease in colloidal pressure causing a decrease in protein synthesis makes the endothelial more permeable allowing protein leakage.
Define inflammation:
No microorganism involved - just a disruption in blood supply - infarction due to necrosis
The body’s general response to injury and infection
The pattern of events is similar irrespective of the cause or its location
Types of inflammation:
Acute and Chronic
Define Acute inflammation:
The start of repair although it can lead to further injury
Nomenclature of inflammation
Suffix - “itis”
- DermatITIS
- PancreatITIS
- MeningITIS
- EncephalITIS
- BronchITIS
- TonsillITIS
- GastrITIS
- HepatITIS
- NephrITIS
What are the indicators of Acute Inflammation? How are they caused?
- Heat –> Hyperaemia
- Redness –> Hyperaemia
- Swelling –> Oedema due to Hyperaemia and increase permeability
- Pain –> Stretch receptors and chemical mediators
- Loss of function –> Swelling and Pain
“He Read Stories of Pain and Loss”
Define Chemotaxis:
The movement or locomotion according to a chemical gradient - Similar to metastasis
Define Chemokine:
Agent that induces chemotaxis
Define cytokine:
Hormone of the immune system
What is the vascular response to acute inflammation?
Release of soluble mediators from necrotic cells, infectious/foreign agents, nearby cells and plasma
- Dilation and Hyperaemia
- Extravasation of fluid and proteins (Oedema - exudate)
- Leukocyte…Neutrophil recruitment and activation
“Hyperaemia, Oedema, Neutrophil”
Cellular components of acute inflammation
Neutrophil
Monocyte which matures into a macrophage
What is extravasion?
Requires and intact vasculature
- Margination
- Rolling
- Adhesion
- Diapedesis
- Migration
What is Phagocytosis?
Taking up of dead tissue
- Recognition and attachment
- Engulfment
- Killing and Degredation
Aims of acute inflammation?
Dilute, Destroy and Clean up
If a stimulus was Necrosis and infection, what is the response?
Release of chemical mediators producing a vascular and cellular response.
The Vascular Response consists of Hyeraemia and Oedema
The cellular response involves the leukocyte activation and recruitment of Neutrophils and monocytes/Macrophages
Aims of Chronic Inflammation?
Wall-Off and Contain
What are the General Features of Acute inflammation
Early onset (secs –mins)
Short duration (mins – days)
Involves fluid exudation (oedema) & neutrophil emigration
May result in resolution or organisation
Define Resolution
Healing without scarring, restoration of structure and function
Possible following acute inflammation
Not possible in permanent cells
Depends on tissue type, extent of injury, presence of factors that can impair repair - infection, nutrition, etc.
Define organisation
Healing by scarring/fibrosis
Inevitable following chronic inflammation
Possible following acute inflammation, depends on tissue type, extent of injury, presence of factors that can impair repair - infection, nutrition, etc.
What are the outcomes of Acute inflammation
- Resolution (Healing no scar)
- Organisation (Healing with scar tissue)
- Chronic Inflammation - Worst Case Scenario
What is the scar tissue made up of?
Prior to maturation, scar tissue is composed of granulation tissue
Granulation tissue:
- Macrophages
- Fibroblasts/Myofibroblasts
- Angiogenesis
Mature scar is made up of collagen fibre proteins
What happens to collagen over time?
It contracts
What does each component of granulation tissue provide?
- Macrophages - Remove any debris
- Fibroblasts - secrete collagen
- Angiogenesis - provides oxygen and nutrients
What happens after maturation of scar tissue?
Fibroblasts and macrophages leave, the vessels die by apoptosis leaving an acellular collagen scar that will contract over time
What does scarring do?
Functionless - just a filler to a gap where tissue has been lost
Distortion of surrounding tissue due to contraction
Where is scarring good and bad?
Positive:
- Heart, small area on the skin
Negative:
- Where a burn is located
- Lungs (Alveoli)
- Kidney (Tubule)
The outcome of acute inflammation depends upon?
Cell/Tissue Type
Type of Injury
What increase the chance of organisation?
Fibrinous Exudate
What is fibrinous exudate?
Fluid with a high fibrin content which denotes greater permeability and the presence of pro-coagulative factors. It frequently occurs in linings and may be removed by fibrolysis and phagocytosis. Otherwise it may lead to the ingrowth of granulation tissue and scarring
What is an Ulcer?
A lesion or ‘sore’ on a body surface like the skin or mucous membranes
Where necrotic tissue has been eroded and can be slough off and removed from the body
What is an abscesses?
An Area of necrosis in a solid organ that is trapped in the body walls of the entire area with granulation tissue
If removed = cystic space
Not removed = Chronically inflammed
Features of Chronic Inflammation?
- Later onset (days)
- Longer duration (weeks- years)
- Involves lymphocytes & macrophages
- Involves further injury & repeated attempts to repair
- Always results in organisation
Outcomes of Chronic Inflammation
Unresolved Acute Inflammation
Repeated Acute Injuries and inflammation
Special Cases where the immune system targets the body
Components of Chronic Inflammation
- Continued injury/necrosis
- Repeated attempts at repair
- Granulation tissue
- —–1 Macrophages
- —–2 Fibroblasts laying down collagen
- —–3 angiogenesis
- Proliferating Parenchymal cells - Lymphocytes
- T cells
- B cells –> Plasma Cells –> Antibodies
What are Lymphocytes?
Part of the acquired immune system
Contains:
- T cells
- B cells –> Plasma Cells –> Antibodies
Feature in chronic inflammation where the immune system is causing problems
- Autoimmune disorders
- Hypersensitivity disorders
Complications of Chronic Inflammation?
Involves continued injury, inflammation and repeated attempts at repair
Healing inevitably by organisation
What are the roles of the Immune System?
Defense against infections
Defence against tumours
Recognition of foreign proteins and tissues
Recognition of other foreign substances
What are four parts of the immune system?
- Non-specific INNATE
- Specific response (slower) ADAPTIVE
- Non-specific reinforcement INNATE
- Memory ADAPTIVE
Describe the Adaptive immune response:
Acquired Immunity
Involves:
- Antigen processing and presentation by macrophages
Leads to either:
- Cell mediated response
- Humoral (antibody) response
- Immunologic memory
Characteristics of Adaptive Immunity:
- Identification/determination of ‘self’ and ‘non-self’
- Specificity (and diversity)
- Memory
What is a Type 1 (immediate) Hypersensitivity?
Overreaction to an antigen
Prototypic disorders:
- Anaphylaxis
- Allergies
- Atopic asthma
Pathologic lesions:
- Vascular dilation leading to oedema
- Smooth muscle contraction
- Mucous production
- Tissue damage
- Inflammation
What is a Type 2 (Antibody-mediated) hypersensitivity?
Antibody that targets proteins for destruction
Prototypic Disorder:
- Autoimmune hemolytic anemia
- Goodpasture syndrome
Pathologic lesions:
- Phagocytosis & cell lysis leading to Inflammation
- Functional impairment without cell injury
What is a Type 3 (Immune Complex-mediated) Hypersensitivity?
Prototypic Disorder:
- Systemic lupus erythematosus
- Some glomerulonephritis
Pathologic lesions:
- Inflammation
- Necrotizing vasculitis (fibrinoid necrosis)
What is a Type 4 (cell-mediated) hypersensitivity?
Sensitised T Lymphocytes are the cause of the cellular and tissue injury
Induce lesions that are part of the immediate hypersensitivity reactions and are not considered a form of type 4 hypersensitivity.
Prototypic Disorder:
- Multiple sclerosis
- Type I diabetes
- Rheumatoid arthritis
- Tuberculosis
Pathologic lesions:
- Cell destruction
- Granuloma formation
Order of blood flow in the circulatory system?
Right Atria - Right Ventricle - Lungs - Left Atria - Left Ventricle - Large Artery - Medium Artery - Small Artery - Capillary - Venule - Vein - Right Atria
What is a Capillary?
1 cell think cell where gas exchange occurs
In what direction do arteries travel?
Away from the heart
In what direction to veins travel?
Towards the heart
Which side of the heart if more powerful?
Left Side
What is the major artery?
The Aorta
Where does the Aorta go?
Comes out of the left ventricle and goes down wards through the thoracic chest and abdomen
Where is the INNER ENDOthelial Lining?
Both artery and vein
Arterial vs Venous
Arterial:
- Smaller Lumen
- Higher pressure
- Thicker Muscle Layer
Venous:
- Largen Lumen
- Smaller Wall thickness and muscle layer
What are the layers of the capillary?
Endothelial Lining and Connective Tissue
Produces anti-coagulative substances that encourage vessels to stay open and prevent clotting
Structure of the Artery
Suppose to be able to push large amounts of blood to the entire body
Requires large contractions from the heart to be able to reach everywhere in the body
Has an elastic layer to hold large volumes of blood in between each heart contraction by expanding the artery
HIGH PRESSURE
Stucture of the Vein
Supposed to be able to dilate and store blood
Requires skeletal muscle contraction to squish the vein closed thus pushing blood back to the heart against gravity
When muscles relax, the valves in the venous system stop backflow.
LOW PRESSURE
What is the volume of blood?
60% systemic veins and venules 15% in systemic arteries and arterioles 12% in Pulmonary blood vessels 8% Heart 5% Capillaries
Vasodilation vs Vasoconstriction
Smooth Muscle can be modified Vasoconstriction: - Contracts - Increase in blood pressure - Too High? Systemic Hypertension
Vasodilation:
- Dilates and relaxes
- Decrease in blood pressure and hypotension
What are Intrinsic Mechanisms?
Autoregulation
Metabolic or myogenic controls
Distribute blood flow to individual organs and tissues as needed
What are extrinsic mechanisms?
Neuronal or hormonal controls
Maintain mean arterial pressure (MAP)
Redistribute blood during exercise and thermoregulation
What does the renal system do
Formation of urine - removal of wastes
Regulates plasma ions (NA, Cl, PO4, K, Ca2
Regulates pH (H, HCO3)
Endocrine function - Vitamin D, RAAS, EPO)
Regulation of blood volume
Regulation of blood pressure
How does RAAS work?
Renin - Angiotensin 2 - Aldosterone System
When the Renal system senses ischemia, Renin is activated and uses ACE to get Angiotensin 2.
Angiotensin 2 can cause potent vasoconstriction and an increase in vascular resistance. It can also increase SNS - Increasing sympathetic tone and heart rate (force of contraction) - increasing vascular resistance.
Angiotensin 2 can trigger ADH increasing thirst and water uptake in DCT thus increasing blood volume
Angiotensin 2 triggers Aldosterone which is a horone released into the adrenal gland to act upon the kidney. It increase Na uptake in DCT, increasing blood volume
RAAS increases blood pressure and hypertension
What is ACE
Angiotensin Converting Enzyme
What is ADH
Anti-diuretic hormone
What is EPO
Erythropoitetin
How does EPO work
A decrease in oxygen in the blood causing hypoxia is identified by the kidney which releases EPO, increasing bone marrow rbc production
What happens if the kidney fails?
No EPO is created causing Anaemia
What is Haemopoisesis
Stem Cells that form cellular components of blood immune cells to inflammation cells
How does Anaemia impact Fetus and Adult differently?
In a fetus, there are more haemopoesis = more red marrow. When there is anaemia, an increase in red marrow is easier due to its excess
In an adult there are less haemopoiesis in red marrow
Define Anaemia:
A decreased number or quality of red blood cells
- Excessive loss or RBC’s
- Reduced Synthesis (decreases EPO, dietry deficiency of iron, vitamin B12 or folic acid
- Increased Destruction
Symptoms of Anaemia:
Weak Lethargic Dizzy Insomnia Sad Depressed Confused Breath shortness Pale Gums Eyelid Linings Tachycardia and Arrhythmia
What are the primary lymphoid organs?
Bone Marrow
Thymus
What are secondary lymphoid organs?
Spleen
Lymph Node
Lymphoid tissues of the Alimentary Tract and Respiratory Tract
What happens in lymph nodes?
Physical filtration of lymph fluid causing a removal of any particulate matter and bacteria
The cortex contains primary lymphoid follicles
What are lymphoid follicles?
Are sites of B lymphocytes storage and proliferation
Includes naive lymphocytes and memory cells
Contain Germinal centers
What are Germinal Centres?
Contain proliferating lymphocytes
- Antigenic stimulation –> Plasmablasts –> Proplasmocytes
Proplasmocytes move to periphery of node and mature into plasma cells (Secrete antibody)
What happens in the spleen?
Filters circulating blood
Immunological response against blood borne antigens
Removal of damaged and old red cells
- B lymphocytes around arteriole
- T lymphocytes in marginal zone
- Antigen Presenting cells for immune attack
What are the functions of the liver?
Digestion: Production of bile salts (from cholesterol) used in the digestion of fats
Metabolism: Carbohydrates, fats, proteins, vitamins, bilirubin, toxins
Storage of Vitamins
Metabolism of Bilirubin
Excretion of substances: Bilirubin, drugs, etc.
Role of Metabolism?
Synthesis of Cholesterol, Urea
Synthesis of lipoproteins, proteins
Glucongeogenesis, glycogenesis
Detoxification
What is the portal Triade.
Located on the corners of the liver lobule
Drains bile duct through
Blood supplying and transportation for metabolism
Venous and Artery enter at the same site
How does blood drainage in liver work?
Blood supply arrives together from all other organs and systems through the portal tract, mix down leaky sinusoids and drain into the central vein
The central veins comes together and forms the hepatic veins and into the inferior vena cava
Pathways to Systemic Odema:
Heart Failure - Increase Capillary hydrostatic pressure - Oedema
Heart Failure - Decrease Renal blood flow - Activation of RAAS - Retention of NA and H2O - increase in blood volume - Oedema
Renal Failure - Retention of NA and H2O - increase in blood volume - Oedema
Malnutrition, Decrease in hepatic Synthesis, Nephrotic syndrome - Decrease in plasma albumin - decrease in plasma osmotic pressure - oedema
Consequences of Haemorrhages?
Determined by: Site, Amount Lost, Speed of Loss
Healthy adults can quickly lose >20% at a slower rate, without serious consequences
Hypovolemic shock
Iron Deficiency Anaemia
What happens in a Haemorrhage?
Accumulation of blood causing a haematoma
What is a haematoma?
“bruise”
Small Haematomas = Petechiae, pupura
Large Subcutaneous haematomas = Ecchymoses
What are the signs of shock?
Low peripheral blood flow
Escessive symphathetic stimulation
Thirst, altered skin temperature, decreased Blood pressure, increased heart rate, decreased venous pressure, decreased urine output
Decreased cellular perfusion, increased lactic acid, Death
Define Thrombus:
Blood clot that is attached to the wall of a vessel or the heart
Define Embolus:
Undissolved mass travelling in the blood
Define Aneurysm:
An ABNORMAL, LOCALISED, DILATION of an artery or ventricle
What causes an infarction?
Haemorrhage or Ischaemia
1- Blcokage in arterial system - Ischaemia - necrosis
2- Blockage in venous system - congestion of poorly oxygentated blood - Haemorrhage - Necrosis
What is the Normal haemostatic Process:
The maintenance of fluid blood and the formation of a haemostatic clot in response to injury
Naturally produces anti-coagulents
What are the three components of normal haemostatic process?
- Vascular wall, endothelium
- Platelets
- Coagulation Cascade
