Session 7 Flashcards
The size of a cell population depends on the rate of… (3)
Cell proliferation
Cell differentiation
Cell death by apoptosis
______________ genes regulate normal cell proliferation
Proto-oncogenes
Cell proliferation is controlled by…
Chemical signals which either stimulate or inhibit cell proliferation
Chemical signals which stimulate/inhibit cell proliferation bind to a receptor resulting in…
Modulation of gene expression
Decide 4 different possible outcomes for cells as a result of chemical signals
Survive - resist apoptosis
Divide - enter cell cycle
Differentiate - take on specialised form/function
Die - undergo apoptosis
With regards to the cell cycle, state two things that can result in increased growth
Shortening of the cell cycle
Conversion of quiescent cells to proliferating cells (entering them into cell cycle)
Name three checkpoints of the cell cycle
G1 checkpoint G2 checkpoint R point (Restriction point)
What does the G1 checkpoint of the cell cycle check?
Is cell big enough?
Is environment favourable?
Is DNA damaged?
What does the G2 checkpoint of the cell cycle check?
Is cell big enough?
Is all DNA replicated?
In the normal state what happens to cells with damaged DNA that try to replicate?
Cannot replicate - attempts to repair damage or cell pushed towards apoptosis
What is the most critical checkpoint of the cell cycle?
R point (Restriction point)
What happens as a result of activation of the R point?
Delay of the cell cycle and triggering of DNA repair mechanisms/apoptosis via p53
The majority of cells that pass the R point of the cell cycle will…
Complete the cell cycle
What is the most commonly altered cell cycle checkpoint in cancer cells?
Restriction (R) point
In which phase of the cell cycle is the R point found?
Towards the end of G1
Which proteins and enzymes control the cell cycle?
Cyclins
Cyclin dependent kinases
How do cyclic dependent kinases (CDKs become active)?
Binding with cyclins
How does the activation of CDKs affect the cell cycle?
The activated CDKs phosphorylate other molecules allowing the cell cycle to progress. Different cyclins produced at different parts of the cell cycle.
Different cyclins are produced at different parts of the…
Cell cycle
Do cells have a limit to how much they can divide?
Cells that do not contain telomerase have a limit to how much they can divide
Which cells contain telomerase to maintain telomere length and increase the number of divisions they can undergo?
Stem cells
Cancer cells
What is meant by the Hayflick number?
The number of times a cell without telomerase can typically divide
What is the average Hayflick number in humans?
61.3
What is hyperplasia?
Increase in number of cells
What is hypertrophy?
Increase in cell size
What is atrophy?
Decrease in cell size
What is metaplasia?
Where cells are replaced by cells of a different type
Are the vast majority of cellular adaptations, reversible or irreversible?
Reversible
Hyperplasia can occur in which sorts of tissues?
Labile
Stable
What causes hyperplasia in tissues? (2)
Increased functional demand
Hormonal stimulation
Hyperplasia remains under _______________ control
…and is reversible/irreversible?
Physiological
Reversible
Repeated cell divisions seen in hyperplasia exposes the cell to increased risk of…
Mutations/Neoplasia
In what type of tissues is hypertrophy seen?
Labile
Stable
Permanent (especially)
What can cause hypertrophy of cells? (2)
Increased functional demand
Hormonal stimulation
Hypertrophied cells contain more…
Structural components
In labile and stable tissue, hypertrophy usually occurs along with…
Hyperplasia
Give an example of physiological hypertrophy and pathological hypertrophy
Phys - pregnant uterus
Path - RV hypertrophy
Do athletes get cardiac muscle hypertrophy? How does this compare to someone with hypertension?
Yes, to some extent
Not as much, in hypertension the heart doesn’t get a chance to rest
What is compensatory hypertrophy? In what organ is it commonly seen?
Increase in size of an organ/tissue when called on to do additional work of a destroyed/impaired organ
Kidneys
What is atrophy?
Decrease in number/size of cells resulting in a decreased tissue size
In atrophied cells there is a reduction in…
Cell components
Give an example of physiological atrophy
Ovarian atrophy in post menopausal women
What causes atrophy of disuse?
Reduced functional demand/workload
What causes denervation atrophy? What can this result in?
Loss of innervation
Wasting of muscles
Which disease is a prime example of atrophy of extracellular matrix?
Osteoporosis
What is metaplasia? What causes it?
Reversible change of one differentiated cell type to another
Altered stem cell differentiation
When can metaplasia take place?
When cells that are sensitive to stress are substituted by cells better able to withstand the stress
Metaplasia can be a prelude to…
Dysplasia and cancer
Where does no metaplasia take place?
Across germ layers
In which sorts of cell types can metaplasia take place?
Labile
Stable
Describe an example of metaplasia and its cause
Bronchial pseudostratified ciliated epithelium —> stratified squamous epithelium
Cigarette smoke
Describe the metaplasia that can take place in the bronchi/bronchioles due to cigarette smoke
Pseudostratified ciliated epithelium —-> stratified squamous epithelium
What is aplasia? What type of disorder is this?
Complete failure of a specific organ or tissue to develop
Embryonic disorder
As wells as describing the complete failure of an organ/tissue to develop, aplasia can be used to describe an organ whose cells…
Give an example
Have ceased to proliferate
E.g. Bone marrow in aplastic anaemia
What is hypoplasia?
Underdevelopment or incomplete development of a tissue/organ at embryonic stage
What is involution? Give an example.
Normal programmed shrinkage of an organ
Uterus after childbirth
What is reconstitution? It is very rare in humans, give an example.
Replacement of a lost part of the body
If a small child (under 4) cleanly cuts the tip off their finger off it may grow back
What is atresia? Give an example of where this can take place
Congenital imperforation (closing) of an opening
Anus, vagina and small bowel
What is dysplasia? It is often…
Abnormal maturation of cells within a tissue
Pre-cancerous
What is the difference between dysplasia and neoplasia?
Dysplasia - abnormal maturation of cells in a tissue
Neoplasia - abnormal growth of a tissue
Dysplasia - potentially reversible
Neoplasia - irreversible
Give 4 general effects of trauma
Bleeding
Infection (possible sepsis)
Specific organ/system effects
Multi-organ failure/dysfunction
Name 4 types of intercranial haemorrhage
Extradural
Subdural
Sub-arachnoid
Intracerebral
Give two examples of closed brain injuries
Contusions
Diffuse axonal injury
Name 4 potential consequenes of head injury
Raised intracranial pressure Reduced Glasgow (consciousness) score Specific neurological defects Infection
How are rib fractures most commonly treated?
With analgesia
Rib fractures can result in… (3)
Pulmonary contusions
Pneumothorax
Haemothorax
What is a contusion?
An area of injured tissue where blood capillaries have leaked into - BRUISE
What is a pneumothorax?
What is a haemothorax?
Air in the pleural cavity
Blood in the pleural cavity
What is the most fatal type of aortic injury?
Aortic transection
Name 4 types of abdominal injury
Liver laceration
Spleen laceration
Intestinal perforation
Pancreatic injury
Fractures of the spine can potentially lead to ______________ problems
Neurological
What type of force is required for a pelvic fracture to occur? What is special about this break? What can it lead to?
Lots of force
Breaks in two places
Heavy bleeding
Name 4 potential causes of vascular injury due to trauma
Stab wounds
Gun shot wounds
Impalement
Plate glass accidents
State 6 systemic effects of burns
Release of cytokines/inflammatory mediators Cardiovascular changes Myocardial contractility decreased Respiratory changes Metabolic changes Immunological changes
Describe the cardiovascular changes seen in burns
Increased vascular permeability —> loss of fluid/protein
What effect can decreased myocardial contractility as a result of burns have?
Can cause hypotension/hypoperfusion and ischaemia
Describe the respiratory changes seen in burns (2)
Direct inhalation of toxic fumes
Adult respiratory distress syndrome
Describe the metabolic changes seen in burns
Increased metabolic rate - aggressive enteral feeding required to decrease catabolism
Describe the immunological changes seen in burns
Down regulation of the immune response
Haemorrhage can result in _______________ shock
Hypovolaemic
When can haemorrhage (blood loss) become life-threatening?
When blood loss is over 20%
How does haemorrhage affect…
I) cardiac output
II) perfusion of organs
Impaired (reduced)
Reduced
What does SIRS stand for? What is SIRS?
Systemic Inflammatory Response Syndrome
Where there is a systemic inflammatory response to inflammatory mediators but no specific site of infection to account for it
For someone to have SIRS (or sepsis) they must have at least 2 of the following criteria…
I) temperature II) heart rate III) respiratory rate IV) pCO2 V)WBCs
> 38.5, <36
> 90 bpm
> 20 breaths/min
<32 mmHg (low)
> 12000, <4000
Sepsis = SIRS +
Suspected/Confirmed Infection
Severe sepsis = sepsis + at least one sign of…
Organ dysfunction
Sever sepsis can lead to…
Septic shock
What can the mottled skin seen in sepsis be attributed to?
Poor perfusion to the skin
Sepsis can result in inappropriate activation of the coagulation system and which condition…
Disseminated Intravascular Coagulopathy
Describe the typical capillary refill time in sepsis. Is this higher or lower than normal?
> 3 seconds
Higher
How can sepsis affect the kidneys? Why?
Can cause acute kidney injury
Reduced perfusion to the kidneys
In sepsis you may see acidosis, lactate levels above…
2 mmol/L
In sepsis what sort of platelet count will you see?
Low platelets - < 100
Septic shock = sever sepsis + one of the following conditions…
I) mABP
II) Lactate
< 60 mmHg after adequate fluid resuscitation
High lactate - > 4 mmol/L
What drugs are required to maintain blood pressure in septic shock?
Inotropes - e.g. Noradrenaline
What does MODS stand for? What is MODS/multi-organ failure usually caused by?
Multi-organ dysfunction syndrome
Hypometabolism
Immunosuppression
Name some consequences/presentation of multi-organ failure/MODS
Acute kidney injury ARDS Cardiac dysfunction Encephalopathy GI disturbance Liver dysfunction Coagulopathy Bone marrow suppression
State two consequences of acute kidney injury due to MODS/failure
Acidosis
Uraemia
What does ARDS stand for? What does it result in?
Acute respiratory distress syndrome
Impaired gaseous exchange
Cardiac dysfunction due to MODS/failure can result in… (2)
Reduced cardiac output
Hypotension
What does encephalopathy due to MODS/failure result in?
Reduced conscious level
Describe the GI disturbances that may occur in MODS/failure
Ischaemia
Perforation
Ileus
Pancreatitis
What happens in ileus due to MODS/failure?
Bowel stops working and fills with fluid
What can result from liver dysfunction due to MODS/failure?
Jaundice
Low albumin
Give an example of a condition related to coagulation that can result from MODS/failure
DIC - disseminated intravascular coagulopathy
Bone marrow suppression as a result of MODS/failure can result in… (2)
Anaemia
Neutropenia
Is recovery from MODS/Multi-organ failure possible?
Possible with intensive organ support and treatment of any underlying cause - contributes to many deaths