Flashcards in Pathological Processes - Semester 2 Deck (347):
What is the difference between HISTOLOGY and CYTOLOGY?
HISTOLOGY - involves viewing tissue sections under microscope; cellular architecture and atypia are assessed; higher accuracy than cytology; more invasive
CYTOLOGY - non-invasive; fast, cheap and safe; used in preliminary testing; study of cells sucked out / scraped from an organ or extracted from a body fluid
What is the most commonly used fixative?
Formalin (formaldehyde in water)
What does a 'fixative' do?
Holds tissue in suspended animation
Inactivates tissue enzymes
Prevents bacterial growth
What is used to embed the fixed tissue for histological examination?
What is a 'microtome' used for in the preparation of a slide for microscopy?
Microtome cuts thin slices (3-4 microns thick) so that you can see through the sections using a microscope
What does H&E stand for?
What does haematoxylin stain, and what colour?
Haematoxylin stains nuclei purple
What does eosin stain, and what colour?
Eosin stains cytoplasm, proteins, collagen and CT pink
In what situation might a frozen section be necessary instead of histology?
Time constraints - is this tissue cancerous or not?
The result will determine the course of the surgery.
How is a frozen section produced?
(bypass formalin fixation and paraffin wax embedding)
Rapidly freeze small fresh piece of tissue using the CRYOSTAT
Thinly slice the piece of tissue
Mount and view using microscope
Give 4 causes of cell injury and death
Hypoxia (anaemia, ischaemia, histocytic, hypoxaemia)
Physical agents (trauma, radiation, electric currents)
Chemical agents and drugs (poisons, O2 extremes, alcohol)
How does hypoxic injury occur?
Cell deprived of O2
Mitochondrial ATP production stops
Slowed down activity of ATP driven membrane ionic pumps
Na+ and H2O enter the cell
Cell swells, plasma membrane stretches
Glycolysis allows cell to stay alive temporarily (so increased lactic acid and decreased pH)
Heat shock response
Ca2+ enters cell, activating harmful enzymes (phospholipases, ATPase, endonucleases, proteases)
ER and other organelles swell
Enzymes leak out of lysosomes and attack cytoplasmic components
Cell dies (burst of bleb)
Why is it sometimes worse if blood returns to the tissue that has been ischaemic but isn't yet necrotic THAN if blood flow hadn't been restored?
What is the mechanism of ischaemic-reperfusion injury?
Increased production of O2- free radicals with reoxygenation
More neutrophils, more inflammation and tissue injury
Delivery of complement proteins and activation of the inflammation pathway
Define "free radical"
Highly reactive, uncharged atom/molecule with a single unpaired electron in an outer orbit. Goes on to produce more free radicals. A reactive oxygen species with a single unpaired electron on the outer orbit.
How do free radicals injure cells?
Free radicals attack lipids in cell membranes, damage proteins, carbohydrates and nucleic acids. They are mutagenic.
How does the body defend itself against free radicals?
Vitamins A, C and E
Free radical scavengers
What protein do cells release when they are injured (in order to protect themselves) and what does this protein do?
Heat shock proteins (e.g. ubiquitin)
Maintains protein viability and maximises cell survival
Characteristics of reversible cell injury under an electron microscope (3)
cell organelles swell
ribosomes separate from the ER
Characteristics of irreversible cell injury under an electron microscope (3)
Increased cell swelling
lysis of ER
densities in swollen mitochondria
What is the difference between oncosis and necrosis?
Oncosis is the changes to the injured cell prior to death
Necrosis is the changes to the dead cell after it has been dead for some time
What is the difference between necrosis and apoptosis?
Necrosis - cell died with swelling; due to cell injury
Apoptosis - programmed cell suicide; cell died with shrinkage; regulated intracellular process where the cell itself degrades its own nuclear DNA and proteins
How is necrotic tissue removed from an area?
Phagocytosis by white cells
If some tissue remains, it calcifies - DYSTROPHIC CALCIFICATION
What are the four types of necrosis?
Name a disease that characteristically results in caseous necrosis
What is the difference between coagulative necrosis and liquifactive necrosis?
Coagulative necrosis - solid organs - proteins denature and coagulate
Liquifactive necrosis - loose tissues - proteins undergo autolysis
What is the difference between gangrene and necrosis?
Gangrene is necrosis visible to the naked eye
What is the relationship between infarction and ischaemia?
Ischaemia (restriction of blood supply) ----> infarction (death of tissue)
What are the two types of infarction?
White (anaemic) - after occlusion of an end artery
Name a molecule that leaks out from an injured cell
Under a light microscope, how does a cell undergoing apoptosis appear?
Fragmentation of nucleus - karyorrhexis
Under an electron microscope, how does a cell undergoing apoptosis appear?
Cytoplasmic BUDDING (NOT BLEBBING)
________ control and mediate apoptosis
Which abnormal protein accumulates in alcoholic liver disease?
Give an example of a reason for exogenous pigment accumulation
Coal dust, tattoo
Give an example of a reason for endogenous pigment accumulation
What are the two causes of pathological calcification?
What is the difference between dystrophic and metastatic calcification?
Dystrophic - localised in one area of dying tissue, no abnormality in Ca2+ metabolism
Metastatic - body-wide/generalised, abnormality in Ca2+ metabolism
Give 3 consequences of cellular aging.
Accumulation of damage to DNA
Accumulation of damage to cellular components
Accumulation of abnormally folded proteins
Accumulation of lipofuscin pigment
Reduced ability to replicate
Give 2 effects on liver of chronic excessive alcohol intake
acute alcoholic hepatitis
Acute inflammation is a rapid response to an injurious agent that aims to do what?
Deliver mediators of host defence (leucocytes and plasma proteins) to the site of injury and so limit tissue damage, protect against infection, clear damaged tissue
Acute inflammation is carried out by:
a) innate immune system, or
b) adaptive immune system?
a) innate immune system
What is the difference between exudate and transudate?
Exudate - protein rich - develops in inflammation
Transudate - protein poor - e.g. seen in heart failure
Give 3 major causes of acute inflammation
Acute phase hypersensitivity reactions
5 cardinal signs of infection:
Loss of function
Name the 3 tissue changes in acute inflammation:
Formation of a fluid exudate
Explain the change in blood flow that occurs in acute inflammation
Acceleration of flow in arterioles and capillaries
Increased capillary pressure
Why is an increased capillary flow important in acute inflammation?
Increased delivery of fluid and leucocytes to injured area
What is the main force pushing fluid out of blood vessels?
capillary hydrostatic pressure
What is the main force pushing fluid into blood vessels?
colloid osmotic pressure
In four steps, explain how vascular leakage occurs in acute inflammation.
1) Endothelial contraction ----> gaps
2) Plasma proteins leak into interstitial space
3) Upstream vessel dilates
4) Net flow of fluid out of vessels - OEDEMA
Why is a fluid exudate useful in acute inflammation?
Delivers plasma proteins to site of injury
Excess fluid drains in the lymphatics taking antigens + microorganisms with it, presenting them to lymph nodes
Neutrophils are "end cells". What are end cells?
Give the four steps how neutrophils get out of the vessels to kill microorganisms:
1) Margination - neutrophils line up on the edge of the vessel due to stasis
2) Rolling - Neutrophils roll along the endothelial surface
3) Adhesion - stick to the endothelium
Then recognition, attachment and phagocytosis
Give four important chemical mediators in acute inflammation
Cytokines and chemokines
What is the effect of prostaglandin?
Makes skin more sensitive to pain and causes fever
Which medication stops the production of prostaglandin?
NSAIDs and aspirin
What is the effect of histamine on the body?
increased vascular permeability
Which cells store histamine in the body?
Mast cells, basophils and platelets
How does the complement system kill bacteria?
Punches holes in bacteria
Causes inflammation also
C3b is an opsonin, aiding the phagocytosis of antigens
What is the function of a cytokine, such as TNF?
Messengers between cells
Give three local complications of acute inflammation
Damage to normal tissue
Obstruction of tubes, compression of vital structures
Loss of fluid
Pain and loss of function
Give three systemic complications of acute inflammation
Leucocytosis (increaased leucocytes circulating)
Acute phase response
Give 3 types of exudate
Give the type of inflammation (acute or chronic), a complication and causative organism of LOBAR PNEUMONIA
acute exudative inflammation secondary to airborne infection of the entire pulmonary lobe
by Streptococcus pneumoniae/pneumococcus
complication: lung abscess, pleural effusion, lung fibrosis
Name a causative organism of ascending cholangitis
Name one inherited disorder of the acute inflammatory process
Hereditary angio-oedema - inherited deficiency of C1-esterase inhibitor, attacks of non-itchy cutaneous angio-oedema
Alpha-1 antitrypsin deficiency - so proteases released from neutrophils act unchecked and damage normal lung and liver tissue as they are not deactivated
Chronic granulomatous disease - phagocytes cannot generate the oxygen burst
What is chronic inflammation?
CHRONIC response to injury with associated fibrosis
What is the difference between chronic and acute inflammation?
Chronic takes over acute after a few hours if the injurious agent is not removed
What are the dominant cells in chronic inflammation?
Give a disease where chronic inflammation occurs without any preceding acute inflammation.
Give the THREE main roles of macrophages in chronic inflammation
Produces important proteins and enzymes
Controls other cells via cytokine release
Presentation of antigens to immune system
What is the major difference in role between T and B lymphocytes?
T - cytotoxic functions
B - makes antibodies
What are macrophages called when they are circulating in the blood?
Do macrophages replicate?
Yes, unlike neutrophils!
Are lymphocytes usually present in tissues?
No! So their presence indicates antigenic material has been there.
Which cell type dominates in allergic reactions / parasitic infections?
Which type of giant cell is characteristic of tuberculosis?
Langhan's giant cell
What are the three kinds of giant cells involved in chronic inflammation?
Touton - lesions with high fat content
Langhan's - TB
Give three possible complications of chronic inflammation
XS fibrosis - e.g. cirrhosis
Impaired function - e.g. Crohn's
Tissue destruction - e.g. healthy tissue taken over by fibrosis
Define the term "granuloma"
organised collection of macrophages
In which case would granulomatous inflammation occur?
Granuloma forms around a particle that is DIFFICULT TO DISSOLVE in an effort to destroy it.
What are the two types of granulomas?
Foreign body and Hypersensitivity granulomas
What is the difference between foreign body and hypersensitivity granulomas?
Foreign body - forms around material that is NOT antigenic
Hypersensitivity - forms around material that IS antigenic
Which kind of cells make up a foreign body granuloma
Lymphocytes surrounding epitheloid cells
(In TB, you also have caseous necrosis at the centre of the granuloma plus Langhan's giant cells involved too)
What is the role of thrombin in clot formation?
Thrombin: fibrinogen ---> fibrin (insoluable)
What is the name of the process by which clots are DESTROYED?
What are the three steps of haemostasis?
1) Severed artery contracts
2) Primary haemostatic plug of activated platelets
3) Secondary haemostatic plug of fibrin filaments (about 30 mins after initial injury)
Which cell produces PLATELETS?
Name two platelet activators.
ADP (released from activated platelets and injured RBCs)
Once activated, what do platelets stick to?
Activated platelets stick to von Willebrand factor on the exposed subendothelium
In one simple statement, how does aspirin prevent clotting?
Inactivates an enzyme involved in platelet aggregation (thromboxane A2)
How does thrombin become activated?
Some clotting factors require Vitamin __ for their synthesis
What is the difference between intrinsic and extrinsic pathways to blood clotting?
Intrinsic - all factors contained in blood and no vessel needs to be broken to kickstart the process
Extrinsic - needs a "tissue factor" which is not present in blood
Name an endothelial secretion that opposes blood clotting
tissue plasminogen activator
Name an endothelial secretion that favours blood clotting
Von Willibrand factor
____ __________ helps to pull the sides of small wounds together and may toughen the clot by squeezing water out
Name 2 plasminogen activators
Tissue plasminogen activator
What is the role of plasmin?
Dissolves fibrin (fibrinolysis) and therefore thrombi and thromboemboli
How does the clotting cascade set fibrinolysis in motion?
Becauses fibrin increases the activity of tissue plasminogen activator which produces plasmin which causes fibrin ----> FDPs
Name one inherited bleeding disorder
Haemophilia A + B
Von Willebrand Disease
How do patients with haemophilia present?
Recurrent bleeding into joints
What kind of disease is haemophilia in terms of how it is associated with chromosomes?
X linked recessive
How can you diagnose haemophilia using blood coagulation tests? e.g. platelet count, bleeding time, PT, APTT
normal platelet count
normal bleeding time
normal PT (so extrinsic pathway is fine)
BUT abnormal APTT (so intrinsic pathway is affected)
What really is the problem in people with haemophilia?
Cannot produce enough fibrin so impaired clotting despite normal platelets
What is the problem in people with von Willebrand disease?
Deficient / abnormal vWF
How can you diagnose von Willebrand disease using blood coagulation tests? e.g. platelet count, bleeding time, PT, APTT
Raised bleeding time
(because platelets "stick less" to the endothelium so less platelet aggregation and hence, clotting)
What is the inheritance pattern of von Willebrand disease?
What is thrombocytopenia?
Low platelet count
How does thrombocytopenia show up in blood coagulation tests?
prolonged bleeding time
normal PT + APTT (as extrinsic and intrinsic pathways are intact, the problem is the platelets!)
Give three causes of thrombocytopenia
Sequestration e.g. hypersplenism
Dilutional e.g. after blood transfusion
Decreased platelet survival e.g. immunological destruction, non-immunological destruction (DIC)
Decreased platelet production e.g. bone marrow infiltration by malignancy, drugs (cytotoxic)
Give 1 cause of thrombophilia
Protein C/S deficiency
What is disseminated intravascular coagulation?
clotting activator gets into blood and microthrombi are formed throughout the circulation, using up fibrin, platelets and coagulation factors and causing haemorrhage
Give three causes of DIC
What is the treatment for DIC?
TREAT THE CAUSE
Give 2 ACQUIRED coagulation factor disorders
Anticoagulants e.g. warfarin
Vitamin K deficiency
Regeneration (of cells) only occurs in ____ / _____ tissues (NB, not a type eg muscle, rather the general name for a group of these tissues!)
What is also known as "healing by primary intention"?
What is also known as "healing by secondary intention"?
Why does healing by fibrous repair occur in some cases instead of just regeneration?
Significant tissue loss/ if collagen or CT framework is destroyed
Ongoing chronic inflammation
Give an example of a labile tissue
Surface epithelia of bone marrow
Columnar epithelia of GI tract and uterus
Give an example of a permanent tissue
Cardiac muscle cells
Skeletal muscle cells
Give an example of a stable tissue
Parenchymal cells of liver, kidneys, pancreas
What is the difference between labile, stable and permanent tissues?
Labile - continuously dividing tissues as cells are short lived
Stable - rapid division in response to stimuli, quiescent
Permanent - non-dividing tissues
Stem cells undergo assymetric replication. What does this mean?
When the stem cell divides, it produces a stem cell like itself and a differentiated cell
Give 2 places where stem cells can be found in the body
Liver, between hepatocytes and bile ducts
Epidermis, in basal layer
Intestinal mucosa, at bottom of crypts
What is the difference between totipotent, multipotent and unipotent stem cells?
Unipotent - produces one type of differentiated cell
Totipotent - produces ANY type of differentiated cell (this is an embryonic stem cell)
Multipotent - produces several types of differentiated cell
Give an example of a multipotent stem cell
Haemopoietic stem cell of the bone marrow
Which three cell types are involved in fibrous repair?
Inflammatory cells like neutrophils, macrophages which phagocytose the debris
Endothelial cells (angiogenesis)
Fibroblasts and myofibroblasts
What are the four steps of the fibrous repair process?
Phagocytosis... of necrotic tissue debris
Proliferation... of epithelial cells - angiogenesis
Proliferation... of fibroblasts and myofibroblasts which synthesise collagen and cause wound contraction
Fibrous scar.... forms then matures and shrinks (myofibroblasts)
Enzymatic modification of the polypeptide alpha chain in collagen synthesis involves hydroxylation which requires Vitamin ___.
In collagen synthesis, procollagen is cleaved to produce _______ which goes on to polymerize, forming fibrils.
At the last step of collagen synthesis, cross linkage of collagen fibres increases ____ ______
Name an acquired condition that results in defective collagen synthesis?
In which cellular component does the intracellular part of collagen synthesis occur?
Name three inherited conditions which result in defective collagen synthesis.
What are 3 characteristic features of Ehlers-Danlos syndrome?
Hyperextensible skin, fragile skin, hypermobile joints, poor wound healing
What are 2 characteristic features of Alport syndrome?
Dysfunction of glomerular basement membrane, cochlea of ear and lens of eye
Haematuria in children
What are three elements that granulation tissue consists of?
myofibroblasts and fibroblasts
chronic inflammatory cells
What is a growth factor?
Polypeptides that act on cell surface receptors
Stimulate transcription of genes that regulate entry of cell into the cell cycle
Name the three ways to describe cell to cell signalling:
1) endocrine... to a distant cell, via blood stream
paracrine - to a nearby cell
autocrine - to itself
Name two types of cells that produce growth factors
What is the similarity between cadhesins and integrins?
Both are adhesion molecules
What is the difference between cadhesins and integrins?
Cadhesins bind cells to each other and integrins bind cells to extracellular matrix
What are the five steps in healing of bone fractures?
2) Granulation tissue
3) Soft callus
4) Hard callus
5) Lamellar bone
Name five local factors that affect growth and repair
Name four systemic factors that affect growth and repair
Obesity (more tension on wound)
Genetic disorders e.g. Ehlers-Danlos
Drugs e.g. steroids inhibit collagen synthesis
Why does taking steroids make healing time longer?
Steroids inhibit collagen synthesis
Why do diabetic patients have prolonged healing time?
decreased resistance to infection
microangiopathy means decreased blood to site
Give three complications of fibrous repair
Formation of fibrous adhesions
Dusruption of normal organ architecture
Loss of function (replacement of specialised tissue with scar tissue)
OVERPRODUCTION of scar tissue e.g. keloid scar
Excessive scar contraction e.g. fixed flexures
What is a keloid scar?
Overgrowth of fibrous tissue that exceeds borders of the scar and does not regress - common in Afro-Caribbean population
Why does cartilage not heal well?
No blood supply
No lymphatic drainage
When a peripheral nerve is severed, it can regenerate, elongating slowly guided by _______ cells
What is an atheroma?
Accumulation of Fatty deposits found on the inside of artery walls
The gruel-like necrotic material present in atherosclerotic plaques
What is atherosclerosis?
Thickening and hardening of arterial walls due to buildup of fatty plaques and hypertension/diabetes (which damages the walls)
What is the difference between atherosclerosis and arteriosclerosis?
Atherosclerosis - artery walls only
Arteriosclerosis - artery and arteriole walls affected
What are the five steps leading to formation of atherosclerotic lesions?
1) chronic endothelial injury
2) monocyte accumulation, growth factors released, cytokines released, platelet adhesion
3) smooth muscle emigration from media to lamina
4) macrophages and smooth muscle cells engulf lipid to form foam cells
5) proliferation of smooth muscle cells, collagen and matrix deposition, extracellular lipid deposition, neovascularisation
What is a foam cell?
Macrophage/smooth muscle cells engulf lipid to form foam cells
How does a fatty streak evolve in atherosclerosis?
Fatty streak ---> Simple plaque ---> Complicated plaque
How does a fatty streak appear on a macroscopic level?
Yellow and slightly raised, lipid deposits in intima
What is the difference between the macroscopic appearance of simple and complicated plaques on arterial walls?
Simple - (irregular outline), widely distributed and raised; yellow or white
Complicated - haemorrhage into plaque and calcification
State two early microscopic changes in atherosclerosis
Accumulation of foam cells
proliferation of smooth muscle cells
extracellular lipid deposition
Name three later microscopic changes in atherosclerosis
Ingrowth of blood vessels
disruption of internal elastic lamina
What are three of the most common sites for atherosclerosis
What are three ways to prevent atherosclerosis?
reduce fat intake
reduce alcohol intake
What are three ways to intervene in a patient with atherosclerosis?
Lipid lowering drugs
Give three effects of severe atherosclerosis?
Abdominal aortic aneurism
ischaemic heart disease - MI, angina pectoris, arrhythmia
cerebral ischaemia - cerebral infarction (stroke), transient iscaemic attacks
peripheral vascular disease - gangrene, ischaemic rest pain
Give 6 risk factors of atherosclerosis
smoking - increases platelet aggregation
hypertension - damages endothelium due to raised pressure
infection - H. pylori, Cytomegalovirus
Why do smokers have an increased risk of atherosclerosis?
Increased platelet aggregation
Which 6 types of cells are involved in atherosclerosis?
smooth muscle cells
What is a "thrombus"?
solid mass formed from the constituents of blood within the heart or vessels during life
Thrombosis occurs when three changes occur... these three changes collectively are known as ___________________
What are the three changes that occur which result in thrombosis?
Changes in vascular wall (endothelial damage)
Changes in blood flow (slow or turbulent flow)
Changes in the blood (hypercoagulability)
Why is there an increased risk of thrombi in the lower limbs in pregnancy?
Because two of the three factors of Virchow's triad occur - hypercoagulability and stasis (due to pressure on the large veins in the pelvis by the uterus)
Give three cases in which there is endothelial damage, which may result in thrombosis.
following an MI
secondary to hypertension
scarred heart valves
after trauma or surgery
on the surface of atherosclerotic plaques when they break open
In clotting when there is endothelial damage, to what do platelets adhere?
Exposed Von Willibrand factor
Imagine there is endothelial damage but blood flow is fast as usual. Why will this not result in a thrombus?
Because current washes away platelets, clotting factors and chemical mediators and the thrombi can't grow.
Why is blood hypercoagulable in pregnancy, after surgery, fractures or burns?
Increased levels of fibrinogen and factor VIII
Why are platelets concentrated along the endothelium?
Because they are the smallest formed elements in the blood
Describe the process of the formation of a thrombus
Firbinogen binds platelets together
Fibrin grows out of the platelet layer
Fibrin traps RBCs (so white layer of platelets is covered by a red layer of RBCs and fibrin)
Surface of red layer is thrombogenic so platelets stick to exposed fibrin
What are "lines of Zahn"?
Laminations in the thrombus that are visible to the naked eye (because in a thrombus there are layers of white platelets and red blood cells/fibrin)
What is "thrombophlebitis"?
Painful superficial thrombi (in superficial veins) which have associated inflammation in the wall of the vein
What is the difference between parietal and occlusive thrombi?
Parietal - attached to the wall of vessel and restrict the vessel partially
Occlusive - completely obstruct the lumen
What is the specific name for a thrombus found on a cardiac valve?
What are four possible outcomes of a thrombus?
Resolution - dissoved
Propagation - grows
Organisation - fibrous repair and forms a fibrous scar
Recanalisation - new channels lined with endothelium run through the occlusion and restore blood flow
Embolisation - part of the thrombus breaks off and embolises
What are two most common clinical effects of thrombosis?
1) occlusion of an artery ---> ischaemia and infarction
2) embolisation resulting in artery occlusion distant to the site of the thrombus
3) congestion and oedema in the venous bed and associated pain
4) repeated miscarriages
What is an embolism?
Sudden blocking of an artery by a foreign material brought to its current position via the blood current (embolus)
What is an embolus?
Solid, liquid or gas that is carried by the blood and is large enough to become impacted in a vascular lumen
What is a thromboemboli and what is the difference between it and just an emboli?
Thromboemboli are derived from thrombi, whereas an embolus could be any solid, liquid or gas that has become impacted in a lumen, which includes thromboemboli but many others as well e.g. fat emboli....
What are 5 things an emboli can be composed of, besides platelets and fibrin?
Material from atheromatous plaques
debris inserted IV
bits of brain or liver after trauma
Can embolization occur in veins? Why?
No. Blood flow is from smaller to larger vessels
What happens to thrombi formed in veins?
They do not embolise in veins, as venous system is from smaller to larger vessels. They go to the right heart and then embolise in pulmonary arteries
Where do emboli from the left heart or aorta end up?
Anywhere in the systemic circulation especially in lower limbs.
Approximately 80% of pulmonary emboli arise from thrombi in the _____________________ and ________________
deep veins of the thigh and popliteal vein
Large emboli that become lodged astride the bifurcation of an artery blocking both branches are called ______________
Give three reasons why thrombi are often seen in the left heart.
1) Infarcts commonly form on the left ventricle, damaged endothelium encourages thrombi formation and because heart is beating, these thrombi often embolise
2) atrial fibrillation causes decreased atrial contraction, dilation of the left atrium, stagnation of blood and thrombus formation
3) vegetations are more common on the valves of the left heart
What is a "paradoxical emboli"?
Embolisms that form in the systemic veins embolise to the systemic arteries. They bypass the lungs because of an atrial septal defect or an interventricular septum defect OR the arterio-venous anastomoses in the pulmonary circulation when the pressure in the venule is higher than the pressure in the arteriole.
When a young person has an ischaemic stroke, which heart defect might he have?
Patent foramen ovale
Because the patient probably had a paradoxical embolus that caused the stroke
Which is an embolus that goes from the systemic veins to the systemic arteries
Usually occurs due to ASD/VSD
What are transient ischaemic attacks?
Episodes of neurological dysfunction that appear suddenly, last minutes to hours and then disappear. They are the result of microscopic emboli to the brain.
Transient ischaemic attacks usually happen as the result of which 2 kinds of embolism originating from where?
Atheroemboli from carotid arteries
Thromboemboli from the left heart
Why do transient ischaemic attacks not have lasting effects?
Because the emboli are so small that they break up quickly before any damage can be done
Fat emboli can occur after __________
Bone marrow emboli can occur after ________
Scuba divers may experience "the bends" if they resurface too quickly. Why is that?
Under the water, outside pressures are higher than that on land so increased amounts of gas become dissolved in the blood and body tissues. If scuba divers resurface too quickly, then the sudden drop in pressure causes gases to come out of solution and into the body tissues as bubbles (air embolism), causing a huge amount of pain and blocking blood flow.
What are the two things that general prophyaxis of thromboembolic diseases aims to prevent?
Preventing venous stasis
What are the measures used to prevent venous stasis and hence prevent thromboembolic disease?
encourage patients to mobilize early after an operation or illness
elevating legs after an operation
calf muscle stimulation
What measure is used to prevent hypercoagulability and hence prevent thromboembolic disease?
Anticoagulants - aspirin, heparin and warfarin
Name the three anticoagulants that are used to prevent hypercoagulability and hence prevent thromboembolic disease?
aspirin, heparin and warfarin
Warfarin is used as prophylaxis against thrombosis. it is an oral medication which interferes with ____________ metabolism
What is an "infection"?
The introduction of a microorganism into a normally sterile tissue
Differentiate between septicaemia and sepsis
Septicaemia is the presence of a pathogen in the blood which can lead to sepsis
What is the difference between sepsis and severe inflammatory response syndrome (SIRS)?
SIRS is a group of classical clinical signs in response to inflammation. SIRS can be as a result of infection but also as a result of surgery, malignancy, trauma... Sepsis is two or more of these signs but specifically in response to infection.
When does sepsis become severe sepsis?
When there is at least one sign of organ dysfunction (due to organ hypo-perfusion)
What three things determine the size of a cell population? (Hint: all three are RATES...)
Rate of cell proliferation
Rate of cell death by apoptosis
Rate of cell differentiation
_________ regulate normal cell proliferation
What are the four stages of the cell cycle?
M - mitosis - cell divides
S - DNA synthesis
What is the R point (restriction point) in the cell cycle?
most critical checkpoint as the majority of cells that pass the R point will also complete the cell cycle. This is the most commonly altered checkpoint in cancer cells!
What are two proteins that regulate and control the cell cycle?
How do cyclins and cyclin-dependent kinases work to control the cell cycle?
When cyclin binds to CDK, it activates the CDK which then can go on to phosphorylate proteins
What is cell adaptation?
Response by cells to challenges that are not severe enough to cause injury by adaptations that are not pathologic
What are the five ways by which cells can adapt to challenges that are not severe enough to cause injury?
Cell adaptation: What is "regeneration"?
cells multiply to replaces losses. This can be normal (e.g. replacement of RBCs and WBCs by the bone marrow) or can also be after injury.
What two tissues are incapable of regeneration?
Neurones of the CNS
Cell adaptation: What is atrophy?
Cells become smaller
Cell adaptation: What is hypertrophy?
Cells increase in size
Cell adaptation: What is metaplasia?
Cells are placed by a different kind of cell
Cell adaptation: What is hyperplasia?
Cells increase in number above normal
What is an example of normal atrophy of cells in a tissue?
Ovarian atrophy - after menopause
Uterine atrophy - after pregnancy
What are 2 examples of why pathological atrophy of cells in a tissue may occur?
atrophy of disuse - muscle atrophy
inadequate blood supply leading to atrophy
Give 2 examples of pathological atrophy of cells in a tissue
loss of endocrine stimuli
pressure (e.g. due to a tumour)
cerebral atrophy (Alzheimers)
Hypertrophy is the type of cell adaptation that occurs mainly in which kind of tissue (e.g. labile, stable or permanent)?
Give an example of non-pathological hypertrophy
Hypertrophy of skeletal muscle cells in body builders
Give an example of pathological hypertrophy
Compensatory hypertrophy e.g. of one kidney
OR RV hypertrophy
Give an example of metaplasia and state which cell types are being replaced with what.
Barrett's oesophagus (stratified squamous epithelium to gastric glandular epithelium)
Smoker's lung (bronchial pseudostratified ciliated epithelium to stratified squamous epithelium)
Give an example of pathological and non-pathological hyperplasia.
Pathological - eczema - hyperplasia of epidermis
Non-pathological - proliferative endometrium - under influence of oestrogen
What is "aplasia"?
complete failure of a tissue or organ to develop or an organ whose cells ceased to proliferate
What is "dysplasia"?
abnormal maturation of cells within a tissue
What is "involution"?
normal programmed shrinkage of an organ e.g. thymus in early life, uterus after childbirth
What is "hypoplasia"?
congenital underdevelopment or incomplete development of a tissue or organ e.g. testicules in Klinefelter's
People with Klinefelter's have which sex chromosomes?
What is "atresia"?
no orifice, congenital imporforation of an opening e.g. anus/vagina
an abnormal growth of cells that persists after the initial stimulus is removed
What is the similarity and difference between neoplasia and hyperplasia?
SIMILARITY - both cause an increase in the number of cells above normal
DIFFERENCE - hyperplasia is stimulated by growth factors and is reversible whereas neoplasia is caused by genetic alterations and is irreversible
What is a "malignant neoplasia"?
An abnormal growth of cells that persists after the initial stimulus is removed AND it invades surrounding tissue with the potential to spread to different sites
What is the difference between benign and malignant neoplasms?
Benign - remain confined to their site of origin, do not produce metastases
Malignant - does not remain confined to the site of origin, potential to metastasise
Is neoplasm = cancer?
NO! Cancer is a malignant neoplasm.
What is the difference between tumour and neoplasm?
Tumour is any clinically detectable lump or swelling. Neoplasm is only one type of tumour. e.g. it could just be a fluid-filled bursa OR a fibroid
What is a "metastasis"?
Malignant neoplasm that has spread from its original site to a new, non-contiguous site
How do malignant tumours appear to the naked eye?
irregular outer margin
may show areas of necrosis and ulceration if on a surface
How do benign tumours appear to the naked eye?
confined local area
pushing outer margin
What are cells with no resemblance to any tissue called?
What do cells of a benign neoplasm look like under a microscope?
resemble the parent tissue
What do cells of a malignant neoplasm look like under a microscope?
Range from well to poorly differentiated
With worsening differentiation, there is:
increasing nuclear size and nuclear to cytoplasmic ratio
increasing mitotic figures
increasing variation in size and shape of cells and nuclei
increasing nuclear staining
What is pleomorphism, in relation to cells of a malignant neoplasm?
Increasing variation in size and shapes of cells and nuclei
Clinicians use the term _______ to indicate differentiation
A neoplasm emerges from a monoclonal population of mutant cells through a process called _______, which is the accumulation of yet more mutations
How does an expanded, monoclonal population of mutant cells come about from normal cells?
Initiators (mutagenic agents) + promoters (which cause cell proliferation)
What does it mean if a collection of cells is referred to as "monoclonal"?
They all originated from a single founding cell
What two genes do genetic alterations that lead to cancer usually affect?
Tumour suppressor genes
When proto-oncogenes are abnorally activated, what are they then called?
Benign neoplasms usually have what suffix?
Malignant neoplasms usually have what suffix?
-carcinoma (if epithelial malignant) OR
-sarcoma (if stromal malignant)
What is an "adenoma"?
Benign neoplasm of glandular epithelium
What is the difference between an in-situ and an invasive carcinoma?
In-situ - no invasion through epithelial basement membrane
Invasive - penetrates through epithelial basement membrane
What is "leukemia"?
Malignant neoplasm of blood-forming cells arising in the bone marrow
What is "lymphoma"?
Malignant neoplasm of lymphocytes, mainly affecting lymph nodes
What is a "myeloma"?
Malignant neoplasm of plasma cells
In the ovary, what kind of germ cell neoplasm arises from pluripotent cells?
In the testes, what kind of germ cell neoplasm arrives from pleuripotent cells?
Invasion into surrounding tissue by carcinoma cells involves 3 important alterations:
Motility - changes in actin skeleton
Adhesion - altered adhesion between malignant cells and stromal proteins which involves changes in integrin proteins
Stromal proteolysis - cells degrade basement membrane and stroma which involves altered expression of proteases
^ "MASs" like a tumour
Carcinoma cells look more like ________ cells than epithelial cells
Transport of carcinoma cells to distant sites is via 3 routes. Name these 3 routes.
1) Blood vessels
2) lymphatic vessels
3) fluid in body cavities (pleura, pericardial, peritoneal)
Surviving microscopic deposits of malignant cells that fail to grow are called ___________
What is tumour dormancy?
When a seemingly disease-free person harbours many micrometastases
What three factors could cause someone with tumour dormancy to suddenly have their micrometastases to start growing?
Hostile secondary site
Which two factors determine the site of a secondary tumour?
1) regional drainage of blood, lymph and coelomic fluid
2) the "seed and soil" phenomenon - interaction of the malignant cells with their local tumour environment
Give three examples of local effects of primary and secondary neoplasms
direct invasion and destruction of normal tissue
ulceration at a surface leading to bleeding
compression of adjacent structures
blocking tubes and orifices
Give 5 examples of the systemic effects of neoplasms
reduced appetite and weight loss (cachexia)
may produce hormones (e.g. thyroid adenoma produces thyroxine)
skin problems such as pruritis and abnormal pigmentation
Give 3 behavioural and dietary risk factors related to cancer
High body mass index
Low fruit and vegetable intake
Lack of physical activity
Extrinsic carcinogens fall into 3 main categories:
There are 6 classes of mutagenic chemical carcinogens. Name 3 of these classes.
Polycyclic aromatic hydrocarbons
Diverse natural products e.g. asbestos
Procarcinogens are only converted into carcinogens by the ___________________________ enzymes in the liver
What are "complete carcinogens"?
Carcinogens that act as both initiators + promoters
Give an example of a "complete carcinogen"
Radiation can affect DNA directly but also indirectly by generating ____ ________
_________ radiation damages DNA bases and causes single and double strand DNA breaks
e.g. X rays and nuclear radiation
How can some infections be direct carcinogens?
They directly affect the genes that control cell growth
Human Papilloma virus which is strongly linked to ______ carcinoma is a direct carcinogen because it expresses the E6 and E7 proteins that inhibit ___ and ____ proteins both of which are important in cell proliferation.
Human Papilloma virus which is strongly linked to cervical carcinoma is a direct carcinogen because it expresses the E6 and E7 proteins that inhibit p53 and pRB proteins both of which are important in cell proliferation.
How does HIV act indirectly as a carcinogen?
Lowers immunity, allowing other potentially carcinogenic infections to occur
Inherited predisposition to neoplasia can occur through germline mutations. Retinoblastoma has what pattern of inheritence?
The ___________ hypothesis explains why people who are predisposed to certain types of cancer do not always end up acquiring them in their lifetimes.
two hit hypothesis
Two hit hypothesis: For familial cancers, the first "hit" is delivered through the germline and affected all cells in the body. The second hit was a ______________________
Genes that inhibit neoplastic growth are known as _____ __________ _____
tumour suppressor genes
Why are two hits needed in order to inactivate the tumour suppressor genes?
Both alleles need to be mutated and inactivated
Genes that enhance neoplastic growth are known as _______
Are two hits needed in order to activate the oncogenes and hence favour neoplastic growth?
No. Only one hit necessary, one allele activated is enough to enhance neoplastic growth.
Give four things that proto-oncogenes can encode.
Growth factor receptors
Plasma membrane signal transducer
Cell cycle regulator
____________ ____________ is a condition that is due to mutations in one of the 7 genes that affect DNA nucleotide excision repair. Patients with this condition are very sensitive to UV damage and develop skin cancer at a young age.
What is the inheritence pattern of xeroderma pigmentosum?
Heriditary non-polyposis colon cancer syndrome is associated with _______ carcinoma
Heriditary non-polyposis colon cancer syndrome is autosomal dominant and the germline mutation affects what type of gene?
DNA mismatch repair genes
Familial breast carcinoma is associated with which two genes that are important for repairing double strand DNA breaks?
BRCA1 and BRCA2
BRCA1 and BRCA2 are two genes associated with familial breast carcinoma. What is the role of these two genes?
Double strand DNA break repair
A fully evolved malignant neoplasm exhibits six hallmarks of cancer.
Name four of these hallmarks.
1) self-sufficient growth signals
2) resistant to growth stop signals
3) no limit to the number of times the cell can divide
4) sustained ability to induce new blood vessels
5) resistance to apoptosis
6) the ability to invade and produce metastases ---> only malignant
Name three of the most common carcinomas in the UK
In children younger than 14, what are two of the most common cancers?
What is "tumour stage" the measure of?
the malignant neoplasm's overall burden
What is the name of the commonest method for assessing the extent of a tumour?
TNM staging system
In the TNM staging system for staging tumours, what do T, N and M stand for?
T - size of the primary tumour - T1 to T4
N - extent of regional node metastasis / lymphatic spread - N0 to N3
M - extent of distant metastatic spread / spread via blood stream - M0 or M1
Lymphoma has its own staging system. What is the name of this staging system?
Ann Arbor staging
What is the name of the staging system for colorectal carcinoma?
What does tumour grade describe?
the degree of differentiation of a neoplasm
When talking about the grade of a malignant neoplasm, what do G1 and G4 say about the differentiation of the cells of the tumour?
G1 - well-differentiated
G4 - undifferentiated or anaplastic
What is the name of the grading system for breast cancer?
Why is grading a tumour important?
What is the difference between adjuvant and neoadjuvant treatment for a cancer?
Adjuvant - given after surgical removal of a primary tumour
Neoadjuvant - given to reduce the size of a primary tumour prior to surgical excision
How does radiation therapy kill proliferating cells?
Triggers apoptosis OR interferes with mitosis
Targets rapidly dividing cells
Several classes of chemotherapy exist. Name all 4 of these classes
alkylating and platinum based drugs
What is the ONE MAIN difference between chemotherapy and radiotherapy?
chemotherapy is non-specific and radiotherapy is specific (only targets cancer cells)
Give an example of a drug that is used in hormone therapy for breast cancer patients.
How does tamoxifen work to treat malignant breast cancer?
Tamoxifen is a selective oestrogen receptor modulator
It binds to oestrogen receptors
Oestrogen cannot bind to the receptors
So breast cancers don't grow
_______ _________ are used to monitor cancer burden during treatment and follow up.
What are 2 types of tumour markers used to monitor cancer burden during treatment and follow up?
What three kinds of cancers are screened for in the UK?
Give two advantages for performing cytology rather than a biopsy for histology?
Give 2 reasons why a person would be required to have a coroner's autopsy
if the deceased is unknown
if the deceased died in custody
if the deceased was not seen by a doctor within 14 days of death
if the death was a result of a termination of a pregnancy
if the death was a result of an accident
What substance if present in the blood would confirm the presence of a myocardial infarction?
Troponin I or troponin T
Why does troponin get into the blood stream after a myocardial infarction?
Area of cardiac muscle has undergone necrosis due to the lack of blood supply
In necrosis, cell membrane would become leaky and intracellular proteins leak out of cells and can be measured in the blood
Name three conditions in which fatty liver is commonly seen
Excessive alcohol intake
Carbon tetrachloride toxicity
Which two substances accumulate in hepatocytes of patients who drink XS alcohol?
How does cirrhosis appear histologically?
Bands of fibrosis
Surrounding nodules of regenerating hepatocytes
Give 3 examples of opsonins
Give one example of how the body protects itself against free radicals
Antioxidants like vitamins A, C and E donate an electron to a free radical thus neutralising it
What is a "free radical"?
Reactive oxygen species / Molecules with a single unpaired electron in the outer orbit
What is "chemotaxis"?
Directional movement towards or away from a chemical attractant
What is "diapedesis", which is used by neutrophils in acute inflammation?
passage of blood cells through intact blood vessel walls
Give an example of a chemoattractant.
fibrin degradation product
How is an ulcer in the GI tract defined?
Breach in the lining of the bowel to the level of the submucosa or deeper
What are the two classical histological features of Crohn's disease?
Presence of granulomas
Give two features seen at colonoscopy that are typical of Crohn's disease.
cobblestone appearance to bowel mucosa
involvement of the ileum
What's the difference between ulcerative colitis and Crohn's disease?
Ulcerative colitis affects only the mucosal layer of the large intestine. It is continuous inflammation.
In Crohn's disease, inflammation can appear anywhere in the digestive tract, from the mouth to the anus. And it generally affects all the layers of the bowel walls, not just the inner lining. It can appear as patches of inflammation unlike UC.
People with ulcerative colitis and Crohn's disease often develop red marks just below the skin surface, particularly on their shins. What is this condition called?
What are abdominal adhesions?
Bands of fibrous tissue that form between abdominal tissues and organs
A 21 year old woman is admitted to hospital after having taken 25g of paracetamol 2 days earlier. Why is her alanine aminotransferase high?
Hepatocytes died as a result of paracetamol toxicity and ALT leaked out of the damaged cell membranes of these cells
Which drug raises the PT and is monitored by regular INR measurements?