General Study Flashcards
Define “Pathophysiology”
The “What”
The physiology behind observed pathological changes.
Define “Pathogenesis/Aetology”
The “Why”
The causal factors of diseases.
Disease is the manifestation of _____ _______.
Cell injury.
Define “Parenchyma”
Specialist cells of a specific organ.
e.g., myocardium in the heart.
Define “Stroma”
The network of connective tissue that acts as scaffolding for parenchyma.
Made of collagen and fibroblasts.
Define “Endothelial Cells”
Parenchyma cells that line the internal walls of blood vessels.
Define “Epithelial Cells”
Parenchyma cells that line the internal walls of organs other than blood vessels.
Define “Atrophy”
The reduction in cell size and function.
Define “Hypertrophy”
The increase in cell size and output.
Define “Hyperplasia”
The increased number of cells.
Define “Metaplasia”
Changes in cell morphology and function.
The cells are still recognisable, however, they are starting to look different and struggle to function.
Define “Dysplasia”
The increased number, change of morphology, and differentiation of cells.
Pre-neoplastic.
What cells produce mucus?
Goblet cells
What chemicals are released when a cell dies?
Lysosomes.
What chemical is released when endothelial cells are damaged?
Nitrous Oxide (NO)
What are “Lysosomes”?
Digestive enzymes.
What is the cellular effect of ischemia that leads to cell dysfunction and death?
The lack of oxygen restricts the cell’s ability to metabolise ATP within the mitochondria. This causes dysfunction of sodium-potassium pumps which require ATP to function. This leads to cell swelling due to water invasion within the cell. If swelling continues, the cell will burst.
What results from mechanical damage to a cell (i.e., mechanical damage to the cellular membrane)?
When the cell membrane is torn apart, extracellular ions (specifically calcium) invade the cell. This causes the release of enzymes, creating reactive oxygen species of free radicals that can lead to mitochondrial dysfunction.
How do O2 free radicals cause damage within cells?
A free radical is a molecule with an electron removed. As these move around a cell, they rip electrons from other molecules and structures and cause internal damage within the cell.
A) Which version of cell death results in inflammation, and B) why does this not occur with the other form?
A) Necrosis.
B) This does not occur with apoptosis as this includes the use of vesicles which remove the cellular debris and use enzymes to clean the area without inflammation.
What are the cardinal signs of inflammation?
- Swelling
- Heat
- Redness
- Pain
- Loss of function
What are the three main constituents of blood?
- Plasma
- Red blood cells
- White blood cells
What percentage of blood volume is A) plasma, and B) formed elements?
A) 55%
B) 45%
What three constituents of blood volume are categorised as “Formed Elements”
- Platelets
- Leukocytes
- Erythrocytes
what percentage of plasma volume is made from A) protein, B) water, and C) other solutes?
A) 6%
B) 92%
C) 2%
What percentage of blood’s formed elements are made from A) platelets, B) leukocytes, and C) erythrocytes?
A) 3-5%
B) 0.1-0.2%
C) 94-96%
What are the five cell types categorised as leukocytes?
- Neutrophils
- Lymphocytes
- Monocytes
- Eosinophils
- Basophils
What are the two broad categories of leukocytes?
- Lymphocytes
- Innate immunity
What are the three durations of inflammation and what are their periods?
- Acute: the first few hours to several days.
- Subacute: up to 10-14 days.
- Chronic: >2 weeks (3-moths for pain)
What are the three stages of the vascular process in the acute inflammation response?
- Vasoconstriction
- Vasodilation
- Increased permeability
What triggers the “Pain” aspect of inflammation’s cardinal signs?
Sensitisation of nociceptors.
Briefly outline the vascular processes of the acute inflammation response.
- Vasoconstriction occurs to limit immediate bleeding.
- Vasodilation occurs in response to NO release from damaged endothelium
- This floods the site with blood and cellular components resulting in heat and redness of the area.
- This increases blood flow and causes transudate permeation and localised swelling.
- Increased permeability occurs which also coincides with increased stickiness of endothelium and increased permeability specifically to WBC - exudate (this also contributes to swelling).
Briefly outline the cellular processes of the acute inflammation response.
- Neutrophils initially respond to cellular damage in the form of MMP (which indiscriminately breaks down cells within the affected area) and Enzymes (which break down the constituents of the cellular components).
- Macrophages then clean up cellular debris via phagocytosis and are dominant at 24 hours.
- Fibroblasts then begin early repair by laying down collagen.
What are the two main initial products of macrophages?
- MMPs (Matrix Metalloproteinases)
- Enzymes.
What is the other name for Macrophages?
Monocytes.
Define “Suppuration”
The formation and accumulation of dead material.
If this occurs in a contained area, an abscess or pimple is formed.
If this occurs internally, the lymphatic system will reabsorb this.
What are the four possible outcomes of acute inflammation and what conditions determine these?
- Resolution and return to homeostasis.
- If there is slight tissue damage or the removal of the causal agent. - Healing by scarring.
- If there is substantial tissue damage, it occurs in non-regenerative tissue, or there is excessive fibrin exudate. - Formation of an abscess.
- If there is excessive tissue damage (necrosis) and bacterial or fungal inflection. - Chronic inflammation.
- If tissue damage is persistent.
Excessive fibrosis can result in a loss of _________.
Function
Chronic inflammation is classed as _____cellular due to the _________ number and _______ of cells that react and are involved.
A) Hypercellular
B) Increased
C) Type
During chronic inflammation, is there an increase or decrease in Neutrophil activity compared to acute inflammation?
Decreased
During chronic inflammation, is there an increase or decrease in Macrophage activity compared to acute inflammation?
Increased
During chronic inflammation, is there an increase or decrease in T and B Cell activity compared to acute inflammation?
Increased
During chronic inflammation, is there an increase or decrease in Fibroblast activity compared to acute inflammation?
Increased
What is the main action of T Cells in chronic inflammation?
Killer T Cells attack, destroy and ingest agents.
Helper T Cells release chemical mediators to bring other cells into the area.
What is the main action of B Cells in chronic inflammation?
Coat the pathogens in an immune complex.
What are the 7 key steps in the macrophages’ process in chronic inflammation?
- Macrophages are attracted to the site via chemotaxis.
- They then proliferate at the injury site.
- Phagocytosis begins.
- Macrophages release lysosomal enzymes to dissolve the tissues.
- This causes the release of reactive oxygen species incurring damage within cells.
- This results in the release of cytokines.
- The release of MMPs is triggered which breaks down surrounding tissue.
B Cells and T Cells are types of what classification of cells?
Lymphocytes
What type of cells are Cytokines?
Chemical Mediators
__________ (cell type) migration leads to the activation of endothelial cells which causes _______ during the inflammation process.
A) Lymphocyte
B) Adhesion
_________ and Helper T Cells kill targeted cells and cause the release of more _________ to bring more cells to the injured area during the inflammation process.
A) Cytotoxic
B) Cytokines
B Cells create _________ that coat the pathogen and create an _________ ________ to flag cells for destruction during the inflammation process. This is a __________________ response.
A) Antibodies
B) Immune complex
C) Pro-inflammatory
In chronic inflammation, macrophages become _______________. These are known as ____ macrophages.
A) Pro-inflammatory
B) M1
In chronic inflammation, M1 macrophages produce pro-inflammatory ___________ and _________.
A) Cytokines
B) ROS
What is angiogenesis and what signals this to occur in chronic inflammation?
A) The growth of new blood vessels.
B) The release of growth factors by macrophages.
The deleterious effects of chronic inflammation are mostly due to the damage of what two cell types within the affected area?
A) Parenchyma
B) Stroma
Define the following terms in the context of inflammation and repair:
A) Regeneration
B) Replacement
A) Regrowth of parenchymal cells of the same tissue type.
B) The replacement of cells by connective tissue, namely collagen. This results in scar tissue.
What are the three main cell types regarding regenerating and replacing damaged cells?
- Labile Cells
- Stable Cells
- Permanent Cells
What are the regenerative qualities of:
A) Labile Cells
B) Stable Cells
C) Permanent Cells?
A) Proliferate throughout life.
B) Low level of normal replication but can be regenerated after injury.
C) Non-regenerative.
A fracture is the ___________ of a bone.
Discontinuity
what type of fracture often occurs after a child sustains a FOOSH-related injury?
A buckle fracture.
What are the seven types of common fractures?
- Transverse – non-displaced
- Transverse – displaced
- Compound
- Oblique
- Comminuted - multiple pieces
- Greenstick - children (also buckle)
- Spiral
What other injuries should be considered with a displaced or compound fracture?
Damage to other tissues such as muscle, aponeurosis, skin, blood vessels, nerves, tendons, and ligaments.
_____________, using acute inflammatory response to get to the site of injury, clear dead cells/tissue and debris to set the scene for healing to begin.
Leucocytes
What is the correct term for compact bone?
Cortical bone tissue
What are the two correct terms for spongy bone?
- Trabecular and
- Cancellous bone tissue
What is the name of the outer layer of bone tissue?
Periosteum.
Does the periosteum have a large or small amount of vascularization and nociception?
The periosteum has a large amount of vascularization and nociception.
What are Haversian and Volkmann canals?
Haversian canals are cylindrical structures within cortical bone tissue that longitudinally allow blood vessels, nerves, and lymph vessels to provide nutrients to the bone.
Volkmann canals run perpendicular or oblique within bone tissue, connecting Haversian canals and moving nutrients from the periosteum to deeper bone layers.
What is the main difference between bone healing compared to soft tissue healing?
Bone can almost completely heal.
What are the four stages of bone healing and what are their general timelines?
- Inflammation and haematoma - 0-3 days
- Soft callus - 2-3 weeks
3a. Hard callus stage 1 - end of week 4
3b. Hard callus stage 2 - 1-3 months - Remodelling - 3-12 months
What is the surgical procedure that results in primary intention healing in bone tissue?
Open Reduction and Internal Fixation (ORIF)
What are the benefits and restrictions of ORIF?
Benefits:
- Able to move early
- Gains strength with mobilisation
Restrictions:
- Does not heal as strong
- relies on external fixation for strength
What can occur if a fracture is not immobilised appropriately and why does this occur?
Pseudoarthrosis.
This occurs when a fracture is not allowed to heal which results in cartilage being laid in the fracture site instead of bone.
At what age bracket is bone mass at its peak?
16-25 years old.
What are the four main influences on bone mass?
- Nutritional factors
- Genetic influences
- Hormonal factors
- Exercise and environmental factors
Define Osteoporosis.
An increased porosity of the skeleton which results in weakened bones with subsequent fracture risk.
What percentage of bone turnover occurs in cortical and cancellous bone in adults?
Cortical - 20%
Cancellous - 80%
___% of patients (aged in their 80’s) who were admitted with an ____________ hip fracture were dead within __________ – of various causes.
A) 33%
B) Osteoporotic
C) 12-months
A) Where does the right side of the heart pump blood?
B) What vessel does this occur through?
A) The lungs.
B) The pulmonary artery.
A) Where does the left side of the heart pump blood?
B) What vessel does this occur through?
A) The body.
B) The aorta.
What is the name of the endothelium of the heart?
Endocardium
What is the name of the parenchyma of the heart?
Myocardium
What are the two layers of serious pericardium?
Visceral and parietal.
What is the most superficial layer of cardiac tissue called?
Pericardium.
What is the pericardium primarily made from?
Fibrous collagen.
What is the formula for Blood Pressure?
BP = Q x TPR
(Blood Pressure = Cardiac Output x TOtal Peripheral Resistance)
When reading BP measurements, which number is diastolic and systolic?
Diastolic is the second and lowest number while systolic is the first and highest.
What are the five factors that influence peripheral resistance of blood vessels?
- Length of pipes
- Diameter of pipes
- Blood volume
- Blood viscosity
- Vessel stiffness/compliance.
What is the formula for cardiac output (Q)?
Q = SV x HR
(Cardiac output = stroke volume x heart rate)
What is the average stroke volume for an adult?
~70mL
What are the three main factors that affect cardiac output (Q)?
- Fluid volume
- Increased venous return
- Increased contractility
Explain the Renin-Angiotensin-Aldosterone System (RAAS) pathway and the two main “end states” of it.
Liver –> Angiotensinogen
Kidney –> Renin
Renin + Angiotensinogen –> Angiotensin I
Lung –> ACE (Angiotensin Converting Enzyme)
ACE + Angiotensin I –> Angiotensin II
Angiotensin II –> Vasoconstriction (end state 1)
Angiotensin II + Adrenal gland –> Aldosterone
Aldosterone –> NaCl and H2O Reabsorption (end state 2).
What is NaCl?
Sodium Chloride
Blood flow to an organ is __________ linked to the resistance to blood flow. This means that _________ resistance results in ________ flow at the organ.
A) Inversely
B) High
C) Low
Secondary hypertension is generally due to disease in what organ?
Kidney
What are the six main causes of Hypertension?
- Genetics
- Aging
- Kidney issues
- Hyperinsulinemia/hyperglycaemia
- Inflammation
- Obesity
What percentage of CO goes to the kidneys?
20%
What is the rate of blood flow through the kidneys per minute?
1.2L/min
What is the name of the organ within the kidney that senses renal blood flow in and around the glomerulus?
Juxtaglomerular Apparatus
How does chronic hypertension affect the juxtaglomerular apparatus?
Chronic hypertension results in a decrease in blood flow through the kidneys. This triggers the juxtaglomerular apparatus to adjust the blood pressure and flow constantly. This puts excessive stress on the RAAS and blood vessels.
What does ACE stand for?
Angiotensin Converting Enzyme
What is the main function of Angiotensin II?
It is a strong vasoconstrictor.
Describe the chain of events that Angiotensin II causes via the adrenal cortex resulting in increased blood volume.
- Angiotensin II stimulates the adrenal cortex to release Aldosterone.
- Aldosterone acts on the distal convoluted tubules and collecting ducts of the kidneys, increasing sodium reabsorption.
- Water follows sodium which in turn increases blood volume.
Describe the chain of events that Angiotensin II causes via the hypothalamus resulting in increased blood volume.
- Angiotensin II stimulates the hypothalamus to release Antidiuretic Hormone.
- This increases water reabsorption which decreases urine output.
- More fluid retention results in increased blood volume.
What are the three pathways through which Angiotensin II increases blood pressure?
- It stimulates the hypothalamus to produce antidiuretic hormone reducing urine output.
- It stimulates the adrenal cortex to release aldosterone increasing sodium reabsorption in the kidneys and, therefore, water volume, elevating blood volume.
- It causes vasoconstriction which directly increases blood pressure.
What is the pathophysiological pathway of myocardial infarction through to its end state?
Myocardial infarction –>
Ischemic cell death –>
Necrosis –>
Inflammation –>
Fibrosis of myocardium –>
Due to its non-contractile nature, this scar tissue cannot perform normal heart functions resulting in a loss of heart capacity.
Why is there such a high risk of reoccurrence of myocardial infarctions?
Because the risk factor(s) are often still present.
e.g., atherosclerosis, high BP, etc.
What are the five main causes of heart failure?
- Myocardial infarction
- Post viral infection
- Secondary chronic overload hypertension (caused by another medical condition)
- Volume overload (RAAS) (expansion of the extracellular fluid volume)
- Other ventricle disorders and congenital abnormalities.
What is Afterload?
The amount of resistance the heart must overcome to open the aortic valve and push the blood volume out into the systemic circulation.
What is Preload?
The load on the heart that is created by the volume of blood received into the left ventricle from the left atrium (at the end of ventricular diastole) and that it must eject with each contraction.
A) What are the four most common drugs used to treat hypertension and heart failure?
B) How do these work?
- ACE Inhibitors:
- They reduce the effects of angiotensin II (vasoconstriction, Na retention, and aldosterone release) - Beta Blockers:
- Reduce HR and cardiac contractility to reduce Q and decrease the demands on the heart. - Diuretics:
- Decreases blood volume by promoting urine output. - Anticoagulants:
- Decreases the risk of clotting cause by blood stasis.
