Tutorials Flashcards
Name 4 core areas of pathophysiology and how they assist understanding disease processes?
Aetiology
Molecular response
Morphological changes (macro, micro)
Clinical representation (signs, symptoms)
Give a summary of myocardial infarction and the 4 areas of patho
- Generally acquired - lifestyle (sedentary), risk factors (High cholesterol), DM, Hypertension, smoking
- Stress on blood vessel, plaque formation -> stable angina, plaque rupture
- Micro: occlusion to blood vessel; blockage; necrosis
Macro: loss of vascularisation; pale - Unstable angina; radiates to limbs, SOB, indigestion, sweating, pallor, fatigue
What are the 5 leading world-wide causes of death?
How could we prevent them
Ischemic Heart Disease Cerebrovascular disease Lower respiratory infection HIV/AIDS COPD
IHD: diet, smoking, low stress, exercise
Name one condition we should research more into now to prevent in 20 years time?
Cardiovascular Disease
1 in 4 deaths in Australia
Causes; unhealthy diet, inactivity, smoking, alcohol
Symptoms: chest pain, SOB, numbness upper body
What is the average life expectancy of non-indigenous Australians and First Australians?
Leading causes of deaths?
Males - 71.6 yrs
Females 75.6
Increased by 2.5 years and 1/9 years since 2010 - 2012
Coronary artery disease Stroke - 2x RHD DM - 3.4 times higher preve Cancer
Describe some physiological and pathological forms of hypertrophy and atrophy
Pathological Hypertrophy:
- thickening of heart muscle
- decrease in chamber sizes in heart
- reduced capacity of heart to pump blood out
Mechanism of hypertrophy:
- stretch induces growth factors and protein synthesis
Physiological atrophy:
- muscle atrophy due to less utilisation
Pathological atrophy:
- result of cellular injury (starvation, disease, dying, ageing)
Describe cell morphology (shape) during apoptosis and necrosis
The first stage of necrosis involves swelling of the ER and mitochondria, increase the overall cell size. This stage is reversible and able to be returned to normal cell morphology. If insult/injury progresses, the cell membrane will begin to breakdown causing blebbing. The leakage of cell contents triggers and inflammatory response.
List the four main clinical presentations of necrosis and conditions which may cause each
- coagulative
- heart (ischemia, MI)
- firm, maintained after cell death - Liquifactive
- hypoxia (brain)
- creamy yellow pus - Caseous
- tuberculosis (lungs)
- white, soft, cheesy - Gangrenous
- peripheral limbs
- lack of oxygen (DM)
- black skin, putrefaction
What are the two main pathways of apoptosis ?
Intrinsic: cell injury—> bcl-2 family sensor—> bcl-2 family effector bax, bak—>mitochondria leaks cytochrome c and pro-apoptotic protein—>initiator caspase—> executioner caspases —> cell death
Extrinsic: receptor-ligand interaction -> receptor —> adaptor protein —> inhibitor caspases —> executioner caspases —> endocnuclease activation, cytoskeleton breakdown —> cell death
hy do you think apoptosis does not result in an inflammatory response?
Apoptosis causes cellular shrinking and fragmentation and intracellular organelles are packed in apoptotic bodies and engulfed by phagocyte without releasing any intracellular substance outside, thus no stimulus for inflammation
During apoptosis, the cell membrane remains intact and the cell breaks into apoptotic bodies, which are phagocytosed
List the most common intracellular accumulations
Normal
- water
- lipids
- proteins
- electrolytes
Abnormal
- infectious agents
- synthesis/metabolism
- indigestable materials (silica, carbon)
- infectious agents (virus)
- synthesis ( triglycerides (lipid accumulation), proteins (defective genes producing defective proteins)
How are intracellular accumulations formed and detected?
- Accumulations of normal cellular constituents – prolonged high intake of water, electrolytes (these get pulled into the cell)
- Accumulations of substances are formed from chronic exposure (pollution, workplace, etc.)
- Accumulations of infectious agents are formed from exposure to infectious agents (skin-to-skin contact, droplets)
- Accumulations of synthesised/metabolised macromolecules can be due to synthesis of defective proteins, decreased metabolic function (eg. alcohol causes liver damage, ability of liver to metabolise lipids
How do we detect accumulations?
Macro
Micro
Detecting Fatty Liver includes clinical testing which would reveal a high cholesterol and high LDL. The lipoprotein accumulation is formed when the balance of lipid catabolism and lipid accumulation is disturbed.
Microscopically, presence of lipoproteins in the liver can be seen in the form of clear vacuoles surrounding the hepatocytes
Macroscopically, the liver would be pale (consolidated white lipid deposits), larger and mild discomfort would be cause by inflammation. There may also be apparent cell rupture/necrosis.
Symptoms may also include Jaundice due to the inability for bilirubin to be remove via bile ducts, which may be blocked from the inflammation.
Define Transudate
The fluid from the blood vessel into the interstitual space. Generally contains water, ions (no proteins), no inflammation
Describe exudate
Escape of fluid that leaks out of blood vessels to other tissues/interstitial fluid
Fluid containshigh protein (fibrin, albumin), cellular debris, inflammatory cells, from high specific gravity blood
Occurs in late inflammation
E.g. Pus
Describe extravastion
The leakage of plasma fluid and proteins through the widened interndothelial spaces into the tissues (the widened interdothelial spaces results in icnreased vascular permeability allowing larger molecules to pass out of the blood vessel)
Leads to oedema
Caused by acute inflammation/vasodilation
Describe chemotaxis
Locomotion (movement) along a chemical gradient
Describe how neutrophils and macrophages (and other cells involved in inflammation) might be assessed from biopsy/tissue sections
Staining in Histopathology such as:
• H&E staining will stain nucleus purple while cytoplasm/proteins pink
Wright’s stain
What are the main differences in the appearance of neutrophils and macrophages (in terms of the time of infiltration and visual appearance/use drawings/images)
Neutrophils only last 24 hours before macrophages come in. Neutrophils are smaller compared to macrophage. Their nuclei have 2-5 lobules and stained dark purple. They are more abundant so really easy to spot under the microscope.
Macrophages change from monocytes once they leave the blood, resulting in structural change. They then engulf foreign bodies creating vesicle in the cytoplasm.
Beyond the completion of a tissue biopsy, what other techniques can be employed to detect different white blood cell populations in the human body?
Haematology would use Blood film analysis to identify morphological features and full blood count.
• Leishman’s (Romanowski) stain - Eosin and Methylene blue dissolved in methanol.
Broadly describe the processes involved in inflammation. Relate these and name the four cardinal signs that might alert you to acute injury and infection.
• - Tissue injury –> vasodilation –> increased blood flow –> redness, heat, erythema
• - Vasodilation –> increased vascular permeability—> allows plasma proteins and leukocytes to leak from blood vessels –> swelling + oedema
• - Leukocyte (neutrophil) recruitment (loose attachment + rolling) —> increased blood flow in site of inflammation - increased blood flow and vascular permeability results in influx of leukocytes into the tissue –> leukocyte proliferation
• - Past 24 hours –> systemic response (eg. Fever, sweating, shivering), neutrophils replaced by monocytes
rolly poly bois
4 cardinal signs: • Redness (rubor) • Heat (calor) • Swelling (tumor) Local pain (dolor)
Name the four cardinal signs
4 cardinal signs: • Redness (rubor) • Heat (calor) • Swelling (tumor) Local pain (dolor)
Define the Systemic Inflammatory Response Syndrome (SIRS) and its presentation. How does this differ from the acute cardinal signs of acute inflammation above? Provide some examples of conditions/situations that might be associated with a SIRS response.
• Severe localised acute inflammation
• LPS (lipopolysaccharide) recognition –> cytokines released and circulate systemically
○ Fever results in response to infection: cytokines (IL1 + TNF) induces:
§ Arachidonic acid (prostaglandin synthesis) metabolism
§ Protein synthesis increases (in liver):
□ C reactive protein (CRP)
□ Fibrinogen
□ Serum amyloid A (SAA)
○ Leukocytosis: > 20000 cells in blood cell counts
§ Caused by accelerated release of leukocytes from marrow
□ Bacterial infections: neutrophilia
□ Viral infections: lymphocytosis
○ Increase in pulse, BP and decreased sweating to maintain pressure & minimise heat loss
○ Eg. Sepsis in severe cases: massive increase in LPS and IL-1 –> vascular coagulation + decreased BP –> vascular failure + metabolic disturbances
Difference – response consists of the same cardinal symptoms but more exaggerated, systemic rather than localised
Explain the processes in acute inflammation
Acute inflammation triggers a healing process including rubor (redness), calor (heat), dallor (pain), and tumor (swelling) immediate onset
• Causes: short term physiological stress
• Dominant leukocyte: Neutrophils
• The microbial agent/damaged cell is eliminated through macrophage apoptosis and out via the lymphatic system
• Morphology: erythema, swelling, neutrophils
End result: elimination of stimulus and return of normal function
