Tutorials

Question 1

Name 4 core areas of pathophysiology and how they assist understanding disease processes?

Answer 1

Aetiology
Molecular response
Morphological changes (macro, micro)
Clinical representation (signs, symptoms)

Question 2

Give a summary of myocardial infarction and the 4 areas of patho

Answer 2

1. Generally acquired - lifestyle (sedentary), risk factors (High cholesterol), DM, Hypertension, smoking
2. Stress on blood vessel, plaque formation -> stable angina, plaque rupture
3. Micro: occlusion to blood vessel; blockage; necrosis
   Macro: loss of vascularisation; pale
4. Unstable angina; radiates to limbs, SOB, indigestion, sweating, pallor, fatigue

Question 3

What are the 5 leading world-wide causes of death?

How could we prevent them

Answer 3

Ischemic Heart Disease
Cerebrovascular disease
Lower respiratory infection
HIV/AIDS
COPD

IHD: diet, smoking, low stress, exercise

Question 4

Name one condition we should research more into now to prevent in 20 years time?

Answer 4

Cardiovascular Disease
1 in 4 deaths in Australia
Causes; unhealthy diet, inactivity, smoking, alcohol

Symptoms: chest pain, SOB, numbness upper body

Question 5

What is the average life expectancy of non-indigenous Australians and First Australians?

Leading causes of deaths?

Answer 5

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

Question 6

Describe some physiological and pathological forms of hypertrophy and atrophy

Answer 6

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)

Question 7

Describe cell morphology (shape) during apoptosis and necrosis

Answer 7

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.

Question 8

List the four main clinical presentations of necrosis and conditions which may cause each

Answer 8

1. coagulative
   - heart (ischemia, MI)
   - firm, maintained after cell death
2. Liquifactive
   - hypoxia (brain)
   - creamy yellow pus
3. Caseous
   - tuberculosis (lungs)
   - white, soft, cheesy
4. Gangrenous
   - peripheral limbs
   - lack of oxygen (DM)
   - black skin, putrefaction

Question 9

What are the two main pathways of apoptosis ?

Answer 9

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

Question 10

hy do you think apoptosis does not result in an inflammatory response?

Answer 10

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

Question 11

List the most common intracellular accumulations

Answer 11

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)

Question 12

How are intracellular accumulations formed and detected?

Answer 12

• 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

Question 13

How do we detect accumulations?
Macro
Micro

Answer 13

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.

Question 14

Define Transudate

Answer 14

The fluid from the blood vessel into the interstitual space. Generally contains water, ions (no proteins), no inflammation

Question 15

Describe exudate

Answer 15

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

Question 16

Describe extravastion

Answer 16

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

Question 17

Describe chemotaxis

Answer 17

Locomotion (movement) along a chemical gradient

Question 18

Describe how neutrophils and macrophages (and other cells involved in inflammation) might be assessed from biopsy/tissue sections

Answer 18

Staining in Histopathology such as:
• H&E staining will stain nucleus purple while cytoplasm/proteins pink
Wright’s stain

Question 19

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)

Answer 19

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.

Question 20

Beyond the completion of a tissue biopsy, what other techniques can be employed to detect different white blood cell populations in the human body?

Answer 20

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.

Question 21

Broadly describe the processes involved in inflammation. Relate these and name the four cardinal signs that might alert you to acute injury and infection.

Answer 21

• - 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)

Question 22

Name the four cardinal signs

Answer 22

4 cardinal signs: 
• Redness (rubor) 
• Heat (calor) 
• Swelling (tumor) 
Local pain (dolor)

Question 23

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.

Answer 23

• 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

Question 24

Explain the processes in acute inflammation

Answer 24

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

Question 25

Explain the processes involved in Chronic inflammation

Answer 25

Chronic inflammation surpasses the healing process with no presentation of the cardinal signs and progressive loss of cell/tissue function, delayed onset
• Causes: long term exposure, mycobacterial (tuberculosis), virus, fungus, parasites, autoimmune diseases or prolonged exposure to toxins
• Morphology: no oedema, tissue destruction, fibrosis and granuloma formation
• Dominant leukocyte: macrophages
• Macrophage accumulation
• Excessive prolonged damage
• End result: fibrosis and loss of function eg. tissue damage in atherosclerosis, rheumatoid arthritis, pulmonary fibrosis, tuberculosis

Question 26

What common systemic blood markers of inflammation exist and what do they represent/measure?

Answer 26

• Erythrocyte sedimentation rate (ESR),
○ The distance red blood cells fall in a test tube in one hour – further decent greater inflammatory response of immune system

• C-reactive protein (CRP) and
○ Level of CRP in blood, CRP is made by the liver, sent into bloodstream for inflammation to protect tissues from infection
○ It is used to detect the severity of inflammation/ whether you’re responding to treatment