Week 2: Cell death and adaptation workshop Flashcards
What are the features in reversible cell injury?
Cellular swelling - small clear vacuoles may appear within the cytoplasm due to degeneration of the ER, more eosinophilic cytoplasm
Cell membrane changes- blebbing or loss of microvilli
Fat accumulation -typically in the liver
Mictochondrial swelling
Nuclear alterations - clumping of chromatin
What are the key morpholigical features of necrosis?
Darker staining cytoplasm
Vacuolated /moth eaten cytoplasm after enzymes have digested the cellular content
Discontinous plasma membrane
Calcium precipitates
Nucleus may shrink and darken or fragment or lighten
What are the cellular features of necrosis?
Swelling
Nucleus - pyknosis (condense), karyorrhexis (fragments), karyolysis (fades)
Plasma membrane is disrupted
Cellular contents, undergoes enzymatic digestion may leaks out of cell
What are the cellular features of apoptosis?
Shrinkage
Nucleus fragments
Plasma membrane is intact but has an altered structure
Cellular content is intact and released within apoptopic bodies
What are the signs of early ischemic damage in an MI?
(still reversible)
Cell nucleus is still present
Cells are lighter staining - reduction in sarcomeres
Patchy appearance
Cell swelling
What are the signs of coagulative necrosis in cardiacmyocytes in MI?
Lack of nucleus
Darker staining cytoplasm
No cellular content is visible
Define myocardial infarction
Death of cardiac muscle due to severe prolonged ischemic conditions
What are the primary diagnostic tests for MI?
ECG
Followed by serum cardiac enzymes
What are the normal serum cardiac enzymes that are tested for in a suspected MI?
What is their normal value?
Troponin 1 <0.03ng/mL
Troponin T <0.1ng/L
Creatine kinase MB isoenzyme <10mg/mL
When and what gross changes occur after an MI?
Visible ater 12hrs
Dark Mottling develops to a yellow core eventually becoming a scar
What is the time span of histological changes in MI?
take 6 to 12 hours to develop
- coagulative necrosis
- neutrophil influx after 12 to 24 hours
- loss of nuclei on day 1 to 3
-phagocytosis on day 3 to 7
- scar forms in 2 months
What is the primary goal in an MI patient?
Manage as soon as possible
What is the cause of cell injury in an MI?
Coronary artery occlusion leading to severe hypoxia and prolonged ischemic conditions for group of cardiac myocytes
Leads to inhibition of myocardial contractility - causing MI
Eventually tissue dies
Why is troponin T the most valued serum cardiac enzyme?
When cardiac myocytes are damaged is released through porous cell membrane
Is the most specific and sensitive for MI.
Can be detected after 2 hours
Is proportional to the degree of damage
What are the potential complications of acute MI?
Arrhythmias
Hypotension
Ventricular septal rupture
Left ventricular free wall rupture
Left ventricular aneurysm formation
What are the aims of percutaneous coronary intervention?
May be described as an angiogram and stent
Is a non-surgical intervention, by which a catheter is used to insert a stent into a narrowed coronary artery
Inflation of the stent widens the vessel helping to treat atherosclerosis, reducing the risk of MI by improving blood flow.
Explain how pyrexia and raised white blood cell count may be related by MI?
Area of inflammation - response to necrotic tissue, recruitement of immune cells, acitvated immune cells may secrete pyrogenes causing fever
CRP is associated with inflammation and the formation of atherosclerosis - is elevated after MI along with fever.
Inflammation is implicated in the pathogenesis of atherosclerosis and acute conronary syndromes
Inwards migration of wbcs
What are the outcomes of MI 12 weeks later?
Disturbance in rate, rhythm and conduction
Pericarditis
Ventricular Septal defect
Ruptured Papillary muscles
Dressler’s Syndrome - autoimmune reaction to myocardial neo-antigens
What are some of the physiological purposes of apoptosis?
Endometrium - shedding of lining for menses
Embryogenesis - elimination of cells and tissues, prevent webbing in fingers and toes
Viral infections - eliminate infected cells
Normal lining epithelial cells (intesintal) - apoptosis to replace and regenerate the GIT lining
What is the key difference between apoptosis and necrosis?
Apoptosis - pre-defined cell suicide, that is executed in a controlled way by an enzyme cascade. Physiological
Necrosis - uncontrolled cell death, no specific enzyme pathway or plan, pathological, has a negative effect on function
What are some of the signs of acute kidney injury on imaging?
Micrscopic: pale swelling cells
Macroscopic - pale and enlarged kidney
What is measured in a liver function test? How do the values change in liver damage?
ALT and AST - increase
Bilirubin - increase
Albumin - decrease (found normally in the blood is a protein produced by the liver)
Alkaline phosphate and y-glutamyltransferase: increase
What are the cellular targets of cell injury?
- Cell membrane damage - resulting in H20 influx
- Mitochondrial damage resulting in Cytochomr C release
- Na+k+ pump damage - cell swelling
- Increased ROS - damage DNA, protein and lipids
- Protein misfolding and DNA damage - activates pro-apoptopic proteins
What plasma elevation is a marker of kidney damage?
Creatinine
Urea
What plasma elevation is a sign of muscle damage?
Creatine Kinase
Myoglobin
What are some of the histological changes that occur in Alcoholic Liver Disease?
Lipids droplets accumulate in heptocytes, push nucleus to the periphery, result in pale white nucleus.
Other cells maintain a central nucleus, but appear a patchy white, may be from ER dysfunction, hepatocyte ballooning - sign of necrosis
Is Alcoholic Liver Disease reversible?
At early stage yes - if the reversible stimuli is removed.
Also recommend maintaining a healthy weight and managing diabetes (if applicable)
If reverse all histological changes would revert to normal
What cellular changes occur in the liver as a result of severe continued alcohol use?
Loss of hepatocytes - replaced by fibrotic tissue
Cirrhosis
Acute liver failure
Hepatocellular carcinoma
What are the gross changes in a cirrhotic liver compared to a normal liver?
Loss of smooth surface - growth on cirrhotic liver nodules on the external and internal surface.
Increased yellowing of colour
Fibrosis of liver tissue
What are the common histological changes in a cirrhotic liver?
Increased fibrous tissue deposition around hepatocyte nodules
Chronic inflammation results in excessive collagen production by hepatic stellate cells
Loss of specialised tissue features
What type of epithelium is present in Barrets Oesophagus?
Specialised columnar epithelium - contains goblet cells and villi architecture or mimics gastric glands and contains mucus neck cells
Is metaplasia reversible?
POtentially yes, if the damaging stimuli is reversed before the damage progresses to dysplasia
Give three pathological examples of metaplasia.
Smoking - bronchi change from cilliated simple columnar to stratified sqaoumous cells, more resistant to chemical damage from cigarrete smoke but less mucocillary clearance.
Chronic endometriosis - uteurs lining changes from simple columnar to startified sqaoumous bettwe suited to chronic inflammation
