1. Quiz Discuss the importance of MHC in organ transplantation
What is the role of co-stimulatory signals (B7-1&2)
What are the principles of patient selection of organ recipient

2. Ischemia and Infarction
Dr. Karzan Mohammad
PhD. MSc. BSc.
Medical Biologist
Faculty of Education
Ishik University
100M Road
Erbil-Iraq
Tel.:
Research Fellow
Manchester Fungal Infection Group
The University of Manchester
Institute of Inflammation and Repair
Manchester, UK
M13 9NT
Tel
GBD Expert
Global Burden of Disease IHME Institute for Health Metrics and Evaluation
University of Washington
Seattle, WA 98121, USA

3. In the US: ~50% of deaths are due to ischemic heart disease (including myocardial infarction) ~15% of deaths are due to ischemic brain damage (including stroke)

4. Greek ischein“to restrain” + haima“blood”
Ischemia occurs when the blood supply to a tissue is inadequate to meet the tissue’s metabolic demands
Ischemia has 3 principal biochemical components: –Hypoxia (including anoxia) –Insufficiency of metabolic substrates –Accumulation of metabolic waste
Therefore, ischemia is a greater insult to the cells and tissues than hypoxia alone

5. Causes of Ischemia: Decreased Supply
•Vascular insufficiency: –Atherosclerosis –Thrombosis –Embolism –Compression
•Hypotension: –Shock –Hemorrhage

7. Causes of Ischemia: Increased Demand
•Increased tissue mass (hypertrophy)
•Increased workload (tachycardia, exercise)
•Increased tissue “stress” (cardiac dilatation)

8. Effect of Ischemia Depends on
Severity and Duration of Injury

9. Effect of Ischemia Depends on Cell Type
•“Parenchymal” cells are more susceptible than “stromal” cells
•Different parenchymal cells have different thresholds for ischemia: –
Neurons: 3-4 min
–Cardiac muscle, hepatocytes, renal tubular cells, gastrointestinal epithelium: min
–Fibroblasts, epidermis, skeletal muscle: hour

10. Detachment of Ribosomes
Loss of energy (ATP depletion, O2depletion)
Ischemia
Cellular responsesa
Na Pump
Influx of Ca++
Cellular Swelling
Mitochondria
Glycolysis
Glycogen pH
Clumping of Chromatin
Other effects
Detachment of Ribosomes
Protein Synthesis

11. Infarction
Latin infarctus, pp. of infarcire “to stuff” •An infarct is an area of tissue/organ necrosis caused by ischemia •Infarctions often result from sudden reduction of arterial (or occasionally venous) flow by thrombosis or embolism •Infarctions can also result from progressive atherosclerosis, spasms, torsions, or extrinsic compression of the vessels

13. Thrombus VS Embolus

14. Heart Attach Coronary artery Plaque Damage of tunice intima
Soft interior (fat, cholesterol, WBCs, Proteins, Calcium) thrombogenic
Hard Shell (Fibrous cap)

15. Timing 1 min. = Ischemia= Reversible
20 Minutes= Infarction= Irreversible

16. Symptoms of Infarction
Chest Pain
Nausea
Fatique
Dyspnia

18. Angina Stable Angina Non -Stable Angina 70% stenosis (plaque)
Endocardium been ischemic
Symptoms usually associated with exercise or stress and relief with rest
Non -Stable Angina
85-95% stenosis (Plaque + Thrombosis)
Ischemia
Even in rest times, the symptoms still in there.

19. Angina pectoris Hypoxia  Adenosine and Bradykinin  nervous response
 pressure, squeezing of chest  arms, shoulders involved  shortness of breath.

20. Arteriosclerosis
When endothelium of blood vessels becomes (Thicker, Harder. Less flexible)
Endothelium (Tunica intima)
Protection
Secretion of anticoagulants

21. Factors causing damage
Endothelium damage can be due to:
LDL
Smoking (Chemicals)
High blood pressure

22. Deposition of calcium
Inflammation
Increase of c-reactive protein
Can be anywhere in the body
Myocardial infarction

23. Thank you