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

Ischemia and Infarction Dr. Karzan Mohammad PhD. MSc. BSc. Medical Biologist Faculty of Education Ishik University 100M Road Erbil-Iraq Tel.: 07504095454 Research Fellow Manchester Fungal Infection Group The University of Manchester Institute of Inflammation and Repair Manchester, UK M13 9NT Tel. 07927133678 GBD Expert Global Burden of Disease IHME Institute for Health Metrics and Evaluation University of Washington Seattle, WA 98121, USA

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)

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

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

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

Effect of Ischemia Depends on Severity and Duration of Injury

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: 20-80 min –Fibroblasts, epidermis, skeletal muscle: hour

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

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

Thrombus VS Embolus

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

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

Symptoms of Infarction Chest Pain Nausea Fatique Dyspnia

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.

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

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

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

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

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