Clinical Biochemistry: An Overview and Key Concepts
1) Overview of clinical biochemistry L1
History of IR provide us various information to find some systemic explanation and to generalise knowledge about IR
●History of any discipline is important to self-understanding.
●To explain how IR is viewed by other disciplines
●This historic vision can provide us a special attention to specific events and processes
●History might be seen as an illustration of theoretical concepts.
1. extensive, vast question with your opinion.
From her lectures: 1) methods of explanation and means of justifying a position;2) problem of values and political position;
can be given as an example: Max Weber “Science as a Vocation” 1917 , where he proves the need to study theories, paradigms etc.(“no science is free of assumptions and the value of science is list when its assumptions are rejected”)
2) The Great debates (How many ‘great debates’ there are? Name all of the ‘great debates’);
3) The Great debates concept (Kuhn’s description of scientific revolutions and paradigms in IR according to B.Schmidt)
1. Blood Background L1
-Transportation: Gases, nutrients, wastes, hormones
-Regulation:Body fluid pH, body temperature, electrolyte balance
-Protection:Blood clotting, immune cells
-Have Plasma,Serum(clotted,no clotting factor), Proteins, Solute
Red blood cell: 99%in blood, 120 day life long, Hamemoglobin(carry O2), Biconcave disc
No nucleus or organelles
-Hb: Haem groups, Four protein subunits: α1, α2, β1, and β2.
-O2 Dissociation Curve: Left shfit=More oxygen keep in Hb, pH↑,DPG↓,Temp↓
Right shift= More oxygen relesae. pH↓,DPG↑,Temp↑
-Interleukin is used to signal stem cell become different cell
White blood Cell ( all of them have surface Protein ask markers)
-Granulocyte(具有小颗粒的白细胞) (basophils 0.5-1% +neutrophils 60 – 70% +eosinophils 2-4%)
-Agranulocyte (lymphocyte 20-25%→T,B,NK cell) +(monocyte 3-8%)
Platelets(Blood clotting by aggregation) 5-9 days
-From megakaryocyte(巨核细胞), Disc shapte,Disc-shaped(圆盘状) fragments with vesicle.
-From liver( Alumin) carriers, osmotic regulators, activated by 1 2 cations, haem, bilirubin.
-Immunoglobulin. From Immune system. Trigger protective immune responses
Haematology L2
Haematostatic reponse(止血):3 factors.
-Interaction of Blood vessel wall +Circulating platelets +Blood coagulation factors
Vasoconstriction(血管收缩): Contraction of smooth muscle to contract wall of artery for decrasing bleeding rate
-Mechanism: 受伤血管的即时血管收缩,邻近小动脉和小动脉的反射性收缩,最初流向受伤区域的血流变慢→contact activation of platelets and coagulation factors
-Platelet structure
Extremely small (3.0 x 0.5 umeter; 7-11 femtoLitres) 表面上的糖蛋白对粘附和聚集很重要.
含有参与血小板聚集的储存颗粒(granules).
Function: 响应血管损伤形成机械栓塞(mechanical plug)
Activation:ADP, TXA2
Blood coagulation cascade
-Two ways (Intrinsic and extrinsic)
Intrinsicr由与异物表面接触启动 : Occur in minutes. Damage tissue→XII→XI→IX→X
Extrinsic:由组织损伤启动 in seconds. Damage tissue→VIIa→proteolytic activities→IX +X→IXa +Xa→thrombin
Common: X→Prothrombin→fibrinogen→fibrin II→Fibrin I(纤维蛋白 )
Animea
O2 carrying capacity ↓ Causes: RBCs↓ Hb↓
Range: Man Hb: 13.5-17.5 Female Hb: 11.5-15.5
Symptoms:Shortness of breath (SOB), particularly on exertion,Weakness,Lethargy (昏睡),Palpitation
(心慌),Headache.
Response: Increase stroke volume and tachycardia (心動過速) Shift of Hb oxygen dissociation curve, Shift O2 curve to right. El
-Rapidly progressive anaemia causes more symptoms, Less time for adaptation responses
-Hb
Hypochromic anaemias: By ion deficiency MCV↓ MCH↓
平均红细胞体积（MCV）和平均红细胞血红蛋白（MCH）
Iron required for haem synthesis. Transport and storage largely mediated by transferrin, transferrin receptor (TfR) 1, and ferritin
-Transferrin(Contain up to 2 iron ions)将铁输送到表达 TfR 的组织（骨髓中的祖细胞),铁主要来源于红细胞的回收血红素, 可重复利用
Iron Balance
Control method: By intake and loss. Eat 20mg only 10% can be abosrbed
Loss:Sloughed cell脱落的细胞/失血
Factor:铁store的状态,红细胞生成,最近的铁摄入量
被reticuloendothelial 网状内皮 (RE) 系统中的巨噬细胞破坏 Cell become non viable
Break down process: Break down Haem→ release iron to plasma transferrin/ Porphyrin→bilirubin in liver/ globin→amino acid
Haemolytic anaemias
Increase in the rate of RBC destruction
Two type: 遗传, Acquired
Mechanisms: 血管外：巨噬细胞对 RE 系统的过度清除/血管内：循环中过度分解
遗传Hereditary: Membrane defects, herditary spherocytosis,膜骨架与脂质双分子层相互作用异常
Metabolism defects: glucose-6-phosphate dehydrogenase (G6PD) deficiency¯G6PD ð¯NADPH ð¯glutathione ð¯protection from oxidative stress
Acquired:Autoimmune haemolytic anaemias (AIHAs)
-Production of autoantibody against RBCs
-Drug-induced immune haemolytic anaemias/ Infections, eg. malaria
Macrocytic anaemias 红细胞异常大
Megaloblastic巨幼细胞性:缺乏维生素 B12 或叶酸/DNA 合成缺陷/红细胞细胞核成熟延迟/骨髓红细胞异常
酒精、肝病、细胞毒性药物cytotoxic、怀孕、吸烟等引起的非巨幼细胞性贫血
-B12 structure like heme, but the fe+ replace by cobalt CO+, form folic acid, Cofactor: N5 MTHF →THF
Folate: Form dTMP, dUMP → dTMP→ form DNA
Pernicious anaemia: lead B12↓ 由自身免疫攻击胃粘膜引起/↓intrinsic factor 的分泌（由胃壁细胞）
Non-megaloblastic:
血红蛋白遗传病: 地贫Thalasssaemias/ Sickle cell anaemia
骨髓/红细胞生成问题:再生障碍性贫血/先天性红细胞生成不良性贫血
Leukaemia白血病
未成熟造血细胞的肿瘤性增殖/骨髓和血液中恶性白细胞 (WBC) 的积累/引起骨髓衰竭和器官浸润
基于临床进展和细胞谱系的分类
Chronic myeloid leukaemia (CML)
Clonal disorder of pluripotent stem cell →CML BCR-ABL1+
Accounts for 15% of leukaemias. Diagnosis characterized by Philadelphia (Ph) chromosome
CML BCR-ABL1+: Ph 染色体：9 号和 22 号染色体之间的易位. 部分癌基因ABL1（9）移至BCR基因（22）→Ph染色体
ABL1-BCR 编码融合蛋白 → 组成型活性酪氨酸激酶
symptoms:Bone marrow failure/Bone pain and tenderness/Anaemia/Decrease in functional WBC number/Infection due to weakened immunity/Decrease in platelet number/Enlargement of internal organs
Haemophilia(血友病)
Affect blood clotting Mechanism : Genetic deficiency of blood clotting factors/Impaired blood clotting
Type A + B. TypeA: 最常见的遗传性凝血因子缺乏症/经典血友病/与大出血相关的遗传病/凝血因子 VIII 遗传缺陷 (8) (affected intrinstric way)
Chr X: 153.72 – 153.9 Mb