Molecules and Blood 🩸

Explain the potency of cells

Potency refers to how much the cell can differentiate:

Totipotent - can differentiate into any cell type in the body

Pluripotent - can differentiate into any cell type except the placenta, they are found in the embryo

Multipotent - can differentiate into blood cells, they are found in the bone marrow also known as adult stem cells

Unipotent - can only differentiate into one cell type eg skin

What is Haematopoiesis

Haematopoiesis is the differentiation of a multipotent stem cell into myeloid projector cells or lymphoid projector cells they can then further differentiate into blood cells such as RBS, lymphocytes, neutrals, monocytes, platelets, NK cells.

What is a zymogen

An inactive substance which is responsible for activating proteins

where is erythropoietin produced

kidneys

where is thrombopoietin produced

liver

function of erythropoietin

signals to RBC precursors in bone marrow to increase RBC proliferation

function of thrombopoietin

signals to platelet precursors and megakaryocytes in bone marrow to increase megakaryocyte production which will result in platelet shedding

How is RBC regenerated?

Signals are sent to RBC projector cells (erythropoietins) in the bone marrow, this triggers proliferation of the RBC, resulting in increased RBC production.

What are some advantages and disadvantages of stem cells

Adult stem cells have a fewer ability of differentiation, and are more difficult to isolate and culture, although embryonic stem cells are better at this there is ethical concerns around this such as destruction of an embryo, when does it become life, some believe it becomes life at conception.

Discuss Stem cells in cancer

There can be two types of stem cells transplant, autologous and allogenic. Allogenic is when a donors stem cells are transplanted, used for treatments in leukemia, thalassaemia, sickle cell anaemia. Autologous is used for some cases of MS, lymphoma, myeloma.

What is the definition of shock

Shock is a form of acute circulatory failure with inadequate oxygen delivery and utilisation of cells and it can result in organ dysfunction or death.

What are the different types of shock

Distributive; vasoregulation fails, so blood vessels often go leaky and dilated. anaphylactic, sepsis, neurogenic. Anaphylaxis is a response to allergic reaction. Sepsis is a toxic effect of inflammatory response. Neurogenic is vagal tone problems caused by spinal cord damage.

Hypovalaemic; haemorrhage and non-haemorrhage. Haemorrhage is a loss of blood and non-haemorrhage is the loss of fluids.

Obstructive; obstruction to the flow of blood to and from the heart

Cardiogenic; the heart fails to pump effectively

What is the symptoms of type 1 shock

Mental; normal

BP; normal

Pulse; <100

Resp; 14-20

Urine; >30

Blood loss; <750

% of blood volume; up to 15

What are the symptoms of type 2 shock

Mental; mildly anxious

BP; normal

Pulse; >100

Resp; 20-30

Urine; 20-30

Blood loss; 750-1500

% of blood volume; 15-30

What are the symptoms of type 3 shock

Mental; anxious

BP; decreased

Pulse; >120

Resp; 30-40

Urine; 5-15

Blood loss; 1500-2000

% of blood volume; 30-40

What are the symptoms of type 4 shock

Mental; confused

BP; decreased

Pulse; >140

Resp; >40

Urine; negligible

Blood loss; >2000

% of blood volume; >40

What are the types of wound

Abrasion; first layer of skin removed

Laceration; uneven edges, often goes deep

Incised; slash or a stab, can appear small but often go very deep and can be very dangerous

Degloving; the skin and the blood supply both come away

Biting; very unhygienic, can be human or animal

How should trauma be managed

Airways - is anything blocking their airway

Breathing - is the patient managing to breathe properly or do they sound wheezy etc

Circulation - pressure and elevation

What is the central dogma

Central dogma is the flow of genetic information. DNA > RNA > proteins

Explain the process of transcription

Initiation; RNA polymerase II binds to promoter and DNA strands separate

Elongation; RNA strand grows

Termination; RNA polymerase II dissociates

Compare the genome, transcriptome and the proteome

Genome; the entire genetic material composition that an organism has

Proteome; all of the proteins produces by an organism

Transcriptome; all of the mRNA of an organism

How can multiple proteins be produced from the same gene

Due to alternative RNA splicing of pre-RNA-transcript. This creates different mature mRNA transcripts which then code for different proteins.

What is a TF

A transcription factor is a factor which binds to small specific regions of DNA and can turn on/off transcription.

What is the role of activators and represseors

This is due to activators and repressors. Activators promote the binding of RNA polymerase II to promoters and repressors inhibit the binding of RNA polymerase II.

How can TFs be turned on/off

Enhancers promote the TF and gene expressions and Silencers prevent the TF and gene expression.

What is meant by primary, secondary, tertiary & quaternary

Primary; the order of amino acids

Secondary; the first role of amino acids and can be alpha helix, beta pleated sheets.

Tertiary; the 3D structure of a polypeptide

Quaternary; when two or more polypeptides are joined together.

What are some post translational modifications

Phosphorylation; alter activity of protein

Ubiquitination; label protein for degradation

Acetylation; regulate gene transcription

Glycosylation; folding in the ER

And there is proteolytic cleavage where proteins can be turned from inactive to active eg prothrombin > thrombin

What is constitutive gene expression

Genes which are always expressed, in every cell, at same stages. They are the genes which maintain basic cell function

What is inductive gene expression

Genes which are not always expressed, only expressed in certain cells and only at certain times.

How do mutations alter protein function and result in disease

A mutation causes amino acid sequence to be altered, the protein will then be wrongfully coded for and can result in it having a different function or shape so can’t carry out the role that it was intended to do. Eg Cystic Fibrosis is a mutation to CFTR protein which normally regulates mucus transport in the lungs and pancreas.

Outline the process of fibrinolysis

This is the process of converting fibrin into fibrin degradation products. Plasminogen is converted to plasmin and this is catalysed by tPA and thrombin, this causes the breakdown of fibrin, however there is also the inactivation of factor XIII as this will prevent fibrin from re-cross-linking.

What is the process of the coagulation pathway

What effect does heparin have on coagulation

Heparin binds to and enhances the role of AT III, this inhibits both the intrinsic and common pathway

How does Warfarin effect the coagulation pathway

warfarin is a vitamin K antagonist so it blocks the liver from using vitamin K to create coagulation factors, meaning this can effect the whole pathway.

How does Benzamide effect the coagulation pathway

it competitively inhibits prothrombin and factor X, without these fibrinogen will not be converted to fibrin so a clot will not be formed

How does amino-caproic acid affect the coagulation cascade

Amino-caloric acid is an anti-fibrinolysis, meaning it inhibits the plasminogen to prevent the formation of plasmin, so clots cannot be broken down

What is the role of chelated calcium

Chelated calcium is an anti-coagulant, it is formed when sodium citrate/EDTA is added to calcium

What is an APTT assay

An APTT assay measures the length of time it takes for a clot to form from the initiation of the INTRINSIC pathway.

What is a PT assay

A PT assay measures the length of time it takes for a clot to form from the beginning of the EXTRINSIC pathway.

What does it mean if an APTT assay with a low value

This means that there is an increased chance of blood clotting which can be very dangerous, this could be due to an excess in any of the factors involved.

What does it mean if an APTT assay is too high

This means that a person is not forming clots fast enough and they may be experiencing excessive blood loss, this could be due to factor deficiency resulting in haemophilia, a presence of an inhibitor, VWD or vit K deficiency.

What happens if someone has a vitamin k deficiency or liver disease

If someone has a vit K deficiency then they may fail to create coagulation factors. If they have liver disease then this the liver may fail to signal to vit K to produce coagulation factors.

What can occur when APTT is too low

DVT; a blood clotting in the leg which has the ability to move elsewhere

PE; a blood clot in the lung which can prevent oxygen as it blocks a pulmonary artery

Stroke; a blood clot in the brain due to a lack of blood and oxygen to the brain, can cause brain damage if it goes without oxygen for so long or can cause death

Heart; blood clot in the heat can prevent blood from leaving/entering the heart, this can cause cardiac muscle to die ore cause a myocardial infarction.

What is the causes of haemophilia

Haemophilia A - factor VIII deficiency

Haemophilia B - factor IX deficiency

It is an X-linked genetic disorder

What is the effect of VWD

This is when there is a deficiency in VWF making it more difficult for platelets to bind or prevents them, making the formation of a platelet plug more difficult or preventing the formation.

What is the components of the blood

Red blood cells, white blood cells, platelets and plasma

What is the role of plasma

Plasma carries blood cells, nutrients, hormones, antibodies around the body. It also regulate temperature and pH and maintains blood pressure and volume.

What is the function of RBC

They are necessary in the transportation of oxygen from the lungs to tissues and also transport CO2 from tissues to lungs

What is the structure of RBC

They have a biconcave shape which maximises surface area for transportation of oxygen, when oxygen binds to RBC the haemoglobin in them becomes oxyhaemoglobin. Haemoglobin is composed of 4 haem groups and 4 polypeptides (2 alpha & 2 beta). RBC are produced by the bone marrow and the bone marrow is instructed to do this by erythropoietin which are produced in the kidney of adults. RBC are removed by the spleen. When the haemoglobin within RBC clumps together it creates sickle cell anaemia.

Describe the formation of the platelet plug

Firstly there is vasoconstriction of the blood vessels to prevent the loss of lots of blood. The sub-endothelial lining is exposed as well as the collagen, collagen creates a sticky base which Von Willebrand factor binds to, the platelets then bind to the VWF and signal other platelets to bind to the VWF. Platelet aggregation then occurs and they all clump together and form a temporary clot. This is primary haemostasis.

What is the function of platelets

To form blood clots

What is the function of monocytes

They clean up damaged cells

What is the function of Lymphocytes

There is two types; T & B. They protect against viral infections by producing antibodies.

What is the function of Neutrophils

They kill bacteria, fungi and foreign debris

What is the function of Basophils

They carry out an allergic response

What is the function of eosinophils

They kill cancer cells and parasites

What are some effects of mutations in TF

Mutation to binding site; thalassaemia, the amount of mRNA produced may be reduced

Mutation to TF; p53 mutation (found in 50% of cancer patients), distrusts the normal cell cycle

What results in basal levels of transcription

basal TF binding

What is a zymogen

A zymogen is an inactive substance which activates proteins.

What are the two factors involved in gene expression

TF and the structure of DNA

How does the structure of DNA effect gene expression

Euchromatin is open - gene can be expressed

Heterochrmatin is closed - gene cannot be expressed

This is due to proteins called histones which bind DNA, modifications to histones causes DNA to wrap/unwrap. Locus control regions can also cause chromatin to open.

Define coagulation

Formation of a blood clot, blood goes from liquid to solid

Define anticoagulant

compounds which prevent blood clotting

What is haemostasis

the stopping of bleeding

What is thrombosis and thrombus

Thrombosis is the formation of a dangerous blood clot

Thrombus is the blood clot

What is the role of proteolysis in clot formation

Proteolysis can convert inactive proteins to active proteins so can activated the coagulation cascade.

Where are the different types of stem cell found

Totipotent; zygote

Pluripotent; inner cell mass of zygote

Multipotent; bone marrow

What is the cause of factor V Leiden

Factor V is usually activated/inactivated by protein C, when an individual has factor v Leiden it resists the effect of protein C causing blood clotting to go on for longer, forming excessive blood clots.

What is the effect of prothrombin gene mutation

This is when there is a mutation to the Factor II gene, this causes the production of too much prothrombin.

What is the effect of protein S deficiency

Protein S is a natural anticoagulant, without it it may be difficult for the body to control the coagulation pathway.

What is the effect of excessive clotting factors

Too many clots will be made

What is albumin and globulin

These are components which make up the blood plasma, albumin has a function in maintaining fluidity and pressure whilst globulin is responsible for transportation of substances, nutrients, hormones

What factors do vitamin K effect

Factor 2, 7,9,10