Blood tings pt1

explain gas exchange as a function of blood

carry oxygen and carbon dioxide in dissolved form

explain a function of blood in terms of solute distribution

plasma transports:

Ions,

nutrients,

hormones,

metabolic waste

explain the immune functions as a function of blood

leukocytes and immune system proteins are carried in the blood

how does blood maintain body temp? (as a function of blood)

blood carries away heat as a result of chemical reactions in the body

how does blood regulate clotting as a function of blood

platelets and certain proteins form clots to seal damaged blood vessels and prevent loss

how is acid base homeostasis maintained as a function of blood

pH of blood maintain at 7.4 average as a buffer

how is pressure maintained as a function of blood

blood volume is a major factor in determining blood pressure

list the constituents of the blood

erythrocytes, leukocytes and thrombocytes

list the proportions of blood parts in a sample

55% plasma of soluble materials and clot factors, 1% buffy coat of WBCs and platelets, 44% RBCs and haemocrit

define and list the normal hematocrit

percentage of total blood volume occupied by RBCs

42% in females, 45% in males

list the 2 main functions of plasma

thermoregulation, transport of material and dissolved gases

give the 3 plasma components and percentages

water 90%, plasma proteins 8%, dissolved, dissolved small molecules 1-2%

describe water in plasma

high heat holding capacity, blood temperature has small changes, unneeded heat lost to surroundings, water percentage determines viscosity

describe the components of plasma proteins and percentages

serum albumin 55%, globulins 38%, clotting proteins like fibrinogen 7%, 1% regulatory proteins

describe serum albumin

maintains osmotic pressure, assist in lipid and steroid hormone transport, large protein made in the liver

describe globulins

binds and transport ions, hormones and lipids otherwise incompatible with water based plasma, immune proteins made by leukocytes like antibodies or gammaglobulins

describe clotting proteins

essential for clotting and synthesised in liver

what is in the remainder of plasma

regulatory proteins like enzymes, proenzymes and hormones

what can be seen on electrophoresis of plasma proteins

albumin, alpha 1 and 2, beta and gamma peaks, diagnose myeloma by B and D bands

which nutrients are in the dissolved small molecules of plasma

glucose, amino acids, lipids and vitamins

which waste products are in the dissolved small molecules of plasma

creatinine, bilirubin, urea

which dissolved gases are in the small dissolved gases of plasma

oxygen and carbon dioxide

which 3 other substances are in the small dissolved molecules of plasma

hormones, vitamins and minerals

how are small dissolved molecules of plasma transported

in solution, readily exchanged between blood and ISF

describe the structure of RBCs

biconcave, more efficient for transport of oxygen

what is the MCV of red blood cells

80-96 femolitres

where are microcytic RBCs found

iron deficiency anaemia

where are macrocytic RBCs found

folate (vitamin B9) deficiency anaemia

where does red blood cell synthesis start

red bone marrow

explain RBC synthesis

hematopoietic stem cell - erythrocyte cfu - proerythroblast - early to late erythroblast - reticulocyte - erythrocyte

what can reticulocytes do

enter the bloodstream, which can be dangerous

explain the feedback loop

takes 26 days after a bleed, nucleus and organelles ejected in later stages, therefore no protein synthesis

explain the erythrocyte end of life steps

rupture, haemoglobin decomposed to haem and globin by phagocytosis, then leaves as bile pigments to faeces, urine or recycled to new RBCs

how can haem be decomposed

minus iron: biliverdin to bilirubin to bile, or Fe+ transferrin and stored in liver by ferritin

explain haemoglobins function

enables oxygen transport, oxygen is poorly soluble, 98% bounds to haemoglobin

what comprises haemoglobin

globin (4x quaternary chains), 4x Fe ions containing haem, so 1 molecules binds 4x oxygen

describe the haem group

has porphyrin ring, contains iron which appears red

give the charges of bound and and unbound irons

2+ is not bound, 3+ bound

which globin forms exist

alpha, beta, gamma, delta

give the haemoglobin types

HbA is 2 alpha and beta, HbA2 is 2 alpha and delta, HbF is 2 alpha and gamma, HbH is 4 beta in alpha thalassemia

how are alpha and beta globin coded for

alpha on 2 genes on chromosome 16, beta on 1 gene on chromosome 11

explain the binding of oxygen to haemoglobin

governed by ppO2 and number of available binding sites

explain the cooperative binding

as 1 binds, more are encouraged to bind by conformational change

what are the Hb forms

r- high O2 affinity, high pO2, firmly binds

t- low O2 affinity, low pO2, releases oxygen

what other substances can haemoglobin bind to

carbon dioxide, acidic hydrogen ion in carbonic acid, carbon monoxide, NO

what are the types of haemoglobin disorders

haemoglobinopathies: abnormal globin chains are made

thalassaemias: normal globins are made but in decreased amounts or are absent due to gene expression defects

describe sickle cell anaemia

genetic disease in beta globin mutation, E to G, so haemoglobin HbS polymerises at low pO2 forms long HbS crystals

what happens to sickled RBCs

become trapped within and block small blood vessels, depriving downstream tissues of oxygen

describe thalassemias

making of one or both of alpha or beta globins is reduced, causes by gross deletion of a gene mutation

describe alpha thalassemia

production of alpha reduced, excess beta chains, unstable tetramers of 4 beta chains, HbH, binds tightly reducing oxygen carrying capacity, damaged RBCs

describe beta thalassemia

results in iron overload and organ damage, excess alpha chains, no tetramers, bind and damage RBC membranes, high conc forms toxic aggregates

what is the clinical treatment for beta thalassemia

iron chelation therapy otherwise patients can accummilate fatal iron levels

what is caused by fragile RBCs that are short lived

anaemia

define haemostasis

arrest of bleeding from a broken blood vessel

which vessels are the haemostatic mechanisms in place for

preventing blood loss from small vessels like capillaries, venules and veins

describe platelets

formed elements, no nucleus, have budded off from large cells in bone marrow- megakaryocytes

what is platelet production regulated by

thrombopoietin- hormone produced in the liver and kidneys

describe platelet synthesis

hematopoietic stem cell, megakaryoblast, megakaryocytes where DNA is lost,, form arms which push into the blood vessel, break off as platelets

what do platelets contain

granules, microtubules, mitochondrion, plasma membrane

how are platelets stored, released and regulated

stored in spleen, released by contraction, regulated by autonomic nervous system

what is the life cycle of platelets

7-10 days, then apoptosis

what is the function of the exterior coat

rich in glycoproteins, adhesion, aggregation and activation

what is the function of the tubular system

site of thromboxane A2 synthesis and release

what is the function of microtubules and microfilaments

maintain shape

what is the function of alpha granules

contain clotting factors including von Willebrand factor, factors 5,7,8 and fibrinogen

what is the function of delta granules/ dense bodies

contain ADP, Ca2+ and serotonin, required for platelet activation and clotting

what are the 3 steps of hemostasis

vascular spasm, formation of platelet plug and blood coagulation

describe vascular spasm

cut/tear in vessel, damaged cells release vasoconstrictors giving smooth muscle contraction, slows blood flow

end of inner surfaces pushed together, become sticky and adhere to each other

how is vascular spasm aided by platelets

they stick to exposed collagen

what are the 3 steps in the platelet plug

compaction and strengthening/ further vasoconstriction, stimulation of the clotting cascade

describe prostacyclin, PG12

released by normal blood vessel lining, inhibits platelet aggregation, limits platelet plug to damaged region of vessel, stopping spread to normal tissue

explain the platelet plug

exposed collagen binds and activated platelets, platelet factors released, more platelets attracted, aggregation into plug

what happens in clotting

blood goes from liquid to a gel, fibrinogen converted to fibrin, RBCs enmeshed in the fibrin plug.

describe the clotting cascade

involved factor, thrombin F2a converts converts fibrinogen to fibrin monomers and F13a and Ca2+ F6 make polymer

what is the intrinsic pathway

initial stimulus is exposed collagen through endothelial wall damage

what is the extrinsic pathway

initial stimulus is blood contact with damaged tissue outside the vessel which exposes tissue factor (F3)

what is the common pathway

combination of intrinsic and extrinsic pathways in later coagulation stages

what are the initiation and amplification phases

tissue exposure initially triggers extrinsic pathway leading to thrombin production, but not enough (I), so thrombin produced feeds back and activated intrinsic pathway (A)

describe anti-thrombin as an anti-clotting system

inhibits clotting factors, activity enhanced by heparin, normally present in endothelial cells

describe tissue factor pathway inhibitor as an anti-clotting system

binds to the F3:7a complex to prevent it from activating its substrates (F9 and 10), binds F10a directly

describe thrombomodulin as an anti-clotting system

expressed by endothelial cells, binds thrombin, eliminates its coagulant effects and inactivates F5a and 8a

explain thrombin as an anti-clotting system

binds to receptor, simulated production of PGI, NO and ADP to inhibit further platelet aggregation

explain fibrinolysis

aggregated platelets secrete PDGF beta that recruits fibroblasts from the surrounding tissue, clot dissolved by plasmin

what forms scar tissue

fibroblasts

describe tissue plasminogen activator t-PA

activates fibrinolysis, secreted by endothelial cells, t-PA needs to bind fibrin to be active, hence only works on clot

which factors are which molecules

all except 3,5,7 and 13 are proteases

3,5 and 7 are glycoproteins

13 is a transglutaminase

what are the acquired or inherited disorder characteristics of haemostasis

excessive/unwanted/ inadequate clotting, qualitative or quantitative defects of platelets, coagulation factor deficiency/dysfunction

give some acquired disorders of haemostasis

renal disease, hepatic disease, vitamin k deficiency, drug-induced disorders

explain inherited disorders of haemostasis

structural defects to vascular system, thrombotic disorder, thrombocytopenia or thrombopathy, coagulation defects

define thrombus

blood clot in a vessel or the heart

define embolus

detached mass able to travel in vessel

define embolism

lodging of an embolus

define thromboembolism

blockage by a thrombus

define stenosis

abnormal narrowing of passage, only blocked at about 80%

what is in Virchow's triad of thrombosis risk factors

blood stasis, changes in vessel wall, thrombogenic changes in blood

describe thrombocytopenia

low platelet count, autoimmune, drug induced, easy bruising, rash, mucous membrane bleeding oro excessive bleeding after minor trauma