Inner compartment + blood + Immunphysiology Flashcards
what are the major 3 subcompartments of the EC space ?
- intravascular
- interstitial
- transcellular
what is the concentration for plasma water within the intravascular compartment ?
45 ml/bwkg
what is the concentration of blood cells within the intravascular compartment ?
35 ml/bwkg
what is the concentration of soft tissues within the interstitium compartment ?
120-150 ml/bwkg
what is the concentration of fibrous connective tissues within the interstitium compartment ?
45 ml/bwkg
what is the concentration of transcellular compartment ?
15ml/bwkg
how do you quantify volume ?
by steward dilution principle
How can we assess density by TBW?
weigh the mass (m)
quantify volume (V)
calculate density (m/V)
LBM has a constant water content of
73 %
fat has a constant water content of
10 %
what the TOBEC measures ?
the fat content of the body with high precision.
what fast distribution of the EC space using Stewart-principle can show us ?
volume of the soft tissues
what the slow distribution of the EC space using Stewart-principle can show us ?
volume of the soft and fibrous tissues
what the late distribution of the EC space using Stewart-principle can show us ?
volume of the bone tissue.
what forces move water ?
osmotic and hydrostatic
How long does it take to equalize the osmolality of the EC and IC compratments ?
few minutes
What are the symptoms of isoosmotic hypovolemia ?
hemorrage, burn, vomiting, diarrhoea
What are the symptoms of hyperosmotic hypovolemia ?
hydropenia:
decreased intake,
increased loss
increased evaporation
diabetes insipidus
What are the symptoms of hypoosmotic hypovolemia ?
decreasing salt intake
primary salt loss
intensive sweating
salt loss through the kidneys
hypoadrenocorticalismus
What are the symptoms of isoosmotic hypervolemia ?
oedema
overdosed physiological saline (per os or parenterally)
What are the symptoms of hyperosmotic hypervolemia ?
hyperosmotic fliod intake (per os or parenterally)
What are the symptoms of hypoosmotic hypervolemia ?
exaggerated water uptake.
Water retention in the kidney (ADH overproduction)
How long does it take to form isoosmosis between IC and EC ?
half an hour
How long does it take to restore isovolemia between IC and EC ?
couple of days
in P = r x C x R x T , what does the r mean ?
reflection coefficient
when membrane completely reflects a particle and it cannot get inside at all, what will be the value of reflection coefficient ?
1
what is the osmotic pressure for anelecctrolites of 1 mol dissolved substence in 1 liter ?
2.27 kPa
what is the unit which is used for measuring the body fluids ?
mmol/l
what is the unit which is used for measuring the osmotic pressure ?
kPa
what is the fpd of blood plasma?
- 0.56° C
what is the osmolality of fpd ?
300 mosmol/kg
What is oncotic pressure?
The pressure exerted specifically by protein and colloid in a compartment.
give 3 examples of anelectrolites components of the blood plasma and their concentrations
- Glucose -
mammals: 5 mmol/l
Ru: 3 mmol/l
Birds: 10 mmol/l - Urea - 3-10 mmol/l
- NPN (non-protein nitrogen) - 15-25 mmol/l
How can we quantify plasma proteins ?
with kjeldahl method
what is the concentration of amino acid in the plasma ?
5 mmol/l
what is the concentration of createnin in the plasma ?
50-200 μmol/l
what 2 independent proteins can be separated by paper-electrophoresis ?
albumin and fibrinogen
what size of molecules can get separated by ultracentrifuging ?
macromolecules
how does Ion exchange chromatography work ?
separates proteins on the basis of their charge
how protein mixture gets separated in Gel-filtration ?
by means of polysaccharide beads (dextran).
The protein with small molecular weight can get into the granules.
how does affinity chromatography work ?
one covalently binds a specific antibody formerly produced against the protein to the granules of the solid phase.
This protein will be selected from mixture by “recognizing system”, while the other proteins are washed away in short time.
how does immune electrophoresis work ?
Antibody distributed in a gel poured on a sheet of glass develops precipitation arcs with the antigen in the electric field.
how does HPLC work ?
divides proteins in a solide phase column under high pressure perfusion.
what is the concentration of albumin in the blood plasma ?
45 g/l
what is the concentration of alpha-1 globulin in the blood plasma ?
4 g/l
what is the concentration of alpha-2 globulin in the blood plasma ?
6 g/l
what is the concentration of beta globulin in the blood plasma ?
8 g/l
what is the concentration of fibrinogen in the blood plasma ?
3-6 g/l
what is the concentration of gamma globulin in the blood plasma ?
15 g/l
what are the main functions of plasma proteins ?
- Maintaining the oncoting pressure.
- Transport funtions of albumins, globulins and lipoproteins.
- Blood sedimentation.
- Buffer action.
- Blood clotting.
- Immunity - immunoglobulins, complement proteins and signal proteins and peptides.
- Enzymes in the plasma.
- General protein metabolism - 25% plasmapheresis.
which protein in the plasma is responsible for most of the maintanace of oncotic pressure ?
albumin
what materials can albumin bind to and transport ?
- fatty acids
- bilirubin
- hormones
- vitamins
- metal ions (calcium, weakly: copper and zinc)
what materials can globulin bind to and transport ?
- transferrin: iron
- haptoglobin: hem
- transcortin: corticoids
- TBG (thyroxin binding globulin): thyroxin
- transcobalamin: B12-vitamin
- lipoproteins: see later
- wide variety of transport proteins
what VLDL stands for ?
Very Low Density Lipoprotein
what IDL stands for ?
Intermediate Density Lipoprotein
what LDL stands for ?
Low Density Lipoprotein
what HDL stands for ?
High Density Lipoprotein
what happens if erythrocyte sedimentation rate is high ?
there is more chance that inflammation present in the body.
Originally the cells have great negative charge because of the
albumin, so they repulse each other very much and sediment slowly. BUT After the globulins bind the total charge will decrease, there will be less repulse among the red blood cells so the sedimentation will get faster.
Plasma proteins are responsible for __% of buffer capacity of the blood.
7
Plasma proteins are responsible for __% of buffer capacity of the plasma.
15
hemoglobin is responsible for __% of buffer capacity of the blood.
35
All coagulation factors are plasma proteins execpt ________
calcium ion (coagulation factor IV)
plasma proteins are the precursors of
anticoagulation and fibrinolysis
Immunoglobulins are part of ________ immunity
specific
Complement proteins are part of _________ immunity
non-speacific
10 g/l decrease means ___ kg decrease on the total protein content of the body
1
All the proteins synthesized in the liver, except :
- gamma globulins: plasma cells.
- HDL and VLDL: intestinal epithelium.
- ic enzymes: from heart, liver, etc.
in which organ most of the proteins are synthesized ?
liver
what will hypo-and hyperproteinemia cause to the body ?
starving, kidney disease
what will dysproteinemia cause to the body ?
ratio changes,
e.g. :albumin/globulin
what will paraproteinemia cause to the body ?
pathological proteins appear, e.g. tumor Bence-Jones proteins
Define proteinemia
a lack of some of the fractions
(genetic, e.g. fibrinogen)
What two important factors determine the formation of the ISF ?
transport through the capillary wall and forces determining transport
what can pass through the capillary wall without restriction ?
Water, electrolites and anelectrolites with small molecular weight.
which material movement is restricted in the capillary wall ?
Protein.
(only a small amount of it can get through to the ISF mainly by pynocytosis and exocytosis)
If the protein transport into ISF is slow, why the protein concentration of the ISF is still high ?
while great part of the fluid moving out of the
capillary gets back to the capillary, so called Gibbs-Donnan effect, the proteins cannot get back.
what is the name of the capillary in the liver which is permeable for proteins ?
sinusoid
What is the only component which cannot pass the capillary wall BUT only by the help of specific carrier systems ?
colloids
What are fenestrated capillaries?
have pores that span the endothelial cells and allow larger molecules to pass
name different ways of transport through the membrane, from Intravascular space to the Intrerstitial space
- Through fenestration.
- Through interendothelial ways.
- In atrancellular way.
- By endocytosis, exocytosis, pynocytosis.
What determines the composition of the ISF ?
Diffusion, osmotic conditions, electric forces and hydrostatic forces.
What is the most important force to ensure transport of substances by which the most substances cross the capillary membrane without restriction ?
diffusion
what will happen if the movement of some component is restricted between two compartments
the concentration of the diffusible ions will be different in the two compartments.
what will happen if both, the freely diffusible electrolytes (KCl) and the non-diffusible proteinate anions are present in container which has dyalizing membrane ?
proteinate anions attract cations, thus the distribution of the diffusible ions will be unequal on the two sides of the membrane.
(after the balance developed)
what is electroneutrality ?
the total amount of anions and cations have to be equal in certain compartments.
what are the forces that control the capillary/ISF balance ?
- Osmotic pressure -continuously moves water into the plasma.
- Hydrostatic pressure continuously move water out of the plasma.
on the arterial end of the capillary hydrostatic pressure os higher than the oncotic one, what is the result ?
filtration
On the venous end of the capillary oncotic pressure is higher than the hydrostatic one, what is the result ?
resorption
what is the most well known kind of ISF overproduction (isoosmotic hypervolemia)
odema
in the capillary/ISF boarder the ________ end difference is higher than the ________ end.
arterial, venous
what are the main causes of edema ?
- Increased hydrostatic pressure = increased filtration.
- decreased plasma proteins within the capillaries = decreased reabsorption.
- increased capillary permeability.
- Blockage of lymphatic drainage.
- Increased blood pressure.
why protein is considered as the cells’ “main problem” in the intracellular fluid ?
cells needs the protein.
Proteins do not have a considerable osmotic effect, but they have got charge and therefore they attract a lot of ions from the EC compartment and in this way
osmolarity inside the cells increases very much.
If the cell does not protect itself from the high pressure, such a high amount of water may flow into the cell that it ruptures the cell.
how the protozoa cell protects itself from the high pressure water flow inside the cell ?
water pump
how the plant cell protects itself from the high pressure water flow inside the cell ?
thick cell wall
how the mammalian cell protects itself from the high pressure water flow inside the cell ?
ion pump
what is blood primary function ?
transportation
what have the red blood cells specialized for ?
transportation of gases
what have the white blood cells specialized for ?
defense
where is the bivalent iron located at the red blood cell ?
hem-base
what is the main duty of the neutrophil granulocytes ?
phagocytosis, as part of the natural defense
what is the main duty of the basophil granulocytes ?
bind the IgE antibodies with their receptors and in case they meet the adequate antigen (pathogenic agent), they empty proteolytic enzymes in the interstitium (degranulation). This loosens the tissues, immune cells can get into the interstitium.
what is the main duty of the eosinophil granulocytes ?
act against the over-reaction of the basophils and partly are responsive to parazitosis.
what is the main duty of the thrombocytes ?
play a role in the defense reaction and in hemostasis.
what is the main duty of the B-lymphocytes ?
main cells of the humoral immunity.
what is the main duty of the T-lymphocytes ?
main cells of the cellular immunity.
What are the transport functions examples of the blood ?
- transport of blood gases
- transport of nutrients
- transport of metabolits
- information transport
- heat-transport
what is the total buffer capacity (%) of bicarbonate buffers in the blood ?
53
what is the total buffer capacity (%) of non-bicarbonate buffers in the blood ?
47
define haemostasis
coagulation, the body’s normal physiological response for the prevention and stopping of bleeding/haemorrhage
what are the conditions of homeostasis ?
- isovolemia (constant volume)
- isotonia (constant osmotic pressure)
- isoionia (constant ion-composition)
- isohydria (constant pH)
what is the water proportion in blood (%) ?
90
what are the corpuscular elements in the blood ?
red blood cells, white blood cells, thrombocytes.
what is serum ?
plasma fluid after the blood cells and the clotting proteins have been removed - no fibrinogen present, only fibrin.
what is plasma ?
liquid portion of blood; contains fibrinogen, water, proteins, salts, nutrients, lipids, hormones, and vitamins.
define hematocrit
the ratio of the volume of corpuscular elements to the total volume of blood.
(hematocrit shows us the velocity of the sedimentation of corpuscular elements)
Hematocrit avarage values (%)
40
dog Venous Ht-values
0.46
hen Venous Ht-value
0.32
What is sedimentation?
process of allowing particles in suspension in water to settle out of the suspension under the effect of gravity.
Blood cell sedimentation of horse
60-70 mm/hour
Blood cell sedimentation of dog
5-10 mm/hour
Blood cell sedimentation of swine
1-14 mm/hour
Blood cell sedimentation of hen
1-4 mm/hour
Blood cell sedimentation of cattle
0-2 mm/hour
Blood cell sedimentation of human
3-10 mm/hour
Blood pH range
7.35-7.45 (slightly alkaline)
what is the flexible range of blood pH for a short time period ?
pH 7.1 (minimum) - pH 7.6 (maximum)
the pH of the venous vessels is _______ than the pH of the arterial vessels.
lower
denisty of plasma
1020 g/l
total density of blood
1050 g/l
denisty of blood cells
1090 g/l
total osmotic pressure
700 kPa
colloidosmotic (oncotic) pressure
2.7-4 kPa
osmolality
300 mmol/kg
blood volume
80 ml/bwt
plasma volume
45 ml/ttkg
blood cell volume
35 ml/ttkg
what substances help to determine the plasme space ?
- Evans blue
- 125-I or131-I.
-labeled: albumin,
globulin, fibrinogen.
what substances help to determine the blood cell volume?
- labeled red blood cells
(32-P, 55-or 59-Cr, 51-Fe)
1,4,7 - ?
Normocythaemia :
- Normocythaemic normovolaemia.
- Normocythaemic hypovolaemia (Oligaemia) - blood loss, blood cells and plasma loss together.
- Normocythaemic hypervolaemia - plethora, excess transfusion, permanent, exhausting physical work.
2,5,8 - ?
Polycythaemia:
- Polycythaemic normovoloaemia - haemoconcentration, viscosity increases, increased load on heart (turbulence).
- Polycythaemic hyopvoloaemia - anhydraemia: lack of water, thirst, end up with haemoconcentration.
- Polycythaemic hypervolaemia.
3,6,9 - ?
Olygocythaemia:
- Olygocythaemic normovoloaemia - haemodilution, blood gets diluted with concurrent normal volume.
- Olygocythaemic hypovoloaemia.
- Olygocythaemic hypervolaemia - hydraemia, intake of excess water, infusion(followed by haemodilution).
what are the factors that affect the blood volume ?
- amount of body fat.
- position of the body.
- muscle work.
- climate.
- nutrition.
- lack of oxygen.
- sympathetic activity.
- pregnancy.
- blood loss.
- changes in the total water supply.
the blood volume of new born
100 ml/bwt
the blood volume of an adult
80 ml/bwt
Red blood cells have no _________
mitochondria
red blood cells can make energy only by __________
anaerobic respiration
what is the avarage lifetime of a red blood cell ?
120 days
what is the lifetime of cattle, swine red blood cell ?
60 days
what is the lifetime of bird red blood cell ?
30 days
what is the hemoglobin amount in the blood ?
120-180 g/l
how many grams Hb for 1g RBC ?
0.35 g Hb
?
MCHC (Hb/Ht)
Mean Corpuscular Hemoglobin Concentration.
- Approximately: 5 mmol/l.
?
MCH (Hb/RBC)
Mean Corpuscular Hemoglobin.
- Approximately: 0.45 pc/l.
?
MCV (Ht/RBC)
Mean Corpuscular Volume
- Approximately: 80-100 pc/l.
what is Hemolysis?
leakage or disruption of the blood cells (mainly red blood cells).
how can RBC adapt to change easily ?
Their special membrane characteristics, which has spectrin-protein-molecules on the internal side that provides flexible feature.
These “molecular springs” are fixed forming a net on the internal side of the cell by ankyrine, actin and smaller connective molecules.
Red blood cells are resistant to the quite significant changes of the osmotic circumstances = osmotic resistance.
(Slight changes in the osmolality do not cause
permanent damage, only changing of the shape)
what slightly hyperosmotic environment will cause the red blood cell ?
change in shape - smaller size
(osmotic resistance)
what slightly hypoosmotic environment will cause the red blood cell ?
change in shape - larger size.
(osmotic resistance)
what is the minimal concentration for osmotic resistance ?
70-120 mmol/l NaCl.
(Haemolysis just starts)
what is the maximal concentration for osmotic resistance ?
50-90 mmol/l NaCl
(All the cells haemolyse)
how haemolysis of RBC can be caused ?
primary injury of the RBCs membrane
?
Spectrin
?
ankyrine
?
actin-bridge
What is hemoglobin?
the pigment (protein) coloring the red blood cells that plays main role in the transport of the blood gases and the forming of the blood’s buffer capacity
How many sub units does hemoglobin have?
4
What is hemoglobin level in the blood ?
120-180 g/l blood
what is hem ?
non-protein part of the hemoglobin.
Consist of ferro-protoporphyrine.
In the porphyrine base iron has only four co-ordination sites.
The two other valences involved are bound to the imidazole ring of the protein (histidine) under and over the porphyrine base.
Only the bivalent iron (ferro) atom can bind the oxygen reversibly.
what is globin ?
protein part of hemoglobin, which its sterical structure of globin mainly determines the characteristics of the oxygen binding.
Allows allosteric stimulation, and it is able to bind a new oxygen even stronger after accepting the former one.
only the bivalent ____ atom can bind the oxygen reversibly
iron (ferro) Fe2+
What causes sickle cell anemia?
single amino acid change in the beta chain of hemoglobin - in the 6th position there is glutamine instead of alanine
why Hb-F has smaller affinity to the 2,3-DPG than the Hb-A ?
Amino acid sequence difference.
What are the chains of an adult animal Hb-A ?
2 alpha + 2 beta chain
What are the chains of a foetal periodl Hb-F ?
2 alpha + 2 gamma chain
hoy many oxygen molecules can 1 hem bind to ?
1
What is carbaminohemoglobin?
hemoglobin bound to carbon dioxide, which is responsible for about 20 % of the compete CO2 blood-transport.
Hemoglobin has affinty to
- carbon monoxide reversibly (with about 200 times bigger affinity than to oxygen),
- OH and Cl radicals.
- Can go through methaemoglobin (hemiglobin) forming during nitrate or nitrite intoxication.
what are the 2 most important buffer-bases in the blood ?
The Hb- anion and HCO3-
what is the acid/base pair that ensures the buffer action in hemoglobin ?
HHb/Hb-
35% of the buffer capacity of the blood is provided by ___________
hemoglobin
What is the RBC lifespan in the blood circulation?
120 days
what happens to normal RBC, after 120 days in the circulation ?
become sphaerocytes
which organs filter the sphaerocytes?
spleen and liver
1,2,3,4,5 ?
1. Normal RBC-s age after 120 days in the
circulation - they become
sphaerocytes.
2. The spleen and the liver filter the sphaerocytes:
1% of the RBC-supply undergoes hemolysis daily.
3. released:
- hemoglobin
- RBC debris
4. The hemoglobin partly gets into the blood: haptoglobin binds it.
In case haptoglobin is saturated: hemoglobinaemia followed by hemoglobinuria.
The free plasma hem binds to hemopexin.
5. Large part of the hemoglobin is degraded inside the phagocytes.
when phagocyte eats hemoglobin, that transforms the globin and HEM to ___________
globin → amino acid.
HEM → Fe2+ and protoporfirin-IX which furthermore changes to bilirubin.
During the degradation of the hemoglobin phagocytes convert the HEM part to __________
bilirubin
Bilirubin 1 consists of
albumin and Bilirubin which bind in the circulation
1,2,3,4,5,6,7,8,9,10,11,12,13,14 ?
1. Br-I
(+80% glucoronic acid,
+20% sulphate)
2. Br-II “direct billirubin”
3. Bile
4. Br-II enters interstitial lumen (then changes)
5. Br-I
6. UBG - urobilinogen (15%)
7. stercobilinogen (gets oxidized)
8. stercobilin - as feaces (85%)
9. other products - as feaces
10. vena portae by vv. hemorrhoidales
11. hepatocyte (becomes after to Br-I again)
12. systemic circulation (1%)
13. kidney
14. UBG - as urin
Describe the degradation of the hemoglobin
Bilirubin dissociates from the albumin and it is taken up by the hepatocytes. A major proportion of bilirubin is conjugated with glucuronic acid, while the rest with other molecules. This is called the conjugated bilirubin, or direct bilirubin, or bilirubin-II
- Bilirubin is excreted to the bile and ends up in the gut where it is first deconjugated by bacteria, then further degradation products produced. The most important degradation products are stercobilinogen, stercobilin(which makes the feces brown), and urobilinogen (UBG). Most of the UBG is absorbed in the gut entering the portal circulation and finally ending up in the liver. The UBG is converted back to bilirubin. A small part of UBG is absorbed by the vv hemorriodhales, entering the systemic circulation and excreted by the kidney.
- The whole degradation process has clinical relevance. The origin of the icterus can be diagnosed measuring degradation products.