NEET MDS Lessons
Physiology
Normal Chemical Composition of Urine
Urine is an aqueous solution of greater than 95% water, with a minimum of these remaining constituents, in order of decreasing concentration:
Urea 9.3 g/L.
Chloride 1.87 g/L.
Sodium 1.17 g/L.
Potassium 0.750 g/L.
Creatinine 0.670 g/L .
Other dissolved ions, inorganic and organic compounds (proteins, hormones, metabolites).
Urine is sterile until it reaches the urethra, where epithelial cells lining the urethra are colonized by facultatively anaerobic gram-negative rods and cocci. Urea is essentially a processed form of ammonia that is non-toxic to mammals, unlike ammonia, which can be highly toxic. It is processed from ammonia and carbon dioxide in the liver.
Contractility : Means ability of cardiac muscle to convert electrical energy of action potential into mechanical energy ( work).
The excitation- contraction coupling of cardiac muscle is similar to that of skeletal muscle , except the lack of motor nerve stimulation.
Cardiac muscle is a self-excited muscle , but the principles of contraction are the same . There are many rules that control the contractility of the cardiac muscles, which are:
1. All or none rule: due to the syncytial nature of the cardiac muscle.There are atrial syncytium and ventricular syncytium . This rule makes the heart an efficient pump.
2. Staircase phenomenon : means gradual increase in muscle contraction following rapidly repeated stimulation..
3. Starling`s law of the heart: The greater the initial length of cardiac muscle fiber , the greater the force of contraction. The initial length is determined by the degree of diastolic filling .The pericardium prevents overstretching of heart , and allows optimal increase in diastolic volume.
Thankful to this law , the heart is able to pump any amount of blood that it receives. But overstretching of cardiac muscle fibers may cause heart failure.
Factors affecting contractility ( inotropism)
I. Positive inotropic factors:
1. sympathetic stimulation: by increasing the permeability of sarcolemma to calcium.
2. moderate increase in temperature . This due to increase metabolism to increase ATP , decrease viscosity of myocardial structures, and increasing calcium influx.
3. Catecholamines , thyroid hormone, and glucagon hormones.
4. mild alkalosis
5. digitalis
6. Xanthines ( caffeine and theophylline )
II. Negative inotropic factors:
1. Parasympathetic stimulation : ( limited to atrial contraction)
2. Acidosis
3. Severe alkalosis
4. excessive warming and cooling .
5. Drugs ;like : Quinidine , Procainamide , and barbiturates .
6. Diphtheria and typhoid toxins.
Heart sounds
Heart sounds are a result of beating heart and resultant blood flow . that could be detected by a stethoscope during auscultation . Auscultation is a part of physical examination that doctors have to practice them perfectly.
Before discussion the origin and nature of the heart sounds we have to distinguish between the heart sounds and hurt murmurs. Heart murmurs are pathological noises that results from abnormal blood flow in the heart or blood vessels.
Physiologically , blood flow has a laminar pattern , which means that blood flows in form of layers , where the central layer is the most rapid . Laminar blood flow could be turned into turbulent one .
Turbulent blood flow is a result of stenotic ( narrowed ) valves or blood vessels , insufficient valves , roughened vessels` wall or endocardium , and many diseases . The turbulent blood flow causes noisy murmurs inside or outside the heart.
Heart sounds ( especially first and second sounds ) are mainly a result of closure of the valves of the heart . While the third sound is a result of vibration of ventricular wall and the leaflets of the opened AV valves after rapid inflow of blood from the atria to ventricles .
Third heart sound is physiologic in children but pathological in adults.
The four heart sound is a result of the atrial systole and vibration of the AV valves , due to blood rush during atrial systole . It is inaudible neither in adults nor in children . It is just detectable by the phonocardiogram .
Characteristic of heart sounds :
1. First heart sound (S1 , lub ) : a soft and low pitch sound, caused by closure of AV valves.Usually has two components ( M1( mitral ) and T1 ( tricuspid ). Normally M1 preceads T1.
2. Second heart sound ( S2 , dub) : sharp and high pitch sound . caused by closure of semilunar valves. It also has two components A2 ( aortic) and P2 ( pulmonary) . A2 preceads P2.
3. Third heart sound (S3) : low pitched sound.
4. Fourth heart sound ( S4) very low pitched sound.
As we notice : the first three sounds are related to ventricular activity , while the fourth heart sound is related to atrial activity.
Closure of valves is not the direct cause for heart sounds , but sharp blocking of blood of backward returning of blood by the closing valve is the direct cause.
Blood Groups
Blood groups are created by molecules present on the surface of red blood cells (and often on other cells as well).
The ABO Blood Groups
The ABO blood groups are the most important in assuring safe blood transfusions.
Blood Group |
Antigens on RBCs |
Antibodies in Serum |
Genotypes |
A |
A |
Anti-B |
AA or AO |
B |
B |
Anti-A |
BB or BO |
AB |
A and B |
Neither |
AB |
O |
Neither |
Anti-A and anti-B |
OO |
When red blood cells carrying one or both antigens are exposed to the corresponding antibodies, they agglutinate; that is, clump together. People usually have antibodies against those red cell antigens that they lack.
The critical principle to be followed is that transfused blood must not contain red cells that the recipient's antibodies can clump. Although theoretically it is possible to transfuse group O blood into any recipient, the antibodies in the donated plasma can damage the recipient's red cells. Thus all transfusions should be done with exactly-matched blood.
The Rh System
Rh antigens are transmembrane proteins with loops exposed at the surface of red blood cells. They appear to be used for the transport of carbon dioxide and/or ammonia across the plasma membrane. They are named for the rhesus monkey in which they were first discovered.
There are a number of Rh antigens. Red cells that are "Rh positive" express the one designated D. About 15% of the population have no RhD antigens and thus are "Rh negative".
The major importance of the Rh system for human health is to avoid the danger of RhD incompatibility between mother and fetus.
During birth, there is often a leakage of the baby's red blood cells into the mother's circulation. If the baby is Rh positive (having inherited the trait from its father) and the mother Rh-negative, these red cells will cause her to develop antibodies against the RhD antigen. The antibodies, usually of the IgG class, do not cause any problems for that child, but can cross the placenta and attack the red cells of a subsequent Rh+ fetus. This destroys the red cells producing anemia and jaundice. The disease, called erythroblastosis fetalis or hemolytic disease of the newborn, may be so severe as to kill the fetus or even the newborn infant. It is an example of an antibody-mediated cytotoxicity disorder.
Although certain other red cell antigens (in addition to Rh) sometimes cause problems for a fetus, an ABO incompatibility does not. Rh incompatibility so dangerous when ABO incompatibility is not
It turns out that most anti-A or anti-B antibodies are of the IgM class and these do not cross the placenta. In fact, an Rh−/type O mother carrying an Rh+/type A, B, or AB fetus is resistant to sensitization to the Rh antigen. Presumably her anti-A and anti-B antibodies destroy any fetal cells that enter her blood before they can elicit anti-Rh antibodies in her.
This phenomenon has led to an extremely effective preventive measure to avoid Rh sensitization. Shortly after each birth of an Rh+ baby, the mother is given an injection of anti-Rh antibodies. The preparation is called Rh immune globulin (RhIG) or Rhogam. These passively acquired antibodies destroy any fetal cells that got into her circulation before they can elicit an active immune response in her.
Rh immune globulin came into common use in the United States in 1968, and within a decade the incidence of Rh hemolytic disease became very low.
An anti-diruetic is a substance that decreases urine volume, and ADH is the primary example of it within the body. ADH is a hormone secreted from the posterior pituitary gland in response to increased plasma osmolarity (i.e., increased ion concentration in the blood), which is generally due to an increased concentration of ions relative to the volume of plasma, or decreased plasma volume.
The increased plasma osmolarity is sensed by osmoreceptors in the hypothalamus, which will stimulate the posterior pituitary gland to release ADH. ADH will then act on the nephrons of the kidneys to cause a decrease in plasma osmolarity and an increase in urine osmolarity.
ADH increases the permeability to water of the distal convoluted tubule and collecting duct, which are normally impermeable to water. This effect causes increased water reabsorption and retention and decreases the volume of urine produced relative to its ion content.
After ADH acts on the nephron to decrease plasma osmolarity (and leads to increased blood volume) and increase urine osmolarity, the osmoreceptors in the hypothalamus will inactivate, and ADH secretion will end. Due to this response, ADH secretion is considered to be a form of negative feedback.
1 - Passive processes - require no expenditure of energy by a cell:
- Simple diffusion = net movement of a substance from an area of high concentration to an area of low concentration. The rate of diffusion is influenced by:
- concentration gradient
- cross-sectional area through which diffusion occurs
- temperature
- molecular weight of a substance
- distance through which diffusion occurs
- Osmosis = diffusion of water across a semi permeable membrane (like a cell membrane) from an area of low solute concentration to an area of high solute concentration
- Facilitated diffusion = movement of a substance across a cell membrane from an area of high concentration to an area of low concentration. This process requires the use of 'carriers' (membrane proteins). In the example below, a ligand molecule (e.g., acetylcholine) binds to the membrane protein. This causes a conformational change or, in other words, an 'opening' in the protein through which a substance (e.g., sodium ions) can pass.
2 - Active processes - require the expenditure of energy by cells:
- Active transport = movement of a substance across a cell membrane from an area of low concentration to an area of high concentration using a carrier molecule
- Endo- & exocytosis - moving material into (endo-) or out of (exo-) cell in bulk form
Transport of Carbon Dioxide
A. Dissolved in Blood Plasma (7-10%)
B. Bound to Hemoglobin (20-30%)
1. carbaminohemoglobin - Carb Dioxide binds to an amino acid on the polypeptide chains
2. Haldane Effect - the less oxygenated blood is, the more Carb Diox it can carry
a. tissues - as Oxygen is unloaded, affinity for Carb Dioxide increases
b. lungs - as Oxygen is loaded, affinity for Carb Dioxide decreases, allowing it to be released
C. Bicarbonate Ion Form in Plasma (60-70%)
1. Carbon Dioxide combines with water to form Bicarbonate
CO2 + H2O <==> H2CO3 <==> H+ + HCO3-
2. carbonic anhydrase - enzyme in RBCs that catalyzes this reaction in both directions
a. tissues - catalyzes formation of Bicarbonate
b. lungs - catalyzes formation of Carb Dioxide
3. Bohr Effect - formation of Bicarbonate (through Carbonic Acid) leads to LOWER pH (H+ increase), and more unloading of Oxygen to tissues
a. since hemoglobin "buffers" to H+, the actual pH of blood does not change much
4. Chloride Shift - chloride ions move in opposite direction of the entering/leaving Bicarbonate, to prevent osmotic problems with RBCs
D. Carbon Dioxide Effects on Blood pH
1. carbonic acid-bicarbonate buffer system
low pH → HCO3- binds to H+
high pH → H2CO3 releases H+
2. low shallow breaths → HIGH Carb Dioxide → LOW pH (higher H+)
3. rapid deep breaths → LOW Carb Dioxide → HIGH pH (lower H+)