NEET MDS Lessons
Physiology
1.Rhythmicity ( Chronotropism ) : means the ability of heart to beat regularly ( due to repetitive and stable depolarization and repolarization ) . Rhythmicity of heart is a myogenic in origin , because cardiac muscles are automatically excited muscles and does not depend on the nervous stimulus to initiate excitation and then contraction . The role of nerves is limited to the regulation of the heart rate and not to initiate the beat.
There are many evidences that approve the myogenic and not neurogenic origin of the rhythmicity of cardiac muscle . For example :
- transplanted heart continues to beat regularly without any nerve supply.
- Embryologically the heart starts to beat before reaching any nerves to them.
- Some drugs that paralyze the nerves ( such as cocaine ) do not stop the heart in given doses.
Spontaneous rhythmicity of the cardiac muscle due to the existence of excitatory - conductive system , which is composed of self- exciting non-contractile cardiac muscle cells . The SA node of the mentioned system excites in a rate , that is the most rapid among the other components of the system ( 110 beats /minute ) , which makes it the controller or ( the pacemaker ) of the cardiac rhythm of the entire heart.
Mechanism , responsible for self- excitation in the SA node and the excitatory conductive system is due to the following properties of the cell membrane of theses cells :
1- Non-gated sodium channels
2- Decreased permeability to potassium
3- existence of slow and fast calcium channels.
These properties enable the cations ( sodium through the none-gated sodium voltage channels , calcium through calcium slow channels) to enter the cell and depolarize the cell membrane without need for external stimulus.
The resting membrane potential of non-contractile cardiac cell is -55 - -60 millivolts ( less than that of excitable nerve cells (-70) ) .
The threshold is also less negative than that of nerve cells ( -40 millivolts ).
The decreased permeability to potassium from its side decrease the eflux of potassium during the repolarization phase of the pacemaker potential . All of these factors give the pacemaker potential its characteristic shape
Repeating of the pacemaker potential between the action potentials of contractile muscle cells is the cause of spontaneous rhythmicity of cardiac muscle cells.
Factors , affecting the rhythmicity of the cardiac muscle :
I. Factors that increase the rate ( positive chronotropic factors) :
1. sympathetic stimulation : as its neurotransmitter norepinephrine increases the membrane permeability to sodium and calcium.
2. moderate warming : moderate warming increases temperature by 10 beats for each 1 Fahrenheit degree increase in body temperature, this due to decrease in permeability to potassium ions in pacemaker membrane by moderate increase in temperature.
3. Catecholaminic drugs have positive chronotropic effect.
4. Thyroid hormones : have positive chronotropic effect , due to the fact that these drugs increase the sensitivity of adrenergic receptors to adrenaline and noreadrenaline .
5. mild hypoxia.
6. mild alkalemia : mild alkalemia decreases the negativity of the resting potential.
7. hypocalcemia.
8. mild hypokalemia
II. Factors that decrease rhythmicity ( negative chronotropic):
1.Vagal stimulation : the basal level of vagal stimulation inhibits the sinus rhythm and decrease it from 110-75 beats/ minute. This effect due to increasing the permeability of the cardiac muscle cell to potassium , which causes rapid potassium eflux , which increases the negativity inside the cardiac cells (hyperpolarization ).
2. moderate cooling
3. severe warming : due to cardiac damage , as a result of intercellular protein denaturation. Excessive cooling on the other hand decrease metabolism and stops rhythmicity.
4. Cholenergic drugs ( such as methacholine , pilocarpine..etc) have negative chronotropic effect.
5. Digitalis : these drugs causes hyperpolarization . This effect is similar to that of vagal stimulation.
6. Hypercapnia ( excessive CO2 production )
7. Acidemia.
8. hyper- and hyponatremia .
9. hyperkalemia
10. hypercalcemia
11. Typhoid or diphteria toxins.
CNS PROTECTION
- Bones of the Skull Frontal, Temporal, Parietal, Sphenoid, Occipital
- Cranial Meninges Dura mater, Arachnoid Space, Pia mater
- Cerebrospinal Fluid
Secreted by Chroid Plexi in Ventricles
Circulation through ventricles and central canal
Lateral and Median apertures from the 4th ventricle into the subarachnoid space
Arachnoid villi of the superior sagittal sinus return CSF to the venous circulation
Hydrocephalic Condition, blockage of the mesencephalic aqueduct, backup of CSF, Insertion of a shunt to drain the excess CSF
HEART DISORDERS
- Pump failure => Alters pressure (flow) =>alters oxygen carrying capacity.
- Renin release (Juxtaglomerular cells) Kidney
- Converts Angiotensinogen => Angiotensin I
- In lungs Angiotensin I Converted => Angiotensin II
- Angiotensin II = powerful vasoconstrictor (raises pressure, increases afterload)
- stimulates thirst
- stimulates adrenal cortex to release Aldosterone
(Sodium retention, potassium loss) - stimulates kidney directly to reabsorb Sodium
- releases ADH from Posterior Pituitary
- Myocardial Infarction
- Myocardial Cells die from lack of Oxygen
- Adjacent vessels (collateral) dilate to compensate
- Intracellular Enzymes leak from dying cells (Necrosis)
- Creatine Kinase CK (Creatine Phosphokinase) 3 forms
- One isoenzyme = exclusively Heart (MB)
- CK-MB blood levels found 2-5 hrs, peak in 24 hrs
- Lactic Dehydrogenase found 6-10 hours after. points less clearly to infarction
- Serum glutamic oxaloacetic transaminase (SGOT)
- Found 6 hrs after infarction, peaks 24-48 hrs at 2 to 15 times normal,
- SGOT returns to normal after 3-4 days
- Creatine Kinase CK (Creatine Phosphokinase) 3 forms
- Myocardium weakens = Decreased CO & SV (severe - death)
- Infarct heal by fibrous repair
- Hypertrophy of undamaged myocardial cells
- Increased contractility to restore normal CO
- Improved by exercise program
- Prognosis
- 10% uncomplicated recovery
- 20% Suddenly fatal
- Rest MI not fatal immediately, 15% will die from related causes
- Congenital heart disease (Affect oxygenation of blood)
- Septal defects
- Ductus arteriosus
- Valvular heart disease
- Stenosis = cusps, fibrotic & thickened, Sometimes fused, can not open
- Regurgitation = cusps, retracted, Do not close, blood moves backwards
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
Remember the following principles before proceeding :
- Reabsorption occurs for most of substances that have been previously filterd .
- The direction of reabsorption is from the tubules to the peritubular capillaries
- All of transport mechanism are used here.
- Different morphology of the cells of different parts of the tubules contribute to reabsorption of different substances .
- There are two routes of reabsorption: Paracellular and transcellular : Paracellular reabsorption depends on the tightness of the tight junction which varies from regeon to region in the nephrons .Transcellular depends on presence of transporters ( carriers and channels for example).
1. Reabsorption of glucose , amino acids , and proteins :
Transport of glucose occurs in the proximal tubule . Cells of proximal tubules are similar to those of the intestinal mucosa as the apical membrane has brush border form to increase the surface area for reabsorption , the cells have plenty of mitochondria which inform us that high amount of energy is required for active transport , and the basolateral membrane of the cells contain sodium -potassium pumps , while the apical membrane contains a lot of carrier and channels .
The tight junction between the tubular cells of the proximal tubules are not that (tight) which allow paracellular transport.
Reabsorption of glucose starts by active transport of Na by the pumps on the basolateral membrane . This will create Na gradient which will cause Na to pass the apical membrane down its concentration gradient . Glucose also passes the membrane up its concentration gradient using sodium -glucose symporter as a secondary active transport.
The concentration of glucose will be increased in the cell and this will enable the glucose to pass down concentration gradient to the interstitium by glucose uniporter . Glucose will then pass to the peritubular capillaries by simple bulk flow.
Remember: Glucose reabsorption occurs via transcellular route .
Glucose transport has transport maximum . In normal situation there is no glucose in the urine , but in uncontrolled diabetes mellitus patients glucose level exceeds its transport maximum (390 mg/dl) and thus will appear in urine .
2. Reabsorption of Amino acids : Use secondary active transport mechanism like glucose.
3. Reabsorption of proteins :
Plasma proteins are not filtered in Bowman capsule but some proteins and peptides in blood may pass the filtration membrane and then reabsorbed . Some peptides are reabsorbed paracellulary , while the others bind to the apical membrane and then enter the cells by endocytosis , where they will degraded by peptidase enzymes to amino acids .
4. Reabsorption of sodium , water , and chloride:
65 % of sodium is reabsorbed in the proximal tubules , while 25% are reabsorbed in the thick ascending limb of loob of Henle , 9% in the distal and collecting tubules and collecting ducts .
90% of sodium reabsorption occurs independently from its plasma level (unregulated) , This is true for sodium reabsorbed in proximal tubule and loop of Henle , while the 9% that is reabsorbed in distal ,collecting tubules and collecting ducts is regulated by Aldosterone.
In proximal tubules : 65% of sodium is reabsorbed . The initial step occurs by creating sodium gradient by sodium-potassium pump on the basolateral membrane . then the sodium will pass from the lumen into the cells down concentration gradient by sodium -glucose symporter , sodium -phosphate symporter and by sodium- hydrogen antiporter and others
After reabsorption of sodium , an electrical gradient will be created , then chloride is reabsorbed following the sodium . Thus the major cation and anion leave the lumen to the the interstitium and thus the water follows by osmosis . 65% of water is reabsorbed in the proximal tubule.
Discending limb of loop of Henle is impermeable to electrolytes but avidly permeable to water . 10 % of water is reabsorbed in the discending thin limb of loob of Henle .
The thick ascending limb of loop of Henly is permeable to electrolytes , due to the presence of Na2ClK syporter . 25% of sodium is reabsorbed here .
In the distal and collecting tubules and the collecting ducts 9% of sodium is reabsorbed .this occurs under aldosterone control depending on sodium plasma level. 1% of sodium is excreted .
Water is not reabsorbed from distal tubule but 5-25% of water is reabsorbed in collecting tubules .
1) Storage - the stomach allows a meal to be consumed and the materials released incrementally into the duodenum for digestion. It may take up to four hours for food from a complete meal to clear the stomach.
2) Chemical digestion - pepsin begins the process of protein digestion cleaving large polypeptides into shorter chains .
3) Mechanical digestion - the churning action of the muscularis causes liquefaction and mixing of the contents to produce acid chyme.
4) Some absorption - water, electrolytes, monosaccharides, and fat soluble molecules including alcohol are all absorbed in the stomach to some degree.
Micturition (urination) is a process, by which the final urine is eliminated out of the body .
After being drained into the ureters, urine is stored in urinary bladder until being eliminated.
Bladder is a hollow muscular organ, which has three layers:
- epithelium : Composed of superficial layer of flat cells and deep layer of cuboidal cells.
- muscular layer : contain smooth muscle fibers, that are arranged in longitudinal, spiral and circular pattern . Detrusor muscle is the main muscle of bladder. The thickening of detrusor muscle forms internal urinary sphinctor which is not an actual urinary sphincter. The actual one is the external urinary sphincter, which is composed of striated muscle and is a part of urogenital diaphragm.
- adventitia: composed of connective tissue fibers.
So: There are two phases of bladder function that depend on characterestics of its muscular wall and innervation :
1. Bladder filling : Urine is poured into bladder through the orifices of ureters. Bladder has five peristaltic contraction per minute . These contraction facilitate moving of urine from the ureter to the bladder as prevent reflux of urine into the ureter.. The capacity of bladder is about 400 ml. But when the bladder start filling its wall extends and thus the pressure is not increased with the increased urine volume.
2. Bladder emptying : When bladder is full stretch receptors in bladder wall are excited , and send signals via the sensory branches of pelvic nerves to the sacral plexus. The first urge to void is felt at a bladder volume of about 150 ml. In sacral portion of spinal cord the sensory signals are integrated and then a motor signal is sent to the urinarry blader muscles through the efferent branches of pelvic nerve itself.
In adult people the neurons in sacral portion could be influenced by nerve signals coming from brain ( Micturition center in pons ) that are also influenced by signals coming from cerebral cortex.
So: The sensory signals ,transmitted to the sacral region will also stimulate ascending pathway and the signals be also transmitted to the micturition center in the brain stem and then to the cerebrum to cause conscious desire for urination.
If micturition is not convenient the brain sends signals to inhibit the parasympathetic motor neuron to the bladder via the sacral neurons.
It also send inhibitory signal via the somatomotor pudendal nerve to keep external urinary sphincter contracting.
When micturition is convenient a brain signal via the sacral neurons stimulate the parasympathetic pelvic nerve to cause contraction of detruser muscle via M-cholinergic receptors and causes relaxation of external urinary sphincter and the micturition occurs.
Sympathetic hypogastric nerve does not contribute that much to the micturition reflex. It plays role in prvrntion reflux of semen into urinary bladder during ejaculation by contracting bladder muscles.