NEET MDS Lessons
Physiology
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 .
The large intestine (colon)
The large intestine receives the liquid residue after digestion and absorption are complete. This residue consists mostly of water as well as materials (e.g. cellulose) that were not digested. It nourishes a large population of bacteria (the contents of the small intestine are normally sterile). Most of these bacteria (of which one common species is E. coli) are harmless. And some are actually helpful, for example, by synthesizing vitamin K. Bacteria flourish to such an extent that as much as 50% of the dry weight of the feces may consist of bacterial cells. Reabsorption of water is the chief function of the large intestine. The large amounts of water secreted into the stomach and small intestine by the various digestive glands must be reclaimed to avoid dehydration.
Cardiac Output:
Minute Volume = Heart Rate X Stroke Volume
Heart rate, HR at rest = 65 to 85 bpm
Each heartbeat at rest takes about .8 sec. of which .4 sec. is quiescent period.
Stroke volume, SV at rest = 60 to 70 ml.
Heart can increase both rate and volume with exercise. Rate increase is limited due to necessity of minimum ventricular diastolic period for filling. Upper limit is usually put at about 220 bpm. Maximum heart rate calculations are usually below 200. Target heart rates for anaerobic threshold are about 85 to 95% of maximum.
Terms:
End Diastolic Volume, EDV - the maximum volume of the ventricles achieved at the end of ventricular diastole. This is the amount of blood the heart has available to pump. If this volume increases the cardiac output increases in a healthy heart.
End Systolic Volume, ESV - the minimum volume remaining in the ventricle after its systole. If this volume increases it means less blood has been pumped and the cardiac output is less.
EDV - ESV = SV
SV / EDV = Ejection Fraction The ejection fraction is normally around 50% at rest and will increase during strenuous exercise in a healthy heart. Well trained athletes may have ejection fractions approaching 70% in the most strenuous exercise.
Isovolumetric Contraction Phase - a brief period at the beginning of ventricular systole when all valves are closed and ventricular volume remains constant. Pressure has risen enough in the ventricle to close the AV valves but not enough to open the semilunar valves and cause ejection of blood.
Isovolumetric Relaxation Phase - a brief period at the beginning of ventricular diastole when all valves are closed and ventricular volume is constant. Pressure in the ventricle has lowered producing closure of the semilunar valves but not opening the AV valves to begin pulling blood into the ventricle.
Dicrotic Notch - the small increase in pressure of the aorta or other artery seen when recording a pulse wave. This occurs as blood is briefly pulled back toward the ventricle at the beginning of diastole thus closing the semilunar valves.
Preload - This is the pressure at the end of ventricular diastole, at the beginning of ventricular systole. It is proportional to the End Diastolic Volume (EDV), i.e. as the EDV increases so does the preload of the heart. Factors which increase the preload are: increased total blood volume, increased venous tone and venous return, increased atrial contraction, and the skeletal muscular pump.
Afterload - This is the impedence against which the left ventricle must eject blood, and it is roughly proportional to the End Systolic Volume (ESV). When the peripheral resistance increases so does the ESV and the afterload of the heart.
The importance of these parameters are as a measure of efficiency of the heart, which increases as the difference between preload and afterload increases
Bile - produced in the liver and stored in the gallbladder, released in response to CCK . Bile salts (salts of cholic acid) act to emulsify fats, i.e. to split them so that they can mix with water and be acted on by lipase.
Pancreatic juice: Lipase - splits fats into glycerol and fatty acids. Trypsin, and chymotrypsin - protease enzymes which break polypeptides into dipeptides. Carboxypeptidase - splits dipeptide into amino acids. Bicarbonate - neutralizes acid. Amylase - splits polysaccharides into shorter chains and disaccharides.
Intestinal enzymes (brush border enzymes): Aminopeptidase and carboxypeptidase - split dipeptides into amino acids. Sucrase, lactase, maltase - break disaccharides into monosaccharides. Enterokinase - activates trypsinogen to produce trypsin. Trypsin then activates the precursors of chymotrypsin and carboxypeptidase. Other carbohydrases: dextrinase and glucoamylase. These are of minor importance.
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
A heart rate that is persistently greater than 100bpm is termed tachycardia. A heart rate that is persistantly lower than 60 pulse per min is termed bradycardia. Let's examine some factors that could cause a change in heart rate:
- Increased heart rate can be caused by:
- Increased output of the cardioacceleratory center. In other words, greater activity of sympathetic nerves running to the heart and a greater release of norepinephrine on the heart.
- Decreased output of the cardioinhibitory center. In other words, less vagus nerve activity and a decrease in the release of acetylcholine on the heart.
- Increased release of the hormone epinephrine by the adrenal glands.
- Nicotine.
- Caffeine.
- Hyperthyroidism - i.e., an overactive thyroid gland. This would lead to an increased amount of the hormone thyroxine in the blood.
- Decreased heart rate can be caused by:
- Decreased activity of the cardioacceleratory center.
- Increased activity of the cardioinhibitory center.
- Many others.
Platelets
Platelets are cell fragments produced from megakaryocytes.
Blood normally contains 150,000 to 350,000 per microliter (µl). If this value should drop much below 50,000/µl, there is a danger of uncontrolled bleeding. This is because of the essential role that platelets have in blood clotting.
When blood vessels are damaged, fibrils of collagen are exposed.
- von Willebrand factor links the collagen to platelets forming a plug of platelets there.
- The bound platelets release ADP and thromboxane A2 which recruit and activate still more platelets circulating in the blood.
- (This role of thromboxane accounts for the beneficial effect of low doses of aspirin a cyclooxygenase inhibitor in avoiding heart attacks.)
ReoPro is a monoclonal antibody directed against platelet receptors. It inhibits platelet aggregation and appears to reduce the risk that "reamed out" coronary arteries (after coronary angioplasty) will plug up again.