NEET MDS Lessons
Physiology
Production of Hormones
The kidneys produce and interact with several hormones that are involved in the control of systems outside of the urinary system.
Calcitriol. Calcitriol is the active form of vitamin D in the human body. It is produced by the kidneys from precursor molecules produced by UV radiation striking the skin. Calcitriol works together with parathyroid hormone (PTH) to raise the level of calcium ions in the bloodstream. When the level of calcium ions in the blood drops below a threshold level, the parathyroid glands release PTH, which in turn stimulates the kidneys to release calcitriol. Calcitriol promotes the small intestine to absorb calcium from food and deposit it into the bloodstream. It also stimulates the osteoclasts of the skeletal system to break down bone matrix to release calcium ions into the blood.
Erythropoietin. Erythropoietin, also known as EPO, is a hormone that is produced by the kidneys to stimulate the production of red blood cells. The kidneys monitor the condition of the blood that passes through their capillaries, including the oxygen-carrying capacity of the blood. When the blood becomes hypoxic, meaning that it is carrying deficient levels of oxygen, cells lining the capillaries begin producing EPO and release it into the bloodstream. EPO travels through the blood to the red bone marrow, where it stimulates hematopoietic cells to increase their rate of red blood cell production. Red blood cells contain hemoglobin, which greatly increases the blood’s oxygen-carrying capacity and effectively ends the hypoxic conditions.
Renin. Renin is not a hormone itself, but an enzyme that the kidneys produce to start the renin-angiotensin system (RAS). The RAS increases blood volume and blood pressure in response to low blood pressure, blood loss, or dehydration. Renin is released into the blood where it catalyzes angiotensinogen from the liver into angiotensin I. Angiotensin I is further catalyzed by another enzyme into Angiotensin II.
Angiotensin II stimulates several processes, including stimulating the adrenal cortex to produce the hormone aldosterone. Aldosterone then changes the function of the kidneys to increase the reabsorption of water and sodium ions into the blood, increasing blood volume and raising blood pressure. Negative feedback from increased blood pressure finally turns off the RAS to maintain healthy blood pressure levels.
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+)
Hyperventilation
- Treatments :Rebreath air, hold breath (Increase CO2)
Give oxygen for Hypoxemia
The Types of muscle cells. There are three types, red, white, and intermediate.
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White Fibers Fast twitch Large diameter, used for speed and strength. Depends on the phosphagen system and on glycolysis-lactic acid. Stores glycogen for conversion to glucose. Fewer blood vessels. Little or no myoglobin. |
Red Fibers Slow twitch Small diameter, used for endurance. Depends on aerobic metabolism. Utilize fats as well as glucose. Little glycogen storage. Many blood vessels and much myoglobin give this muscle its reddish appearance. |
Intermediate Fibers: sometimes called "fast twitch red", these fibers have faster action but rely more on aerobic metabolism and have more endurance. Most muscles are mixtures of the different types. Muscle fiber types and their relative abundance cannot be varied by training, although there is some evidence that prior to maturation of the muscular system the emphasis on certain activities can influence their development
Factors , affecting glomerular filtration rate :
Factors that may influence the different pressure forces , or the filtration coefficient will affect the glomerular filtration rate .
1. Dehydration : Causes decrease hydrostatic pressure , and thus decreases GFR
2- Liver diseases that may decrease the plasma proteins and decrease the oncotic pressure , and thus increases glomerular filtration rate .
3- Sympathetic stimulation : will decrease the diameter of afferent arteriole and thus decreases glomerular filtration rate.
4- Renal diseases : Nephrotic syndrome for example decreases the number of working nephrons and thus decreases the filtration coefficient and thus decreases the glomerular filtration rate.
Glomerulonephritis will causes thickening of the glomerular basement membrane and thus decreases the glomerular filtration rate by decreasing the filtration coefficient too.
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 - 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