NEET MDS Lessons
Physiology
DNA (Deoxyribonucleic acid) - controls cell function via transcription and translation (in other words, by controlling protein synthesis in a cell)
Transcription - DNA is used to produce mRNA
Translation - mRNA then moves from the nucleus into the cytoplasm & is used to produce a protein . requires mRNA, tRNA (transfer RNA), amino acids, & a ribosome
tRNA molecule
- sequence of amino acids in a protein is determined by sequence of codons (mRNA). Codons are 'read' by anticodons of tRNAs & tRNAs then 'deliver' their amino acid.
- Amino acids are linked together by peptide bonds (see diagram to the right)
- As mRNA slides through ribosome, codons are exposed in sequence & appropriate amino acids are delivered by tRNAs. The protein (or polypeptide) thus grows in length as more amino acids are delivered.
- The polypeptide chain then 'folds' in various ways to form a complex three-dimensional protein molecule that will serve either as a structural protein or an enzyme.
GENERAL SOMATIC AFFERENT (GSA) PATHWAYS FROM THE BODY
Pain and Temperature
Pain and temperature information from general somatic receptors is conducted over small-diameter (type A delta and type C) GSA fibers of the spinal nerves into the posterior horn of the spinal cord gray matter .
Fast and Slow Pain
Fast pain, often called sharp or pricking pain, is usually conducted to the CNS over type A delta fibers.
Slow pain, often called burning pain, is conducted to the CNS over smaller-diameter type C fibers.
Touch and Pressure
Touch can be subjectively described as discriminating or crude.
Discriminating (epicritic) touch implies an awareness of an object's shape, texture, three-dimensional qualities, and other fine points. Ability to recognize familiar objects simply by tactile manipulation.
The conscious awareness of body position and movement is called the kinesthetic sens
Crude (protopathic) touch, lacks the fine discrimination described above and doesn't generally give enough information to the brain to enable it to recognize a familiar object by touch alone.
Subconscious Proprioception
Most of the subconscious proprioceptive input is shunted to the cerebellum.
Posterior Funiculus Injury
Certain clinical signs are associated with injury to the dorsal columns.
As might be expected, these are generally caused by impairment to the kinesthetic sense and discriminating touch and pressure pathways.
They include
(1) the inability to recognize limb position,
(2) astereognosis,
(3) loss of two-point discrimination,
(4) loss of vibratory sense, and
(5) a positive Romberg sign.
Astereognosis is the inability to recognize familiar objects by touch alone. When asked to stand erect with feet together and eyes closed, a person with dorsal column damage may sway and fall. This is a positive Romberg sign.
As the contents of the stomach become thoroughly liquefied, they pass into the duodenum, the first segment of the small intestine. The duodenum is the first 10" of the small intestine
Two ducts enter the duodenum:
- one draining the gall bladder and hence the liver
- the other draining the exocrine portion of the pancreas.
From the intestinal mucosal cells, and from the liver and gallbladder. Secretions from the pancreas and bile from the gallbladder enter the duodenum through the hepatopancreatic ampulla and the sphincter of Oddi. These lie where the pancreatic duct and common bile duct join before entering the duodenum. The presence of fatty chyme in the duodenum causes release of the hormone CCK into the bloodstream. CCK is one of the enterogastrones and its main function, besides inhibiting the stomach, is to stimulate the release of enzymes by the pancreas, and the contraction of the gallbladder to release bile. It also stimulates the liver to produce bile. Consumption of excess fat results in excessive bile production by the liver, and this can lead to the formation of gallstones from precipitation of the bile salts.
The acid in the chyme stimulates the release of secretin which causes the pancreas to release bicarbonate which neutralizes the acidity
Concentration versus diluting urine
Kidney is a major route for eliminating fluid from the body to accomplish water balance. Urine excretion is the last step in urine formation. Everyday both kidneys excrete about 1.5 liters of urine.
Depending on the hydrated status of the body, kidney either excretes concentrated urine ( if the plasma is hypertonic like in dehydrated status ) or diluted urine ( if the plasma is hypotonic) .
This occurs thankful to what is known as countercurrent multiplying system, which functions thankfully to establishing large vertical osmotic gradient .
To understand this system, lets review the following facts:
1. Descending limb of loop of Henle is avidly permeable to water.
2. Ascending limb of loop of Henly is permeable to electrolytes , but impermeable to water. So fluid will not folow electrolytes by osmosis.and thus Ascending limb creates hypertonic interstitium that will attract water from descending limb.
Pumping of electrolytes
3. So: There is a countercurrent flow produced by the close proximity of the two limbs.
Juxtamedullary nephrons have long loop of Henle that dips deep in the medulla , so the counter-current system is more obvious and the medullary interstitium is always hypertonic . In addition, peritubular capillaries in the medulla are straigh ( vasa recta) in which flow is rapid and rapidly reabsorb water maintaining hypertonic medullary interstitium.
In distal tubules water is diluted. If plasma is hypertonic, this will lead to release of ADH by hypothalamus, which will cause reabsorption of water in collecting tubules and thus excrete concentrated urine.
If plasma is hypotonic ADH will be inhibited and the diluted urine in distal tubules will be excreted as diluted urine.
Urea contributes to concentrating and diluting of urine as follows:
Urea is totally filtered and then 50% of filtrated urea will be reabsorbed to the interstitium, this will increase the osmolarity of medullary interstitium ( becomes hypertonic ). Those 50% will be secreted in ascending limb of loop of Henle back to tubular fluid to maintain osmolarity of tubular fluid. 55% of urea in distal nephron will be reabsorbed in collecting ducts back to the interstitium ( under the effect of ADH too) . This urea cycle additionally maintain hypertonic interstitium.
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.
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 .
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+)