NEET MDS Lessons
Physiology
Biological Functions are Extremely Sensitive to pH
- H+ and OH- ions get special attention because they are very reactive
- Substance which donates H+ ions to solution = acid
- Substance which donates OH- ions to solution = base
- Because we deal with H ions over a very wide range of concentration, physiologists have devised a logarithmic unit, pH, to deal with it
- pH = - log [H+]
- [H+] is the H ion concentration in moles/liter
- Because of the way it is defined a high pH indicates low H ion and a low pH indicates high H ion- it takes a while to get used to the strange definition
- Also because of the way it is defined, a change of 1 pH unit means a 10X change in the concentration of H ions
- If pH changes by 2 units the H+ concentration changes by 10 X 10 = 100 times
- Human blood pH is 7.4
- Blood pH above 7.4 = alkalosis
- Blood pH below 7.4 = acidosis
- Body must get rid of ~15 moles of potential acid/day (mostly CO2)
- CO2 reacts with water to form carbonic acid (H2CO3)
- Done mostly by lungs & kidney
- In neutralization H+ and OH- react to form water
- If the pH changes charges on molecules also change, especially charges on proteins
- This changes the reactivity of proteins such as enzymes
- Large pH changes occur as food passes through the intestines.
Cell, or Plasma, membrane
- Structure - 2 primary building blocks include
protein (about 60% of the membrane) and lipid, or
fat (about 40% of the membrane).
The primary lipid is called phospholipids, and molecules of phospholipid form a 'phospholipid bilayer' (two layers of phospholipid molecules). This bilayer forms because the two 'ends' of phospholipid molecules have very different characteristics: one end is polar (or hydrophilic) and one (the hydrocarbon tails below) is non-polar (or hydrophobic):
- Functions include:
- supporting and retaining the cytoplasm
- being a selective barrier .
- transport
- communication (via receptors)
Ingestion: Food taken in the mouth is
- ground into finer particles by the teeth,
- moistened and lubricated by saliva (secreted by three pairs of salivary glands)
- small amounts of starch are digested by the amylase present in saliva
- the resulting bolus of food is swallowed into the esophagus and
- carried by peristalsis to the stomach.
The Body Regulates pH in Several Ways
- Buffers are weak acid mixtures (such as bicarbonate/CO2) which minimize pH change
- Buffer is always a mixture of 2 compounds
- One compound takes up H ions if there are too many (H acceptor)
- The second compound releases H ions if there are not enough (H donor)
- The strength of a buffer is given by the buffer capacity
- Buffer capacity is proportional to the buffer concentration and to a parameter known as the pK
- Mouth bacteria produce acids which attack teeth, producing caries (cavities). People with low buffer capacities in their saliva have more caries than those with high buffer capacities.
- Buffer is always a mixture of 2 compounds
- CO2 gas (a potential acid) is eliminated by the lungs
- Other acids and bases are eliminated by the kidneys
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 .
Oxygen Transport in Blood: Hemoglobin
A. Association & Dissociation of Oxygen + Hemoglobin
1. oxyhemoglobin (HbO2) - oxygen molecule bound
2. deoxyhemoglobin (HHb) - oxygen unbound
H-Hb + O2 <= === => HbO2 + H+
3. binding gets more efficient as each O2 binds
4. release gets easier as each O2 is released
5. Several factors regulate AFFINITY of O2
a. Partial Pressure of O2
b. temperature
c. blood pH (acidity)
d. concentration of “diphosphoglycerate” (DPG)
B. Effects of Partial Pressure of O2
1. oxygen-hemoglobin dissociation curve
a. 104 mm (lungs) - 100% saturation (20 ml/100 ml)
b. 40 mm (tissues) - 75% saturation (15 ml/100 ml)
c. right shift - Decreased Affinity, more O2 unloaded
d. left shift- Increased Affinity, less O2 unloaded
C. Effects of Temperature
1. HIGHER Temperature --> Decreased Affinity (right)
2. LOWER Temperature --> Increased Affinity (left)
D. Effects of pH (Acidity)
1. HIGHER pH --> Increased Affinity (left)
2. LOWER pH --> Decreased Affinity (right) "Bohr Effect"
a. more Carbon Dioxide, lower pH (more H+), more O2 release
E. Effects of Diphosphoglycerate (DPG)
1. DPG - produced by anaerobic processes in RBCs
2. HIGHER DPG > Decreased Affinity (right)
3. thyroxine, testosterone, epinephrine, NE - increase RBC metabolism and DPG production, cause RIGHT shift
F. Oxygen Transport Problems
1. hypoxia - below normal delivery of Oxygen
a. anemic hypoxia - low RBC or hemoglobin
b. stagnant hypoxia - impaired/blocked blood flow
c. hypoxemic hypoxia - poor lung gas exchange
2. carbon monoxide poisoning - CO has greater Affinity than Oxygen or Carbon Dioxide
The defecation reflex:
As a result of the mass movements, pressure is exerted on the rectum and on the internal anal sphincter, which is smooth muscle, resulting in its involuntary relaxation. Afferent impulses are sent to the brain indicating the need to defecate. The external sphincter is voluntary muscle and is controlled by the voluntary nervous system. This sphincter is relaxed along with contraction of the rectal and abdominal muscles in the defecation reflex