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 .
COPD and Cancer
A. Chronic Obstructive Pulmonary Disease (COPD)
1. Common features of COPD
a. almost all have smoking history
b. dyspnea - chronic "gasping" for air
c. frequent coughing and infections
d. often leads to respiratory failure
2. obstructive emphysema - usually results from smoking
a. enlargement & deterioration of alveoli
b. loss of elasticity of the lungs
c. "barrel chest" from bronchiole opening during inhalation & constriction during exhalation
3. chronic bronchitis - mucus/inflammation of mucosa
B. Lung Cancer
1. squamous cell carcinoma (20-40%) - epithelium of the bronchi and bronchioles
2. adenocarcinoma (25-35%) - cells of bronchiole glands and cells of the alveoli
3. small cell carcinoma (10-20%) - special lymphocyte-like cells of the bronchi
4. 90% of all lung cancers are in people who smoke or have smoked
Hyperventilation
- Treatments :Rebreath air, hold breath (Increase CO2)
Give oxygen for Hypoxemia
Glomerular filtration
Kidneys receive about 20% of cardiac output , this is called Renal Blood Flow (RBF) which is approximatley 1.1 L of blood. Plasma in this flow is about 625 ml . It is called Renal Plasma Flow (RPF) .
About 20 % of Plasma entering the glomerular capillaries is filtered into the Bowman`s capsule .
Glomerular filtration rate is about 125 ml/min ( which means 7.5 L/hr and thus 180 L/day) This means that the kidney filters about 180 liters of plasma every day.
The urine flow is about 1ml/min ( about 1.5 liter /day) This means that kidney reabsorbs about 178.5 liters every day .
Filtration occurs through the filtration unit , which includes :
1- endothelial cells of glomerular capillaries , which are fenestrated . Fenestrae are quite small so they prevent filtration of blood cells and most of plasma proteins .
2- Glomerular basement membrane : contains proteoglycan that is negatively charged and repels the negatively charged plasma proteins that may pass the fenestrae due to their small molecular weight like albumin . so the membrane plays an important role in impairing filtration of albumin .
3- Epithelial cells of Bowman`s capsule that have podocytes , which interdigitate to form slits .
Many forces drive the glomerular filtration , which are :
1- Hydrostatic pressure of the capillary blood , which favours filtration . It is about 55 mmHg .
2- Oncotic pressure of the plasma proteins in the glomerular capillary ( opposes filtration ) . It is about 30 mm Hg .
3- Hydrostatic pressure of the Bowman`s capsule , which also opposes filtration. It is about 15 mmHg .
The net pressure is as follows :
Hydrostatic pressure of glomerular capillaries - ( Oncotic pressure of glomerular capillaries + Hydrostatic pressure of the Bowman capsule):
55-(35+10)
=55-45
=10 mmHg .
Te glomerular filtration rate does not depend only on the net pressure , but also on an other value , known as filtration coefficient ( Kf) . The later depends on the surface area of the glomerular capillaries and the hydraulic conductivity of the glomerular capillaries.
The Stomach :
The wall of the stomach is lined with millions of gastric glands, which together secrete 400–800 ml of gastric juice at each meal. Three kinds of cells are found in the gastric glands
- parietal cells
- chief cells
- mucus-secreting cells
Parietal cells : secrete
Hydrochloric acid : Parietal cells contain a H+ ATPase. This transmembrane protein secretes H+ ions (protons) by active transport, using the energy of ATP.
Intrinsic factor: Intrinsic factor is a protein that binds ingested vitamin B12 and enables it to be absorbed by the intestine. A deficiency of intrinsic factor as a result of an autoimmune attack against parietal cells causes pernicious anemia.
Chief Cells : The chief cells synthesize and secrete pepsinogen, the precursor to the proteolytic enzyme pepsin.
Secretion by the gastric glands is stimulated by the hormone gastrin. Gastrin is released by endocrine cells in the stomach in response to the arrival of food.
- Sensory:
- Somatic (skin & muscle) Senses:
Postcentral gyrus (parietal lobe). This area senses touch, pressure, pain, hot, cold, & muscle position. The arrangement is upside-down (head below, feet above) and is switched from left to right (sensations from the right side of the body are received on the left side of the cortex). Some areas (face, hands) have many more sensory and motor nerves than others. A drawing of the body parts represented in the postcentral gyrus, scaled to show area, is called a homunculus . - Vision:
Occipital lobe, mostly medial, in calcarine sulcus. Sensations from the left visual field go to the right cortex and vice versa. Like other sensations they are upside down. The visual cortex is very complicated because the eye must take into account shape, color and intensity. - Taste:
Postcentral gyrus, close to lateral sulcus. The taste area is near the area for tongue somatic senses. - Smell:
The olfactory cortex is not as well known as some of the other areas. Nerves for smell go to the olfactory bulb of the frontal cortex, then to other frontal cortex centers- some nerve fibers go directly to these centers, but others come from the thalamus like most other sensory nerves - Hearing:
Temporal lobe, near junction of the central and lateral sulci. Mostly within the lateral sulcus. There is the usual crossover and different tones go to different parts of the cortex. For complex patterns of sounds like speech and music other areas of the cortex become involved.
- Somatic (skin & muscle) Senses:
- Motor:
- Primary Motor ( Muscle Control):
Precentral gyrus (frontal lobe). Arranged like a piano keyboard: stimulation in this area will cause individual muscles to contract. Like the sensory cortex, the arrangement is in the form of an upside-down homunculus. The fibers are crossed- stimulation of the right cortex will cause contraction of a muscle on the left side of the body. - Premotor (Patterns of Muscle Contraction):
Frontal lobe in front of precentral gyrus. This area helps set up learned patterns of muscle contraction (think of walking or running which involve many muscles contracting in just the right order). - Speech-Muscle Control:
Broca's area, frontal lobe, usually in left hemisphere only. This area helps control the patterns of muscle contraction necessary for speech. Disorders in speaking are called aphasias.
- Primary Motor ( Muscle Control):
- Perception:
- Speech- Comprehension:
Wernicke's area, posterior end of temporal lobe, usually left hemisphere only. Thinking about words also involves areas in the frontal lobe. - Speech- Sound/Vision Association:
Angular gyrus, , makes connections between sounds and shapes of words
- Speech- Comprehension:
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.