NEET MDS Lessons
Physiology
Serum Proteins
Proteins make up 6–8% of the blood. They are about equally divided between serum albumin and a great variety of serum globulins.
After blood is withdrawn from a vein and allowed to clot, the clot slowly shrinks. As it does so, a clear fluid called serum is squeezed out. Thus:
Serum is blood plasma without fibrinogen and other clotting factors.
The serum proteins can be separated by electrophoresis.
- The most prominent of these and the one that moves closest to the positive electrode is serum albumin.
- Serum albumin
- is made in the liver
- binds many small molecules for transport through the blood
- helps maintain the osmotic pressure of the blood
- The other proteins are the various serum globulins.
- alpha globulins (e.g., the proteins that transport thyroxine and retinol [vitamin A])
- beta globulins (e.g., the iron-transporting protein transferrin)
- gamma globulins.
- Gamma globulins are the least negatively-charged serum proteins. (They are so weakly charged, in fact, that some are swept in the flow of buffer back toward the negative electrode.)
- Most antibodies are gamma globulins.
- Therefore gamma globulins become more abundant following infections or immunizations.
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 .
Hypoxia
- Hypoxia is tissue oxygen deficiency
- Brain is the most sensitive tissue to hypoxia: complete lack of oxygen can cause unconsciousness in 15 sec and irreversible damage within 2 min.
- Oxygen delivery and use can be interrupted at several sites
Type of |
O2 Uptake |
Hemoglobin |
Circulation |
Tissue O2 Utilization |
Hypoxic |
Low |
Normal |
Normal |
Normal |
Anemic |
Normal |
Low |
Normal |
Normal |
Ischemic |
Normal |
Normal |
Low |
Normal |
Histotoxic |
Normal |
Normal |
Normal |
Low |
- Causes:
- Hypoxic: high altitude, pulmonary edema, hypoventilation, emphysema, collapsed lung
- Anemic: iron deficiency, hemoglobin mutations, carbon monoxide poisoning
- Ischemic: shock, heart failure, embolism
- Histotoxic: cyanide poisoning (inhibits mitochondria)
- Carbon monoxide (CO) poisoning:
- CO binds to the same heme Fe atoms that O2 binds to
- CO displaces oxygen from hemoglobin because it has a 200X greater affinity for hemoglobin.
- Treatment for CO poisoning: move victim to fresh air. Breathing pure O2 can give faster removal of CO
- Cyanide poisoning:
- Cyanide inhibits the cytochrome oxidase enzyme of mitochondria
- Two step treatment for cyanide poisoning:
- 1) Give nitrites
- Nitrites convert some hemoglobin to methemoglobin. Methemoglobin pulls cyanide away from mitochondria.
- 2) Give thiosulfate.
- Thiosulfate converts the cyanide to less poisonous thiocyanate.
- 1) Give nitrites
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.
Plasma: is the straw-colored liquid in which the blood cells are suspended.
Composition of blood plasma |
|
Component |
Percent |
Water |
~92 |
Proteins |
6–8 |
Salts |
0.8 |
Lipids |
0.6 |
Glucose (blood sugar) |
0.1 |
Plasma transports materials needed by cells and materials that must be removed from cells:
- various ions (Na+, Ca2+, HCO3−, etc.
- glucose and traces of other sugars
- amino acids
- other organic acids
- cholesterol and other lipids
- hormones
- urea and other wastes
Most of these materials are in transit from a place where they are added to the blood
- exchange organs like the intestine
- depots of materials like the liver
to places where they will be removed from the blood.
- every cell
- exchange organs like the kidney, and skin.
Blood is a liquid tissue. Suspended in the watery plasma are seven types of cells and cell fragments.
- red blood cells (RBCs) or erythrocytes
- platelets or thrombocytes
- five kinds of white blood cells (WBCs) or leukocytes
- Three kinds of granulocytes
- neutrophils
- eosinophils
- basophils
- Two kinds of leukocytes without granules in their cytoplasm
- lymphocytes
- monocytes
- Three kinds of granulocytes
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.