NEET MDS Lessons
Physiology
Clinical Physiology
Heart Failure : Heart failure is inability of the heart to pump the enough amount of blood needed to sustain the needs of organism .
It is usually called congestive heart failure ( CHF) .
To understand the pathophysiology of the heart failure , lets compare it with the physiology of the cardiac output :
Cardiac output =Heart rate X stroke volume
Stroke volume is determined by three determinants : Preload ( venous return ) , contractility , and afterload (peripheral resistance ) . Any disorder of these factors will reduce the ability of the heart to pump blood .
Preload : Any factor that decrease the venous return , either by decreasing the intravenous pressure or increasing the intraatrial pressure will lead to heart failure .
Contractility : Reducing the power of contraction such as in myocarditis , cardiomyopathy , preicardial tamponade ..etc , will lead to heart failure .
Afterload : Any factor that may increase the peripheral resistance such as hypertension , valvular diseases of the heart may cause heart failure.
Pathophysiology : When the heart needs to contract more to meet the increased demand , compensatory mechanisms start to develope to enhance the power of contractility . One of these mechanism is increasing heart rate , which will worsen the situation because this will increase the demands of the myocardial cells themselves . The other one is hypertrophy of the cardiac muscle which may compensate the failure temporarily but then the hypertrophy will be an additional load as the fibers became stiff .
The stroke volume will be reduced , the intraventricular pressure will increase and consequently the intraatrial pressure and then the venous pressure . This will lead to decrease reabsorption of water from the interstitium ( see microcirculation) and then leads to developing of edema ( Pulmonary edema if the failure is left , and systemic edema if the failure is right) .
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 .
The Nervous System Has Peripheral and Central Units
- The central nervous system (CNS) is the brain and spinal column
- The peripheral nervous system (PNS) consists of nerves outside of the CNS
- There are 31 pairs of spinal nerves (mixed motor & sensory)
- There are 12 pairs of cranial nerves (some are pure sensory, but most are mixed)
The pattern of innervation plotted on the skin is called a dermatome
The Nervous System Has Peripheral and Central Units
- The central nervous system (CNS) is the brain and spinal column
- The peripheral nervous system (PNS) consists of nerves outside of the CNS
- There are 31 pairs of spinal nerves (mixed motor & sensory)
- There are 12 pairs of cranial nerves (some are pure sensory, but most are mixed)
The pattern of innervation plotted on the skin is called a dermatome
Tubular secretion:
Involves transfer of substances from peritubular capillaries into the tubular lumen. It involves transepithelial transport in a direction opposite to that of tubular absorption.
Renal tubules can selectively add some substances that have not been filtered to the substances that already have been filtered via tubular secretion.
Tubular secretion mostly function to eliminate foreign organic ions, hydrogen ions ( as a contribution to acid base balance ), potassium ions ( as a contribution to maintaining optimal plasma K+ level to assure normal proceeding of neural and muscular functions), and urea.
Here we will focus on K+ secretion and will later discuss H+ secretion in acid base balance, while urea secretion will be discussed in water balance.
K+ is filtered in glomerular capillaries and then reabsorbed in proximal convoluted tubules as well as in thick ascending limb of loop of Henley ( Na-2Cl-K symporter)
K+ secretion takes place in collecting tubules (distal nephron) . There are two types of cells in distal nephron:
- Principal cells that reabsorb sodium and secrete K+ .
- Intercalated cells that reabsorb K+ in exchange with H+.
Mechanism of secretion of K+ in principal cells : Two steps
- K+ enters tubular cells by Na/K ATPase on the basolateral membrane.
- K+ leaves the tubular cells via K+ channels in apical membrane.
Aldosterone is a necessary regulatory factor.
If there is increased level of K+ in plasma,excessive K+ is secreted , some of which is reabsorbed back to the plasma in exchange with H+ via the intercalated cells.
Functions
Manufacture - blood proteins - albumen, clotting proteins , urea - nitrogenous waste from amino acid metabolism , bile - excretory for the bile pigments, emulsification of fats by bile salts
Storage - glycogen , iron - as hemosiderin and ferritin , fat soluble vitamins A, D, E, K
Detoxification -alcohol , drugs and medicines , environmental toxins
Protein metabolism -
- transamination - removing the amine from one amino acid and using it to produce a different amino acid. The body can produce all but the essential amino acids; these must be included in the diet.
- deamination - removal of the amine group in order to catabolize the remaining keto acid. The amine group enters the blood as urea which is excreted through the kidneys.
Glycemic Regulation - the management of blood glucose.
- glycogenesis - the conversion of glucose into glycogen.
- glycogenolysis - the breakdown of glycogen into glucose.
gluconeogenesis - the manufacture of glucose from non carbohydrate sources, mostly protein
The pancreas
The pancreas consists of clusters if endocrine cells (the islets of Langerhans) and exocrine cells whose secretions drain into the duodenum.
Pancreatic fluid contains:
- sodium bicarbonate (NaHCO3). This neutralizes the acidity of the fluid arriving from the stomach raising its pH to about 8.
- pancreatic amylase. This enzyme hydrolyzes starch into a mixture of maltose and glucose.
- pancreatic lipase. The enzyme hydrolyzes ingested fats into a mixture of fatty acids and monoglycerides. Its action is enhanced by the detergent effect of bile.
- 4 zymogens— proteins that are precursors to active proteases. These are immediately converted into the active proteolytic enzymes:
- trypsin. Trypsin cleaves peptide bonds on the C-terminal side of arginines and lysines.
- chymotrypsin. Chymotrypsin cuts on the C-terminal side of tyrosine, phenylalanine, and tryptophan residues (the same bonds as pepsin, whose action ceases when the NaHCO3 raises the pH of the intestinal contents).
- elastase. Elastase cuts peptide bonds next to small, uncharged side chains such as those of alanine and serine.
- carboxypeptidase. This enzyme removes, one by one, the amino acids at the C-terminal of peptides.
- nucleases. These hydrolyze ingested nucleic acids (RNA and DNA) into their component nucleotides.
The secretion of pancreatic fluid is controlled by two hormones:
- secretin, which mainly affects the release of sodium bicarbonate, and
- cholecystokinin (CCK), which stimulates the release of the digestive enzymes.