Rest Of Physiology Flashcards
Calcium homeostasis
Serum calcium levels are maintained under tight regulatory control. When serum levels become low, parathyroid hormone secretion is stimulated which results in calcium release from bone, increased intestinal absorption, and increased renal resorption. Osteoclasts are responsible for bone breakdown and calcium release. Vitamin D plays an important role in maintaining calcium levels through intestinal absorption and renal resorption. The hypermetabolic state of hyperthyroidism can lead to mild to moderate increases in serum calcium levels. Calcitonin is released by the parafollicular C cells of the thyroid gland and it opposes the effect of parathyroid hormone. It inhibits osteoclast activity and renal calcium resorption.
Calcium is absorbed from the intestinal lumen by two distinct mechanisms: active transcellular absorption in the duodenum when calcium intake is low, and passive paracellular absorption in the jejunum and ileum if calcium levels are high. In active absorption, calcium is carried by calbindin, a vitamin-D–dependent calcium-binding protein. If Ca2+ levels are low, calcitriol production will be increased to enhance the rate of calcium absorption. Low PTH levels in the blood such as post parathyroidectomy indirectly inhibit calcium absorption from the gut by inhibiting the conversion of cholecalciferol into calcitriol.
Body response to hypoglycaemia
When the blood glucose level drops, a cascade of physiological responses takes place. A blood glucose level between 70 and 100 mg/dL supresses insulin release. Symptoms of hypoglycaemia, e.g. cold sweats, dizziness, shaking and weakness, occur at this stage. A further drop (50–70 mg/dL) results in the release of several hormones, i.e. glucagon, epinephrine, cortisol and growth hormone. Neurogenic symptoms (i.e. irritability, lack of concentration, or behavioural changes) occur at this stage. The glucose threshold essential for activation of counter-regulatory hormones is always higher than the threshold of symptom occurrence.
Sympathetic receptors
The autonomic nervous system has two divisions: sympathetic and parasympathetic. The sympathetic nervous system (SNS) has a thoracolumbar location, and most sympathetic postganglionic fibers release norepinephrine. Adrenergic receptors (alpha- and beta-receptors) are targets of catecholamines like norepinephrine and epinephrine. Stimulation of alpha-1 receptors causes peripheral vasoconstriction and mydriasis. Stimulation of beta-2 receptors causes relaxation of smooth muscle in the vasculature and bronchi, whereas stimulation of beta-3 receptors stimulates lipolysis. Stimulation of alpha-2 receptors inhibits insulin secretion and lipolysis.
The adrenergic receptors or “adrenoceptors” are a class of G protein-coupled receptors that are targets of many catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) produced by the body. There are two main groups of adrenoreceptors: alpha and beta. Each contains many sub-groups (α1, α2, β1, β2, β3). Glycogenolysis is caused by stimulation in the α1 and β2 receptors.
Thermoregulatory system
An increase in the set-point of the thermoregulatory system will most likely cause the body temperature to remain above normal. Exogenous pyrogens or endogenous pyrogens (e.g. prostaglandin E2) act on the hypothalamus, stimulating the pre-optic nucleus and resulting in an increase in body temperature. An increase in the intensity of exercise, hyperthyroidism, and a decrease in evaporative water loss will result in hyperthermia rather than fever.
The core body temperature is primarily regulated by environmental temperature and the rate of cellular heat production. Heat loss from the body occurs through four mechanisms: evaporation, convection, conduction, and radiation. Radiation and conduction are responsible for approximately 65% of the loss under average conditions. Evaporation is the next primary source of heat loss, accounting for approximately 22%. In individuals with extremely high skin temperature (over 43⁰C), evaporation is the only mechanism of heat dissipation.
Metabolism in body
All human cells require ATP to function normally. ATP is carefully produced from energy-rich molecules like glucose, free fatty acids and proteins. Aerobic cellular respiration includes three energy systems: glycolysis, the Krebs cycle, and oxidative phosphorylation. Cellular respiration is regulated mainly by the availability of critical substrates such as inorganic phosphate, ATP, ADP, and AMP. Among those substrates, ADP is the rate-limiting factor for almost all energy metabolism in the human body.
Glucose transport in body
Glucose is transported by different mechanisms in the human body. In the gastrointestinal tract, glucose is transported across intestinal epithelial cells by primary active transport. This is essential to ensure that glucose is transported in a one-way manner from the gut lumen to the blood and not vice versa, regardless of the concentration gradient. Most of the other body cells use facilitated diffusion for glucose transport. In facilitated diffusion, glucose is transported by “carriers” from blood to cells and vice versa according to the concentration gradient to maintain glucose homeostasis and body energy supply.
Anaerobic exercise
In anaerobic conditions, pyruvate is metabolized to lactic acid in the muscles. Lactic acid is taken up by the liver and converted to glucose (gluconeogenesis) during the Cori cycle. Hepatic glucose is then released to the bloodstream and returns to the muscles to be cyclically metabolized back to lactic acid. Pyruvate is the first substrate of the gluconeogenic pathway but is finally used to generate glucose. Although triacylglycerol, alanine, and glutamine can be used as substrates for gluconeogenesis, they are not part of the Cori cycle.
Cell Cycle
The resting cell is in Gap 0 (G0). During G1, protein synthesis increases and the cell grows in size. DNA replication occurs during the synthesis (S) phase of the cell cycle. A further period of protein synthesis and growth follows in G2 as the cell prepares for mitosis. Mitosis occurs during the M phase.
Plasma Cholesterol
Plasma cholesterol is regulated by genes, diet, hormones, and lipoproteins. The primary cholesterol-carrying lipoproteins are low-density lipoproteins (LDLs) and high-density lipoproteins (HDLs). Biliary obstruction (particularly primary biliary cirrhosis), diabetes mellitus, moderate to high intake of dietary amounts of cholesterol, and hypothyroidism can increase plasma cholesterol. Statins are HMG-CoA reductase inhibitors, widely used to decrease circulating LDL and triglycerides. Statins modestly increase HDL levels.
In fatty acid metabolism, acetyl-CoA formed by beta-oxidation of fatty acids can be synthesized to cholesterol and other steroids. Its hydrophilic nature requires cholesterol to be transported effectively by lipoproteins such as chylomicrons, but it only constitutes a very small portion (1%–3%) compared to other components. Dietary cholesterol is transported to the liver by chylomicron remnants. Cholesterol levels are regulated by negative feedback to HMG-CoA reductase and thyroid hormone. T3 and some TH mimetic compounds reduce the plasma concentration of cholesterol by increasing hepatic uptake and conversion to bile acids.
Essential micronutrients
Essential micronutrients play a central role in metabolic homeostasis, and adequate intake is necessary for proper maintenance of tissue function. Inorganic micronutrients include cobalt, selenium, zinc, and copper. Organic micronutrients include fat-soluble and water-soluble vitamins. Zinc regulates the transcription of receptors for steroid hormones and is an essential cofactor for over 100 enzymes. Selenium is required in the form of selenocysteine within the enzyme glutathione peroxidase, and deficiency may cause cardiomyopathy. Strontium is not considered an essential micronutrient.
BGL regulation
Blood glucose level is regulated by various factors. Several hormones are involved in the regulation of blood glucose. Insulin and somatostatin reduce the blood glucose level (known as “hypoglycaemic factors”), whilst glucagon, epinephrine, cortisol, adrenocorticotrophic hormone, growth hormone and thyroxine increase blood glucose levels (known as “hyperglycaemic factors”). Other hypoglycaemic factors include exercise, hepatic storage of glycogen, fat synthesis, and renal excretion of glucose. Other hyperglycaemic factors include hepatic glycogen breakdown, protein catabolism, and intestinal glucose absorption.
Excessive thyroid hormone causes increased glucose production in the liver, rapid absorption of glucose through the intestines, and increased insulin resistance.
Catecholamines cause an increase in blood sugar by α-agonism, by decreasing insulin secretion and glycogenolysis.
Growth hormone in general counteracts the insulin effects on glucose and lipid metabolism but has anabolic properties on proteins.
Mild to moderate exercise causes an increase in heart rate which causes the muscles to use more glucose.
SDA
Protein > Carbohydrate
Insulin secretion
There are diverse inhibitors and potentiators of insulin secretion in the human body. Insulin secretion is inhibited by somatostatin, peptide YY, neuropeptide Y, pancreatic polypeptide and certain medications, e.g. propranolol and thiazide diuretics. On the other hand, it is stimulated by glucagon, acetylcholine, gastrin-releasing peptide, vasoactive intestinal peptide, epinephrine and some drugs, e.g. salbutamol.
During the fasted state, body blood glucose will be maintained in many ways with the help of glucagon. First, the liver and muscle will break down glycogen into glucose (glycogenolysis). The liver will also produce “new glucose” through gluconeogenesis. In this process, amino acids and glycerol will be converted into glucose. The waste product of gluconeogenesis is urea. A high level of urea will then be excreted via urine. In prolonged fasting, the liver will also produce a high level of ketone bodies from free fatty acids as an alternative energy source besides glucose. Following approximately 1 week of fasting, cells will use ketone bodies as their main energy source, rather than glucose (70%:30%). The respiratory quotient of ketone bodies is lower than that of glucose, so the total RQ will be decreased. The increase of ketone bodies and urea in the blood will increase blood acidity and consequently increase urine acidity.
Hormones and Neurotransmitters
Hormones and neurotransmitters are chemical signalling molecules produced by the human body. The main differences between hormones and neurotransmitters are as follows:
- Hormones are produced by endocrine glands and released into the blood stream, whilst neurotransmitters are released by presynaptic nerve terminals into the synaptic gap.
- The targets of hormones are distant from the origin of hormonal production whereas neurotransmitters act on neighbouring postsynaptic nerve endings.
- Hormones can be proteins or lipids whilst neurotransmitters are proteins. Examples of amino acids that can act as neurotransmitters or hormones include serotonin, norepinephrine, epinephrine, L-DOPA, thyroxin, oxytocin, glutamate, histamine and acetylcholine.
Aromatic amino acids (tryptophan, tyrosine, phenylalanine) are biosynthetic precursors for some hormones and neurotransmitters including epinephrine, norepinephrine, dopamine, serotonin, and thyroxine.
Aldosterone is not an amino acid. It is a steroid hormone produced by the adrenal gland, and is involved in regulation of blood pressure and electrolytes. It helps in the conservation of sodium by the kidneys, sweat glands, salivary glands, and colon. It is a part of the renin–angiotensin–aldosterone system.
Fasted State
During the fasted state, body blood glucose will be maintained in many ways with the help of glucagon. First, the liver and muscle will break down glycogen into glucose (glycogenolysis). The liver will also produce “new glucose” through gluconeogenesis. In this process, amino acids and glycerol will be converted into glucose. The waste product of gluconeogenesis is urea. A high level of urea will then be excreted via urine. In prolonged fasting, the liver will also produce a high level of ketone bodies from free fatty acids as an alternative energy source besides glucose. Following approximately 1 week of fasting, cells will use ketone bodies as their main energy source, rather than glucose (70%:30%). The respiratory quotient of ketone bodies is lower than that of glucose, so the total RQ will be decreased. The increase of ketone bodies and urea in the blood will increase blood acidity and consequently increase urine acidity.
Insulin
The effects of insulin on adipose tissues include:
- Increased glucose entry
- Increased fatty acid synthesis and lipogenesis
- Increased glycerol phosphate synthesis
- Increased triglyceride deposition
- Activation of lipoprotein lipase
- Inhibition of hormone-sensitive lipase
- Increased K+ uptake
Insulin acts mainly on liver, muscle, and adipose tissues.
It promotes formation of glycogen from glucose both in the liver and muscles.
It stimulates amino acid uptake into cells, increases protein synthesis, and inhibits protein degradation in liver and muscles.
It increases K+ uptake into cells, thereby decreasing blood [K+].
Ketogenesis is the production of ketone bodies from fatty acids. Insulin inhibits hormone-sensitive lipase and activates acetyl-coA carboxylase, thereby inhibiting lipolysis.
Insulin stimulates the lipoprotein lipase in fatty tissues to break down the triglycerides into smaller fatty acids and monoglycerides, which can either be used as a fuel or reassembled as triglycerides for storage in the liver.
Insulin increases the glycogenesis (formation of glycogen) and decreases the glycogenolysis (breakdown of glycogen) in the muscles and liver, in order to control the blood glucose level, by storing it as glycogen.
Ketogenesis is the production of ketone bodies from fatty acids in the body to use as a fuel in case of low blood sugar. Insulin inhibits hormone-sensitive lipase and activates acetyl-CoA carboxylase, thereby reducing the starting material for fatty acids.
Absence or low levels of insulin promote widespread catabolism, especially of body fat cells and proteins.
It causes increased levels of glucose in the blood.
It leads to activation of hormone-sensitive lipase which causes lipolysis.
It causes a decrease in the pH levels of blood.
Fat breakdown occurs for energy production. In the absence of insulin, hormone-sensitive lipase is activated. This results in the release of glycerol and fatty acids into the circulation. In the liver, the excess fatty acids are transported into the mitochondria and beta-oxidized. This produces a large quantity of acetyl-CoA, which exceeds the body’s ability to utilise it in the citric acid cycle, and is, thus, transformed into acetoacetic acid. This is then secreted into circulation resulting in acidosis (low pH).
Retention of Na
Associated with
Rise in capillary pressure
Increase in percentage of total body water in ECF
Haemorrhage
First 3-5 days after a major surgical operation
Essential Fatty acids
Essential fatty acids are fatty acids that humans and other animals require for maintaining health, but are unable to synthesize. Humans and other animals must gain EFAs from their diet. There are only two fatty acids that are considered as EFAs in humans. These are alpha-linolenic acid (an omega-3 fatty acid) and linoleic acid (an omega-6 fatty acid).
Uric Acid
Uric acid is the end product of an exogenous pool of purines and endogenous purine metabolism. This long process involves the conversion of two purine nucleic acids—adenine and guanine—by several enzymes. Adenine monophosphate (AMP) is converted to inosine and then hypoxanthine while guanine monophosphate (GMP) forms guanosine and then guanine. These two pathways join by their conversion to xanthine, and finally form uric acid, by catalysation of xanthine oxidase.
Reabsorption of HCO3
85% of filtered HCO3- is reabsorbed in the proximal tubule. HCO3- is reabsorbed from the cells into the blood via the Na+/HCO3- cotransporter. In a hyperkalemic state, K+ secretion from the blood to the cells via Na+/K+-ATPase will be increased. This causes intracellular Na+ to decrease, thus decreasing Na+/HCO3- cotransporter action.
Total Pancreatectomy
The pancreas has exocrine and endocrine functions. Exocrine functions are mediated by acinar cells that secrete digestive enzymes into the duodenum via the pancreatic duct. Endocrine functions are mediated by cells located in islets of Langerhans, which secrete glucagon, insulin, somatostatin, ghrelin, and pancreatic polypeptide. Total pancreatectomy will result in pancreatic exocrine deficiency resulting in steatorrhea. It will also cause a decrease in the plasma insulin level, resulting in decreased plasma PCO2 and a decrease in plasma glucagon levels.
FFA’s
The pancreas has exocrine and endocrine functions. Exocrine functions are mediated by acinar cells that secrete digestive enzymes into the duodenum via the pancreatic duct. Endocrine functions are mediated by cells located in islets of Langerhans, which secrete glucagon, insulin, somatostatin, ghrelin, and pancreatic polypeptide. Total pancreatectomy will result in pancreatic exocrine deficiency resulting in steatorrhea. It will also cause a decrease in the plasma insulin level, resulting in decreased plasma PCO2 and a decrease in plasma glucagon levels.
Ketone bodies
Hepatic production of ketone bodies occurs during fasting and prolonged exercise. While skeletal muscle can readily metabolize ketone bodies in the citric acid cycle, CNS cells only use ketone bodies during periods where glucose is not readily available. Ketone bodies can be formed from the metabolism of ketogenic amino acids (e.g. leucine and lysine) as well as from the breakdown of pyruvate. The depletion of citric acid cycle intermediates (mainly oxaloacetate) results in the accumulation of acetyl-CoA and activation ketogenesis.
Vitamin B12
Cobalamin (B12) is a water-soluble vitamin essential for DNA synthesis and replications, and cellular energy production. It is found in animal products such as meat, dairy products, eggs, fish, and shellfish. The presence of trypsin facilitates cobalamin absorption, and intrinsic factor is required for the absorption of B12 in the terminal ileum. Serum vitamin B12 is carried by proteins known as “transcobalamins” (TC). Cobalamin deficiency results in megaloblastic anemia and neurologic findings.
Most abundant minerals in body
Phosphorus, along with calcium, is an abundant essential mineral present in foods and available as a dietary supplement. Approximately 85% of the phosphorus contained in phosphate is found in bones and teeth. The kidney is a primary regulator of phosphorus and can increase or decrease its reabsorptive capacity across the proximal renal tubule. Sulphur is the third most abundant essential mineral found in the human body. Sodium, potassium, and chloride are electrolytes responsible for maintaining electrical neutrality in the cells.
Metformin
Metformin is one of the most common medications used for treatment of hyperglycaemia and diabetes mellitus type II. It acts via several mechanisms. It reduces absorption of glucose from the intestine, reduces hepatic gluconeogenesis (formation of new glucose), enhances insulin sensitivity of different tissue cells, and stimulates the uptake and utilization of blood glucose by various body cells.
Carbohydrates
Carbohydrates are the main source of energy in the human body. They are broken down to hexoses, i.e. glucose, fructose and galactose, before absorption at the intestine. They are absorbed at the small intestine to the liver, where galactose and fructose are metabolised to glucose. Approximately 5% of glucose in the liver is converted into glycogen in a process called “glycogenesis”. The synthesised glycogen is stored in hepatocytes and myocytes. When these cells are fully saturated with glycogen, excess glucose is converted into fat.
Calcitonin
Calcitonin is a hormone produced by parafollicular cells of the thyroid gland. Calcitonin’s main effect is to decrease calcium levels in the blood by inhibiting bone reabsorption. Calcitonin also inhibits calcium and phosphate reabsorption in the kidney, thereby increasing urine excretion of both. Calcitonin will be secreted when the calcium blood level is increased (normal = 2.1–2.6 mmol/L).
Magnesium
Magnesium is an essential element in biological systems. Magnesium occurs typically as the Mg2+ ion. Inside the human body, magnesium has many important functions. Magnesium is required to stabilize the genomic structure in DNA and RNA. Magnesium ions are also required for the association of ribosomal subunits. Mg2+ also increases 2-oxoglutarate dehydrogenase (2-OGDH) activity, an enzyme that is important for oxidative phosphorylation. Mg also affects a number of neurotransmitter systems. It inhibits the release of excitatory neurotransmitters and also acts as a voltage-gated antagonist at the glutamate N-methyl-D- aspartate (NMDA) receptor.
Pupillary Dilation
Mydriasis, or pupillary dilation, is caused by the contraction of radial fibers of the iris and relaxation of the sphincter muscle of the iris. The pupillary dilation pathway is a three-neuron pathway caused by sympathetic nerve discharge. The pupillary dilation pathway begins in the hypothalamus with the first-order neuron, which descends through the midbrain to synapse onto the spinal ciliospinal center of Budge (second-order neuron). Then the second-order preganglionic neuron synapses onto the third-order postganglionic neuron at the superior cervical ganglion. Finally, the third-order neuron enters the orbit to synapse on the iris dilator muscle. The Edinger–Westphal nucleus is a parasympathetic preganglionic nucleus, which supplies parasympathetic fibers to the eye and causes pupillary constriction.
Synaptic Terminal
In the presynaptic terminal, the action potential (an electrical signal) is converted into a chemical signal (neurotransmitter release). The amount of neurotransmitter released at the synapse depends on the extracellular Ca2+, and the neurotransmitter quickly diffuses across the synaptic cleft and binds to receptors on the postsynaptic membrane. Neurotransmitters can be excitatory or inhibitory. GABA is an example of an inhibitory neurotransmitter that increases the conductance of the postsynaptic membrane to Cl-.
Gamma motor neurons
Gamma motor neurons (GMNs) are lower motor neurons that maintain 1a afferent activity during contraction of the muscle. GMNs also regulate the gain of the muscle stretch reflex by adjusting the level of tension in the intrafusal muscle fibers of the stretch receptors, or muscle spindles. GMNs help to regulate muscle length and tone but do not detect the length of resting skeletal muscle. The action potential stimulates skeletal muscle fibers to contract by depolarizing the plasma membrane. The Golgi tendon reflex prevents the muscle from producing too much force.
SNS stimulation
Stimulation of the sympathetic nervous system leads to:
- Pupil dilation
- Arteriole constriction
- Bronchial smooth muscle relaxation
- Urinary sphincter contraction
- Reduced saliva production
- Lipolysis
Glucose brain uptake
Glucose uptake in the brain is insulin independent. The brain can make energy from fats or amino acids. Respiratory quotient for cerebral tissue is very high, around 0.95 to 0.99.
Eye
Closed-angle glaucoma results from expansion of the iris to the back of the cornea, where it obliterates the filtration angle and prevents outflow of aqueous humour.
Rhodopsin is the photosensitive pigment found in the rods.
Light must pass through the ganglion and bipolar cells to reach the rods and cones
The retina contains 20 times more rod than cone cells. Cones are most abundant in the macula lutea in the center of the retina. Rod cells are specialized for night vision, whereas cone cells are for day vision. There are three different photopigments in each cone type, allowing the brain to discriminate colours.
Layers of cerebral cortex
From the outermost layer to the innermost layer, the neocortex is composed of the:
- Molecular layer
- External granule cell layer
- External pyramidal cell layer
- Internal granule cell layer
- Internal pyramidal cell layer
- Multiform layer
Basal ganglia disease
Huntington’s disease occurs due to loss of the GABA-mediated inhibitory projections to the globus pallidus resulting in hyperkinesis. It is autosomal dominant.
Wilson disease occurs as a consequence of abnormal copper metabolism which can lead to degeneration of the putamen.
Parkinson’s occurs due to a loss of dopaminergic neurons
The striatum is composed of the putamen and globus pallidus. Outputs from the basal ganglia project to the thalamus. The prefrontal and premotor cortices may receive excitatory projections from the thalamus.
Spinal shock
Spinal shock is divided into 4 major phases:
Phase 1 (hyporeflexia/areflexia) is characterized by complete loss or weakening of all reflexes below the level of injury.
Phase 2 occurs in the next two days and starts to see the return of some reflexes below the level of injury due to the hypersensitivity of the reflex muscle following denervation.
Phases 3 and 4 are the hyperreflexia phase. This occurs because the interneurons and lower motor neurons below the level of injury begin to sprout and attempt to re-establish synapses.
Autonomic problems also occur in spinal shock. A cervical lesion can cause the disappearance of arterial baroreceptor responses, thus bradycardia and hypotension could occur. Autonomic dysreflexia can also occur, characterized as hypertension, bradycardia, sweating (because of uncontrolled body temperature/poikilothermia), loss of bladder and bowel control, etc.
Vasomotor area
The vasomotor area in the medulla oblongata, together with the cardiovascular center and respiratory center, regulates blood pressure homeostasis. Excitatory inputs into the vasomotor area in the medulla oblongata include raised PCO2 (hypercapnia), low levels of O2 (hypoxia), pain, and carotid chemoreceptors. Aortic baroreceptors are located in the aortic arch. The aortic baroreceptor fibres merge with the vagus nerve and ascend to the nucleus of the tractus solitarius at the brainstem.
Nerve fibres
Nerve fibers are classified into three categories based on their diameter and conduction velocity. Each group has particular electrical characteristics and functions. Group A and B nerve fibers are myelinated, while group C nerve fibers are unmyelinated. Group B nerve fibers are most susceptible to hypoxia. Group A nerve fibers are most sensitive to pressure block, while group B and C nerve fibers are most susceptible to local anesthetics.
Proprioceptive (Aα) fibres have the largest diameters (13–20 μm) followed by cutaneous mechanoreceptor (Aβ) fibres (6–12 μm). Dorsal root C fibres have the smallest diameters (0.2–1.5 μm).
