Physiology Facts from Previous Papers

         Two types of NO synthase (NOS) have been identified: constitutive Ca2+- calmodulin dependent enzyme, and inducible Ca2+ - independent enzyme. Both enzymes are flavoproteins containing bound flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD).

·         Cells of JEJUNUM resemble that of PCT of Kidney.

Neurophysiology

·         The response of rod cells to light causes hyperpolarization, whereas olfactory stimuli result in depolarization.

The olfactory epithelium and rod cells are two examples of signal transduction that bypass a protein kinase system.

In the case of the olfactory epithelium, an odorant molecule binds to an odor-specific transmembrane receptor found on the modified cilia at the apical surface. The binding activates an odorant-specific G protein (Golf), which binds GTP. The resulting dissociation of the alpha subunit stimulates adenylate cyclase to produce cyclic AMP. Cyclic AMP directly stimulates the opening of the cation channels on the membrane of the bipolar olfactory receptor cells, leading to Na+ influx. The resulting change in membrane potential (depolarization) is transmitted from the modified cilia to the olfactory vesicle through the neuron to the basal axon. Axonal processes traverse the lamina propria as the olfactory nerve and pass through the cribriform plate of the ethmoid to terminate in the olfactory bulb. In the case of the rod, the cyclic nucleotide involved is cGMP.

Visual transduction involves closing of the Na+ channel in rod cells in response to photons of light. Rhodopsin is the visual pigment of rod cells and is composed of retinal, a vitamin A derivative, bound to opsins. Photons reaching rhodopsin isomerize retinal to the all-trans form from 11-cis retinal. The result is bleaching, which represents the dissociation of retinal from the opsins. The bleaching process results in a fall in cGMP within the cytosol. Transducin is a G protein that couples bleaching to cGMP through the action of a phosphodiesterase enzyme that cleaves cGMP to GMP. The closing of the Na+ channel results in a reduction in permeability to sodium ions and hyperpolarization of the cell membrane. The signal spreads to the inner segment and through gap junctions to nearby photoreceptor cells. In the presence of cGMP, the Na+ channel remains open; in its absence, the channel closes and the cell hyperpolarizes. Therefore, the rods and cones differ from other receptors in that hyperpolarization of the cell membranes occurs rather than the depolarization that occurs in other neural systems. Closing the channel slows down the release of the visual transmitter.

·         The anatomic arrangement allows frequency analysis of sounds:

1.       The basilar membrane responds to high frequencies at its base and to low frequencies at its apex.

2.       The hair cells in the base of the cochlear duct have short and fat stereocilia, which are stimulated by high frequencies.

3.       The hair cells in the apex of the cochlea have long and thin stereocilia, which respond best to low frequencies.

·         POSTURES:

·      Decorticate posture → upper extremities flexed, lower extremities extended ( CAR )

Decorticate posturing most often occurs in comatose patients with lesions below the thalamus but above the red nucleus.

·      Decerebrate posture → full extention of ALL extremities ( SCOOTER )

Comatose patients with lesions below the red nucleus but above the vestibular nucleus may have decerebrate posturing.

·         High-frequency sounds produce a vibration of the basilar membrane at the base of the cochlea (near the oval and round windows); low-frequency sounds produce a vibration of the basilar membrane at the apex of the cochlea (near the helicotrema).

·         Audiologists refer amplification phenomenon of middle ear bones as impedance matching.

·         Even extensive lesions of the visual cortex will not affect the center of the visual field, which is conveyed to the cortex by nerve fibers projecting from the macula. This is called macula sparing.

·         The inner ear is divided into three chambers (scala vestibuli, scala media, and scala tympani).

The scala vestibuli is separated from the scala media by Reissner’s membrane; the scala media and the scala tympani are separated by the basilar membrane.

The stapes is attached to the membrane of the oval window, which separates the middle ear from the scala vestibuli.

The scala tympani is separated from the middle ear by the round window.

The organ of Corti sits on the basilar membrane.

The fluid within the scala vestibuli and scala tympani (perilymph) is similar to interstitial fluid; the fluid within the scala media (endolymph) resembles intracellular fluid in that it contains a high concentration of K+.

Vibration of the stapes causes the fluid within the scala tympani to vibrate, which in turn causes the basilar membrane to vibrate. Vibration of the basilar membrane causes the cilia to bend back and forth. Bending the stereocilia toward the kinocilium causes K+ channels on the hair cells to open; bending the stereocilia away from kinocilium causes K+ channels to close. Auditory hair cells are unusual because they are depolarized by the flow of K+ into the cell. K+ can flow into the hair cells because the endolymph surrounding the apical portions of the hair cells contains a high K+ concentration.

The basilar membrane is most stiff at the base of the cochlea (near the middle ear) and most compliant at the apex of the cochlea. High-frequency sounds cause a greater vibration of the stiff portion of the cochlea, and, therefore, the hair cells located near the base of the cochlea transmit information about high-frequency sounds to the auditory cortex. Similarly, low-frequency sounds are transmitted to the auditory cortex by the hair cells near the base of the cochlea, which are located on the more compliant portions of the basilar membrane.

·         Light is detected by the rods and cones contained in the retina of the eye. The retina contains five types of neurons: photoreceptors (rods and cones), bipolar cells, ganglion cells, horizontal cells, and amacrine cells. Light rays from distant objects are normally focused on the photoreceptors by the cornea and the relaxed lens. When objects are brought closer to the eye, they are kept focused on the retina by the accommodation reflex, which causes the refractive power of the lens to increase. The rods and cones contain a visual pigment, called rhodopsin, which absorbs light energy. Rhodopsin contains two components: opsin, which determines the wavelength of light absorbed by rhodopsin, and retinal, which undergoes isomerization by light.

The photoreceptors are unusual because they hyperpolarize when they are stimulated by light. When the rods and cones are not stimulated, they are depolarized by the flow of Na+ into the cell through Na+ channels held in the open state by cGMP. The photoisomerization of retinal from its 11-cis form to its all-trans form activates rhodopsin, which in turn activates a G protein called transducin. Activated transducin activates a cGMP esterase. Hydrolysis of cGMP causes Na+ channels on the rod and cone outer segments to close, which produces the membrane hyperpolarization.

The neurotransmitter keeps the bipolar cells and, therefore, the ganglion cells in a polarized and relatively quiescent state. Hyperpolarization of the photoreceptors stops the release of an inhibitory neurotransmitter, which in turn causes bipolar cells to depolarize. The bipolar cells stimulate ganglion cells, which in turn convey information about the light stimulus to the visual cortex. The ganglion cells are the only cells in the retina to produce an action potential. Their axons form the optic nerve.

·         The gate-control hypothesis of pain states that pain transmission is suppressed by innocious signals in thick myelinated afferents (group II), whereas the pain sensation is enhanced by signals in thin afferents. Inhibitory interneurons in the dorsal horn of the spinal cord perform the gate-control through a special type of presynaptic inhibition called primary afferent depolarization (PAD), and the receptors on the cell body of the secondary neuron is the gate.

·         The reticular activating system (RAS) transmits facilitatory signals to the thalamus. The thalamus excites the cortex, and the cortex then excites the thalamus in a reverberating circuit. Such a positive feedback loop is what wakes us up in the morning. During the day external stimuli and internal factors including inhibitory interneurons balance the different activity levels.

·         The 3 cone types are uniformly distributed in the retina except in the fovea. The fovea has no cyanolab cones and no rods.

·         Movements in the visual scenery are depicted as opposite movements on the retina. Convergent inputs from the two eyes result in depth perception (ie, stereopsis or stereoscopic vision). Stereopsis depends upon the medial longitudinal fasciculus and the corpus callosum. These structures co-ordinate the movements of the two eyes.

·         The medial geniculate nucleus and the inferior collicle can increase its tone selectivity by dampening other sound signals. This explains the cocktail party effect.

·         CBF is normally 55 FU in humans at rest. One Flow Unit (FU) is one ml of blood per min per 100 g of brain tissue. This resting CBF and the oxygen uptake of the brain can double during cerebral activity and triple in active brain regions during an epileptic attack. Brain vessels are metabolically regulated. Increased PaCO2, and reduced PaO2 dilatate brain vessels and increase CBF. 

·         POMC peptides are neuroregulatory hormones: ACTH, endogenous opiates, b-endorphin,  b-lipoprotein, a-MSH and b-MSH.

·         CSF differs from blood in having a lower concentration of K+, glucose, and protein and a higher concentration of Na+ and Cl-; CSF normally lacks blood cells.

·         Many ganglion cells in primates can be classified as P, M, or W cells. P cells with small receptive fields and tonic and linear responses signal fine detail and wavelength. M cells have nonlinear responses and signal motion. Most W cells are difficult to activate.

·         The upper layers of the superior colliculus are involved in visual processing. The deep layers produce eye movements directed at visual targets that move into the field of vision or that are sources of somatosensory or auditory stimuli.

·         Sound waves are combinations of pure tones, and the composition of a sound can be determined by Fourier analysis. A pure tone is characterized in terms of its amplitude, frequency, and phase.

·         Specific thalamocortical afferent fibers terminate mainly in the middle layers of the neoocortex; diffuse thalamocortical afferent fibers synapse in layers I and VI.

Cortical efferent fibers from layers II and III project to other areas of the cortex; those from layer V project to many subcortical targets, including the spinal cord, brainstem, and striatum, as well as to non-specific thalamic nuclei; and layer VI distributes to the appropriate specific thalamic nucleus.

·         The cortical structure varies in different regions. Agranular cortex is found in the motor areas, whereas granular cortex (koniocortex) occurs in the primary sensory receiving areas. Homotypical cortex is found elsewhere in the neocortex.

Reproductive Physiology

·         Growth of the glandular elements of the breast is stimulated by progesterone; growth of the ductal elements is stimulated by estrogen.

·         Androgens, particularly dihydrotestosterone, are essential for regulation of the external genitalia in males. The fetus develops with multipotential internal and external genitalia. The development of male internal genitalia depends upon the presence of two hormones produced by the fetal testis—progesterone and Müllerian-inhibiting substance. The former stimulates growth and development of Wolffian ducts; the latter stimulates Müllerian duct regression.

·         Following insulin binding on muscle and adipocytes, the glucose transporter GLUT-4 is translocated to the cell membrane where it promotes glucose uptake by facilitated diffusion. GLUT-1 transporters are found virtually everywhere, as are GLUT-3 transporters. GLUT-2 transporters are found in liver, kidney, and intestinal cells. GLUT-5 transporters promote glucose absorption from the jejunum.

·         Cortisol is defined as a glucocorticoid because it promotes the conversion of amino acids to glucose (gluconeogenesis). It also decreases glucose uptake by muscle and adipocytes by decreasing the sensitivity of the cells to insulin. The net result is to provide more glucose to non-insulin-requiring cells.

·         Sperm contains chemicals that prevent sperm capacitation, thereby prolonging the viability of the sperm. In addition, the high potassium content of the secretion inhibits sperm motility, further adding to the viability. Sperm is secreted primarily by the seminiferous tubules and the alkaline nature of the secretion buffers the acidity of the vagina.

·         In nonpregnant women, the secretion of prolactin is kept tonically suppressed by secretion of dopamine from the hypothalamus. Prolactin is the main hormone of lactation. Hormone levels increase early in pregnancy due to the influence of estrogens. However, lactation does not occur early in pregnancy because estrogens and progesterone inhibit the interaction of prolactin with receptors located on the alveolar cell membranes. At term, estrogen and progesterone levels decrease and milk production begins usually within three days of delivery.

·         Glucagon secretion from pancreatic alpha cells is increased by increased plasma arginine levels

·         Q: child with deficiency of PROSTATE Gland – cause: def of 5 alpha reductase, so no DHT and no development of urogenital sinus.

·         Pituitary is NONDISCRIMINATING for testosterone, while Sertoli Cells are DISCRIMINAITNG for Testosterone i.e. it accepts testosterone from Leydig Cells only. ( remember ANABOLIC STEROID decreases Spermatogenesis)

·         HCG drives production of TESTOSTERONE in MALE FETUS, which need almost equal amount of Testosterone as an adult.

·         ESTROGEN is MITOTIC HORMONE needed to be formed from Testosterone in SERTOLI CELL for SPERMATOGENESIS.

·         LIBIDO:  

1.   testo / LH ratio

2         HTN,DM

3         Stress decreases

4         Partners

·         ERECTION: parasym

EMMISSION: symp

EJACULATION: symp & somatic motor

·         Leydig = Theca & Sertoli = Granulosa

·          

·         Remember, MENSTRUATION is part of FOLLICULAR phase & OVULATION is part of LUTEAL Phase.

·         Placental HCG keeps Corpus Luteum survive to produce Progesterone.

·         HPL is Growth Hormone of Placenta which also raises level of Blood Sugar and responsible for GESTATIONAL DIABETES.

·         Estrogen inhibits PIF so increases PROLACTIN Synthesis, but the same time it blocks PROLACTIN RECEPTORS, so MILK synthesis does not take place.

·         What initiates PARTURATION is decent of the head (releases PG & Oxytocin). Remember that OXYTOCIN continues PARTURATION, not INITIATE it.

·         Milk Synthesis starts just after PLACENTA is delivered as ESTROGEN level falls.

Milk Ejection starts by NIPPLE STIMULATION. Remember OXYTOCIN continues it, not initiates it.

Endocrine Physiology

·         In the world of Hormone, GH is like Hermaphrodite.

In the world of Hormone, Thyroxine is the Foundation Hormone, having permissive action on all other Hormones to act.

·         Androgen decreases Binding protein of lipid hormone, whereas Estrogen increases it.

·         Glucagon & Cortisol has permissive relationship for action.

·         Catecolamine & Cortisol has  also permissive relationship for action.

·         Catecolamine & Thyroid has  also permissive relationship for action.

·         All Releasing Hormones: from ARCUARE & VM Nucleus BUT GnRH from PREOPTIC NUCLEUS

·         Nonpulsatile: TRH, TSH

Pulsatile: others

·         Zona Glomerulaosa is not under control of ACTH, but under Angiotensin & K+. Damage to it is an Endocrine Emergency.

·         Desmolase is activated by ACTH, AT II & K+.

·         In 21-OH def: AT II increases

In 17-OH def & 11-OH def: AT II decreases

·         In 17-OH def & 11-OH def: increase BP is due to 11-DEOXYCORTICOSTERONE and not ALDOSTERONE

·         Cortisol activates: Pyruvate Carboxylase (makes OAA) & PEPCK (makes PEP) INSULIN INHIBITS BOTH.

·         Cortisol promotes GLYCOGENOLYSIS in MUSCLE, but it promotes GLYCOGEN SYNTHESIS in LIVER.

·         CRH from Hypothalamus causes release of POMC from Ant Pitutary.

POMC: 1. ACTH

               2. beta lipoprotein-> beta MSH & Endorphin

Alpha MSH is subunit of ACTH.

·         ALDOSTERONE saves Na+ by creating concentration gradient.

ALDOSTERONE loses K+ & H+ by creating electrical gradient.

·         There is NO EDEMA in PRIMARY Hypo/Hyper ALDOSTERONISM.

·         EDEMA is present in SECONDARY HyperALDOSTERONISM.

·         In Space/Weightlessness: decrease ALDOSTERONE, ADH & increase ANP = increase URINE FLOW

·         Target cells of GLUCAGON are on the LIVER & the LIVER & the LIVER. (not muscle & adipose)

·         Remember Amino Acid causes increase in both GLUCAGON  & INSULIN.

·         GH has both Catabolic & Anabolic (increase uptake of AA like insulin) Action.

·         EPINEPHRiNE promotes CORI’s Cycle. (Glycogen-Lactate-Glucose) (anarebic)

·         EPINEPHRINE does not breakdown aminoacid.

·         Ca x PO4 > Solubility Product = Bone deposition

Ca x PO4 < Solubility Product = Bone resorption

·         Both deficiency & excess of VITAMIN D leads to bone loss.

·         Activity of Thyroid hormone depends on:

4.       Presence of 3 iodines

5.       5’ position must be empty

·         Hypothyroid Patient have RESTING BRADYCARDIA, but remember that thet may present eith Tachycardia due to the episode of Hypoglycemia.

·         GOITER is euthyroid Until Proved Otherwise.

·         The release of TSH from pituitary depends on T4 in blood (not on blood T3) & level of T3 in Pitutary. That’s why inspite of being Euthyroid Goiter patient, their gland continues to enlarge as they have less T4. (T3 remains normal)

·          

·         Because it lacks 3 beta-hydroxysteroid dehydrogenase, the enzyme that converts pregnenolone to progesterone (the initial step in both glucocorticoid and mineralocorticoid synthesis), the fetal cortex synthesizes primarily dehydroepiandrosterone.

·         Prolactin is the main hormone of lactation. Hormone levels increase early in pregnancy due to the influence of estrogens. However, lactation does not occur early in pregnancy because estrogens and progesterone inhibit the interaction of prolactin with receptors located on the alveolar cell membranes. At term, estrogen and progesterone levels decrease and milk production begins usually within three days of delivery.

·         Calcium deficiency evokes a synergistic sequence that increases PTH and 1,25-(OH)2-D secretion. The combined actions of these two hormones increase the inflow of calcium and restore plasma concentrations to normal. They simultaneously dispose of the inflow of extra phosphate by enhancing its renal excretion.

In contrast, phosphate deprivation evokes a synergistic sequence that increases 1,25-(OH)2-D secretion, but reduces PTH secretion. The result is to restore the plasma phosphate concentration toward normal while disposing of the inflow of extra calcium by increasing its renal excretion.

·         FSH acts directly on the Sertoli cells of the seminiferous tubules to initiate mitotic and meiotic activity of germ cells. LH effects are thought to be mediated via stimulation of testosterone secretion by the Leydig cells.

·         Because fetal cortex lacks 3β- hydroxysteroid dehydrogenase, the enzyme that converts pregnenolone to progesterone (the initial step in both glucocorticoid and mineralocorticoid synthesis), the fetal cortex synthesizes primarily dehydroepiandrosterone.

·         GH hormone exerts a wide variety of effects on body metabolism, including increased protein synthesis, decreased use of carbohydrate, and increased use of fat. The net effect is the accumulation of protein and conservation of carbohydrate at the expense of fat stores.

·         Synthesis and secretion of melatonin are increased in the dark via input from norepinephrine secreted by postganglionic sympathetic neurons. Melatonin is synthesized in the pineal gland from the amino acid tryptophan. Pinealomas (tumors of the pineal gland) that destroy the pineal gland and reduce secretion of melatonin and cause hypothalamic damage may cause precocious puberty by removing the inhibitory effect of melatonin on the pituitary response to gonadotropin-releasing hormone.

·         α-Glycerophosphate is produced in the course of normal use of glucose. In the absence of adequate quantities of a-glycerophosphate—a normal acceptor of free fatty acids in triglyceride synthesis—lipolysis will be the predominant process in adipose tissue. As a result, fatty acids will be released into the blood. The prevailing insulin level is decisive in the selection of substrate by a tissue for the production of energy. Insulin promotes use of carbohydrate, and a lack of the hormone causes use of fat mainly to the exclusion of uptake and use of glucose, except by brain tissue. Indirect depression of use of glucose by excess fatty acids is a result, and not a contributing cause, of increased use of fat.

Renal Physiology

·         Tf/P ratio = 1 means substance is freely filtered.

If less than 1, substance is not freely filtered.

·         In ACIDOSIS: K+ filtration: increase, Serum K+: decrease, K+excretion: increases

·          

·         The H+ produced is buffered mainly by the large amount of hemoglobin in the red blood cells. Bicarbonate is not an effective buffer of volatile acid.(CO2).

·         The major structural differences between epithelial cells of the proximal and distal tubules account for the fact that 65% of glomerular filtrate is reabsorbed in the proximal tubule and that the proximal tubule is more permeable to water.

The proximal tubule has an extensive brush border composed of numerous microvilli, which markedly increase the surface area for reabsorption, and the tubule also has an extensive network of intracellular channels.

The distal tubule has many more tight junctions between cells, which makes it less permeable to water. No significant difference in basement membrane thickness is observed between the proximal and distal tubules.

·         The macula densa senses the chloride concentration of the fluid flowing from the ascending limb of Henle's loop into the distal convoluted tubule.

An increase in NaCl concentration occurs when the amount of fluid flowing through the ascending limb increases because there is less time available for the reabsorption of NaCl. The resulting increase in Cl– concentration results in the release of adenosine from the macula densa.

Adenosine constricts the afferent arteriole resulting in a decrease in filtration and a return of the flow rate within the nephron toward normal. This response is referred to as tubuloglomerular feedback.

·         Persistent diarrhea will result in a metabolic acidosis, due to the loss of the bicarbonate-rich secretions from the pancreas and gallbladder. The ensuing metabolic acidosis will decrease the plasma concentration of HCO3–, decreasing the amount of bicarbonate that is filtered into the proximal tubule. At the same time, the metabolic acidosis will increase ammonia production by the proximal tubule as well as H+ secretion and production of new bicarbonate by the distal nephron. Because the metabolic acidosis is produced by the loss of bicarbonate, the anion gap will remain within normal limits.

·         The movement of K+ into cells is facilitated by the presence of insulin and epinephrine. During exercise, epinephrine hastens the movement of K+ into muscle cells, preventing the accumulation of K+ in the extracellular space around active muscle cells.

·         Free water clearance is the amount of water excreted in excess of that required to make the urine isotonic to plasma. It is calculated using the formula

 CH2O = V × [1 – (UNa + UK)/PNa]

Free water clearance is positive when the urine is dilute (more than a sufficient amount of water is excreted), and free water clearance is negative when the urine is concentrated (not enough water is excreted to make the urine isotonic to plasma).

·         Phosphate transporter is electrically neutral, requiring 2 Na+ molecules for every HPO42– molecule that it transports. The transporter is inhibited by parathyroid hormone (PTH).

·         Alkalosis dissociates protein molecules, which bind  ionised calcium. The hypocalcaemia opens Na+ - channels, and the influx increases the excitability of neuromuscular tissues, which releases tetanic cramps.

·         Primary hyperaldosteronism (Conn’s hypercorticism disease) and all types of secondary hyperaldosteronism also lead to hypernatraemia combined with hypokalaemia and enlarged blood volume. Cerebral failure and convulsions are alarming signs, but there are no specific symptoms and signs of hypernatraemia.( NO EDEMA)

·         Urinary buffers are necessary for effective excretion of acid, because the minimum pH of the urine is only 4.0 to 4.5. Phosphate is the primary urinary buffer.

·         Aldosterone secretion is increased when plasma concentrations of angiotensin II or potassium (K+) are increased.

·         Filtered Load = GFR / Px = 120 mL/min / 10 mg/mL = 12 mg/min

·         Excretion = Ux * V = 10 mg/mL * 1.5 mL/min = 15 mg/min

·         Secretion = 15 mg/min − 12 mg/min = 3 mg/min

·         The intracellular Na+ concentration of renal epithelial cells is pumped out of renal epithelial cells by Na-K pumps located on the basolateral surface of the epithelial cells. The Na/H exchanger and the Na-glucose transporter are located on the apical surface of the epithelial cells. Na+ is transported from the peritubular spaces to the capillaries by solvent drag.

·         The net glomerular capillary pressure (for Starling forces) is equal to the glomerular capillary pressure minus the sum of the plasma oncotic pressure and intrarenal pressure. Compression of the renal capsule increases the intrarenal pressure and therefore decreases the net capillary filtration pressure.

·         Net acid excretion = ([titratable acids] + [NH4+] − 2 [HCO3−]) × urine volume per day

·         When water is filtered across the glomerulus, the protein concentration (the oncotic pressure) within the capillaries increases, which in turn increases the efficiency by which water reabsorbed from the proximal tubule is returned to the circulatory system. If GFR increases, it results in a larger increase in oncotic pressure. This in turn increases the amount of water reabsorbed from the proximal tubule.

·         The distal nephron has a negative luminal potential because it is poorly permeable to negatively charged ions. Therefore, when Na+ is reabsorbed, negatively charged ions, primarily Cl−, lag behind, producing a negative intraluminal potential.

·         An increase in NaCl concentration occurs when the amount of fluid flowing through the ascending limb increases because there is less time available for the reabsorption of NaCl. The resulting increase in Cl− concentration results in the release of adenosine from the macula densa. Adenosine constricts the afferent arteriole resulting in a decrease in filtration and a return of the flow rate within the nephron toward normal. This response is referred to as tubuloglomerular feedback. If NaCl concentration decreases, for example, when circulating blood volume decreases, the decreased Cl− concentration results in the release of renin from granular cells of the juxtaglomerular apparatus.

·         Nitric oxide dilates the afferent arteriole and constricts the efferent arteriole, producing a rise in glomerular capillary pressure (and glomerular filtration) without having much of an effect on renal blood flow.

·         Prostaglandins, bradykinin, and dopamine all increase renal blood flow. Cyclooxygenase inhibitors, such as aspirin, that decrease prostaglandin synthesis may impair renal blood flow sufficiently to exacerbate the effects of renal failure.

·         Phosphate is almost completely reabsorbed in the proximal tubule, so its concentration decreases along the length of the tubule.

·         ANP increases Na+ excretion by decreasing the amount of Na+ reabsorbed from the inner medullary collecting duct by decreasing the permeability of the apical membrane of the collecting duct epithelial cells. Less Na+ is able to enter the epithelial cells and therefore, less Na is reabsorbed. ANP also increases Na+ excretion by increasing the filtered load of Na+.

·         The proximal tubule reabsorbs approximately two-thirds of the filtered water and two-thirds of the filtered Na+, Cl–, and K+. Therefore, the concentration of these substances is the same at the beginning and end of the proximal tubule. Because creatinine is not reabsorbed, its concentration increases from the proximal to distal ends of the proximal tubule. Phosphate, however, is almost completely reabsorbed in the proximal tubule, so its concentration decreases along the length of the tubule.

Respiratory Physiology

·         Salt water increases COMPLIANCE by decreasing ST. so lung floats. Whereas fresh clean water, lungs sink.

·         SURFACTANT:

1.       Lowers ST

2.       Promotes stability among different sized alveoli

3.       Reduces capillary filtration forces

·         FUNDA: Hyperventilation: Respi Alkalosis

        HyperRespiration: Respi Acidosis (as Rapid & Shallow breathing, only conducting zone exchanged)

·         The Gas least expected to be in CONDUCTING ZONE at the END OF INSPIRATION is CO2.

·         Rate is to CO2 as the DEPTH is to O2.

·         Emphysema has more COMPLIANCE but less ELASTICITY.

·         Compliance is inverse to Elasticity.

Compliance is inverse to Recoil. Recoil is determined by ST & Laplace law.

·         During inspiration, the greatest airflow to alveoli is at: MID-INSPIRATION

·         In pneumothorax, interpleural pressure becomes more positive.

·         Alveolar pressure at the beginning of Insp: 0

Alveolar pressure at the end of Insp: 0

·         During EXERCISE, PACO2 remains normal, what increases is the PVCO2.

·         PACO2 = metabolism / alveolar ventilation

·         PAO2 depends on Patm & FiO2.

·         PiO2 = (Patm-47) x FiO2

So PAO2 = PiO2 – PACO2

·         Solubility in Blood: CO > CO2 > O2

Affinity to Hb: CO > O2 > CO2

·         P50 is when Hb is 50% saturated 50% with O2. At that point PO2 is around 26 mmHg.

·         Chloride Shift: occurs at TISSUES. to maintain electrical neutrality as HCO3 moves out of RBCs, Cl moves in. its imp for CO2 transport. Cl influx into RBCs.

·         Reverse Chloride Shift: at LUNGs. Cl efflux into RBCs.

·         Even after ACCLIMATIZATION at high altitude, remember that you still Hyperventilate and your Peripheral Receptor remains stimulated because PO2 is not changed yet. Even your Hb saturation remains decreased. Your Hb conc will increase.

·         Normal (A-a) difference: 0-10 (age x 0.4)

·          

·         ­AVO₂ Difference

Tissue will extract more O₂ d/t lack of RBC and Hb available → Therefore, patient will not appear SOB

• Heart has highest AVO₂ difference at rest onlyà will extract the most O₂
• Muscle will have the highest AVO₂ after exercise
• GI will have the highest AVO₂ after a meal
• Kidney has the lowest AVO₂ all the time.

·         Tidal Volume = 10 – 15 cc/kg

·         The physiological dead space can be calculated using the Bohr equation:

VD = VT · [PaCo2 – PeCo2] ÷ PaCo2

·         Compliance = ΔV/ΔP

·         Flow is matched at the middle of the lung.

·         V/Q is greater at the top overall because flow is less at the top.

·         V/Q is greater at the bottom ONLY with inspiration.

·         Every V/Q mismatch presents with restrictive pattern.

·         A:a gradient (Alveoli:arteriole)

If ↑ = A > a = restrictive

If ↓ = A < a = Hb picking up too much O₂

·         Afferent (CN IX) and Efferent (CN X) for carotid body

Afferent and Efferent are both CN X for Aortic body.

·         A diffusion-limited (CO & O2) transport process is one in which the alveolar gas does not reach equilibrium with the end-pulmonary capillary blood. Carbon monoxide (CO) is transported by a diffusion-limited process because it is avidly bound to hemoglobin. So much CO binds to hemoglobin that the partial pressure of CO in the capillary blood remains near zero. As a result, the concentration gradient from alveolar gas to capillary blood remains constant and the amount of CO diffusing across the alveolar capillary interface depends only on the permeability of the gas.

In contrast, all of the other gases reach equilibrium with the capillary blood, and, therefore, the amount of those gases that diffuses across the alveolar capillary membrane is dependent on the amount of blood passing through the pulmonary capillaries. This type of transport process is described as perfusion-limited (O2, CO2, N2O).

·         Diffusing Capacity is the volume of gas transported across the lung per minute per mmHg partial pressure difference.

 It is determined by the surface area and the thickness of the alveolar-capillary interface.

Increases in the diffusing capacity can be produced by opening pulmonary capillaries, expanding the surface area of the pulmonary capillaries, optimizing the V/Q ratio within the lung, or by increasing the concentration of hemoglobin within the blood (polycythemia).

It can be decreased by mismatching of ventilation and perfusion, pulmonary edema, or pulmonary emboli, all of which interfere with gas diffusion.

·         The pulmonary transfer of O2 and CO2  is perfusion-limited over a wide range of activity levels.

·         The tissue transfer of O2 and CO2  is diffusion-limited over a wide range of activity levels.

·         The standard affinity of the haemoglobin-CO reaction is 250 times greater than that of haemoglobin-O2 .

·         The single-breath CO diffusing capacity (transfer factor) is normally 3 ml STPD s-1 kPa-1 at rest and 7.5 during maximal exercise.

·         There are four mechanisms of hypoxemia: anatomical shunt, physiological shunt, [Vdot]/[Qdot] mismatching, and hypoventilation.

There are two mechanisms of hypercarbia: increase in dead space and hypoventilation.

A change in cardiac output is the only nonrespiratory factor that affects gas exchange.

·         Three cell types produce mucus: surface secretory cells, tracheobronchial glands and Clara cells.

·         At high altitudes, the atmospheric pressure is decreased; however, the percentage of O2 in the atmosphere remains the same. Hypoxemia stimulates peripheral chemoreceptors causing respiratory alkalosis, which shifts the OBC to the left. However, alkalosis activates phosphofructokinase in glycolysis causing increased production of 1,3-BPG, which is converted to 2,3-BPG. This brings the OBC back to normal or slightly to the right, leading to increased release of O2 to tissue.

·         PaCO2 is inversely proportional to alveolar ventilation: PaCO2 ∝ 1/VA

If the patient in the question doubles his tidal volume, his alveolar ventilation (VT − VD) will increase from 3 L/min (see question 209) to [(800 mL − 100 mL) и 10 breaths/min] = 7 L/min

Therefore, his PaCO2 will decrease from 50 mmHg to 21 mmHg:

PaCO2 и VA = constant

50 mmHg и 3 L/min = PaCO2 и 7 L/min

PaCO2 = 21 mmHg

·         V/Q mismatches will cause arterial oxygen levels (PaO2) to decrease. Decreased PaO2 will stimulate the peripheral chemoreceptors, which, in turn, will increase alveolar ventilation and decrease PaCO2. The decreased PaCO2 will cause a respiratory alkalosis (increasing pH). Hypoxemia will also cause lactate levels to rise, increasing the anion gap (and blunting the rise in pH). The fall in PaO2 causes the A-a gradient to rise.

·         The physiological dead space can be calculated using the Bohr equation: VD = VT и [PaCO2 − PeCO2] ÷ PaCO2

·         The modified alveolar gas equation is: PaO2 = PiO2 − (PaCO2 /R)

·         In the tissues, the diffusing capacity is the volume of gas transported across the lung per minute per mmHg partial pressure difference. It is determined by the surface area and the thickness of the alveolar-capillary interface. Increases in the diffusing capacity can be produced by opening pulmonary capillaries, expanding the surface area of the pulmonary capillaries, optimizing the V/Q ratio within the lung, or by increasing the concentration of hemoglobin within the blood (polycythemia). It can be decreased by mismatching of ventilation and perfusion, pulmonary edema, or pulmonary emboli, all of which interfere with gas diffusion.

·         The forces tending to remove fluid from the alveoli are the negative interstitial fluid pressure and the osmotic pressure exerted at the alveolar membrane by ions and crystalloid molecules in the interstitial fluid. Fluid movement into pulmonary capillaries, however, is a function of plasma oncotic pressure.

·         The central chemoreceptors are located at or near the ventral surface of the medulla. They are stimulated to increase ventilation by a decrease in the pH of their extracellular fluid (ECF).

·         The pulmonary capillaries are more permeable to proteins than the skeletal muscle capillaries, and, therefore, the interstitial concentration of protein is greater in the pulmonary circulation.

·         Hyperventilation occurs when the rate of alveolar ventilation reduces the arterial PCO2 below 40 mmHg. Pregnancy produces hyperventilation because progesterone stimulates the brain stem respiratory centers to increase alveolar ventilation above that required to maintain arterial PCO2 at 40 mmHg.

·         During exercise, ventilation increases in parallel with carbon dioxide production so that the arterial PCO2 remains at 40 mmHg. Metabolic alkalosis causes a small decrease in alveolar ventilation, producing a compensatory respiratory acidosis.

·         The respiratory alkalosis will cause Ca2+ to bind to plasma proteins, lowering the concentration of ionized Ca2+.

·         Most of the airway is within the thoracic cavity, and, therefore, the intrathoracic pressure affects airway diameter and resistance. The intrathoracic pressure is most negative at the total lung capacity. The negative thoracic pressure increases airway diameter and decreases airway resistance.