Human Physiology Exam 4

Vasopressin

(aka Arginine Vasopressin/AVP; Antidiuretic Hormone/ADH) directly regulates the permeability of the distal tubule and collecting duct to water by promoting the retention of water. Vasopressin is produced and secreted in the hypothalamus. Then, packaged into vesicles and trafficked into posterior pituitary gland. AVP is released into veins and into blood stream. Without vasopressin, the collecting duct is relatively impermeable to water, so the urine will have a low osmolarity (dilute). With maximal vasopressin, the collecting duct is freely permeable to water, so the urine will have a high osmolarity (concentrated).

Brain Natriuretic Peptide (BNP)

Made by ventricular myocardial cells. Production of BNP increases with ventricular dilation and increased ventricular pressure so important indicator of heart failure.

Changes in osmolarity with decreases in total body water volume

1) Decreased volume, increased osmolarity occurs due to pathological disturbance caused by emergency situation (ex. dehydration and/or diarrhea). Results in lot of fluid loss and cell shrinkage because increased osmolarity. Response: Minimize H2O loss. 2) Decreased volume, no change in osmolarity. Occurs with hemorrhage. Blood loss is loss of isosmotic fluid from ECF. Kidneys can't restore lost volume. Blood transfusion or isotonic saline needed. 3) Decreased volume, decreased osmolarity. Caused by incomplete compensation of dehydration but very uncommon. Try to minimize H2O loss.

Changes in osmolarity with increases in total body water volume

1) Increased volume, increased osmolarity. Can occur when someone drinks a lot of liquids and eat a lot of salty foods. Results in increased ECF volume and osmolarity. Response: excretion of hypertonic urine. 2) Increased volume, no change in osmolarity. Ingestion of isotonic saline results in excretion of isotonic urine where volume excreted equals volume ingested. 3) Increased volume, decreased osmolarity. Occurs when drinking pure water without ingesting solutes. Ideal goal: excrete pure water to conserve solutes. Reality: solutes are always lost in urine so compensation is imperfect in this case and hypotonic urine is excreted.

Kidney Regulation of pH

1) Reabsorption of filtered HCO3- in the proximal tubule. 2) De novo HCO3- synthesis/H+ secretion into the proximal and distal nephron.

Gastrointestinal Motility

3 General Patterns of Muscle Contraction: 1) Migrating motor complex: housekeeping contractions between meals. No active transport of bolus, moves residual food particles/bacteria through system (ex. Stomach rumbling) 2) Peristalsis: propulsion of bolus by contracting behind bolus. 3) Segmental Contractions: mixing of bolus by alternate contraction and relazation in intestine.

Secretion in GI Tract

7 liters of fluid is secreted into the GI tract. 50% from salivary glands, pancreas, liver and 50% from epithelial cells. Mostly ions (Na+, K+, Cl-, HCO3- and H+) secreted first and water follows. So generating isotonic saline in the lumen. Facilitates digestion and absorption of nutrients.

Acid Base Balance

Acidosis: process that adds H+ to the body fluids. Results in low pH and neurons become less excitable (CNS depression). Alkalosis: process that removes H+ from the body fluids (or adds OH-). Results in high pH and neurons are hyper excitable. The primary cause (acidosis or alkalosis) of alkalemia or acidemia can be determined from measurements of arterial blood gases and pH. Acid-base disturbances may be incompletely compensated. Renal and respiratory compensation can move pH closer to normal but may not correct the problem.

ECF Osmolarity

Affects cell volume. If ECF osmolarity is high, water will move out of the cell and cell will shrink. If ECF osmolarity is low, water moves into the cell and the cell swells.

Protein Absorption

Amino acids have own transporters. Oligopeptides versus di and tri peptides. Most amino acids are carried by sodium dependent cotransport proteins. oligopeptides transported using an H+ transporter.

Angiotensin II

Angiotensin II increases blood pressure through four main pathways: Increases vasopressin secretion by ANG II receptors in the hypothalamus. Vasopressin helps conserve blood volume and blood pressure. Stimulates thirst via hypothalamus which also increases blood volume and blood pressure. Is a vasoconstrictor which causes increase in blood pressure. Activation of ANG II receptors in cardiovascular system increases sympathetic output in heart and blood. Directly acts on adrenal cortex to increase sodium reabsorption to increase volume and maintain osmolarity.

Juxtamedullary nephrons

Have long loops of henle that descend deep into the medulla. This helps drive reabsorption.

Vasopressin and Aquaporins

Aquaporins regulate movement of water into and out of the distal nephron. AQP2 is the water channel regulated by vasopressin and is found on the apical membrane and in the membrane of cytoplasmic vesicles. Vasopressin binds to membrane receptor on basolateral membrane which activates cAMP second messenger system. This causes vesicles to fuse with apical membrane and insert AQP2 into membrane. Increases permeability of collecting duct cell so water moves into cell and into blood by osmosis.

Intestinal Phase

Begins in the duodenum. The intestinal phase involves neural and endocrine feedback between the small intestine, pancreas, and stomach. Release of chyme into small intestine which induces enteric nervous system to stop secretion of acid, pepsin, and lipase. This shuts down gastric phase. Chyme is very acidic and it induces secretin release which decreases motility and inhibits acid secretion which stops gastric phase.

Changes in osmolarity without changes in total body water volume

Body fluid osmolarity may change independently of total body water volume. 1) No change in volume, increased osmolarity. Occurs when ingesting salt with no water. Results in increased ECF osmolarity. Response: intense thirst and highly concentrated urine with little volume to conserve water. 2) No change in volume, decreased osmolarity. Occurs when dehydrated person replaces lost fluid with pure water. Volume becomes constant. Response: Hypotonic urine. Can also drink electrolyte beverages to restore salt.

Carbohydrate Absorption

Carbohydrates are only absorbed as glucose, fructose, or galactose. Occurs in small intestine. Transported across intestinal mucosa with cotransport w sodium. Glucose/galactose enters cell through SGLT and leaves through GLUT2 into bloodstream. Fructose enters cell through GLUT5 and leaves through GLUT2.

Carbohydrate Digestion

Carbohydrates must be digested into one of 3 monosaccharides before being absorbed. Amylase breaks down polymers into disaccharides in the mouth. Then these get broken down into monosaccharides. Example: glycogen broken into maltose, sucrose, lactose (disaccharides). These get broken down into monosaccharides such as glucose, fructose, and galactose.

Compensatory respiratory alkalosis

Changes in plasma pH directly affect ventilation rate to compensate for a pH derangement. An increase in H+ causes an increase in CO2 because equation shifts. High H+ sensed by carotid and aortic receptors and high CO2 sensed by central receptors. Both receptors transmit signal to respiratory control centers in the medulla which causes ventilation muscles to contract more and increase rate/depth of breathing. This causes pCO2 to decrease which causes H+ to decrease.

GI Contractions

Contractions can be phasic or tonic. Phasic contractions have contraction-relaxation cycles that only last a few seconds and occur in the anterior portion of the stomach and in sphincters. Tonic contractions are sustained for minutes or hours and occur in the posterior region of the stomach and in the small intestine. Slow wave potentials - originate in interstitial cells of Cajal (ICCs) and are graded potentials that summate over time to help smooth muscles contract. ICCs function like pacemaker cells and coordinate GI motility. Slow waves that begin in ICCs spread through gap junctions. Link between ICcs and bowel disorders such as IBS.

Countercurrent Multiplier

Contributes to formation of the renal medullary concentration gradient. Very close loops which allows for efficient transfer. Loop of Henle flows in opposite direction to the vasa recta (peritubular capillaries). Net result is to produce hyper osmotic interstitial fluid in the medulla and hyposmotic filtrate laving the loop of henle. As filtrate is coming into loop, interstitial fluid outside has a higher osmolarity. This causes movement of water out of the descending limb until isosmotic. Active transport of solutes out of the ascending limb dilutes the filtrate and increases osmolarity of the interstitial fluid. Vasa recta picks up water from descending limb and picks up solutes from ascending limb. This prevents the water from diluting the concentrated medullary interstitial fluid. Countercurrent exchange in the Vasa Recta preserves medullary osmolarity

Vasa Recta

Countercurrent exchange in the Vasa Recta preserves medullary osmolarity. Losing water to interstitial fluid. On another side, water from descending loop of Henle is being absorbed

Digestive System Processes

Digestion: chemical and mechanical reduction of macromolecules into smaller transportable units. Absorption: transfer of molecules from GI lumen to ECF/bloodstream. May be active or passive Motility: movement of material through the GI tract. Secretion: water, ions, enzymes move from cells into lumen or bloodstream.

ACE Inhibitors

Example: lisinopril, enalapril, captopril Blocking ACE prevents conversion of ANG I to ANG II. ANG II is a potent vasoconstrictor. Therefore, blocking ACE leads to vasodilation and a decrease in blood pressure. Less ANG II also means less aldosterone release, a decrease in sodium reabsorption, so a decrease in ECF volume. These all lower blood pressure. ACE also breaks down bradykinin (a cytokine). So Blocking ACE increases bradykinin levels causing further vasodilation. Clinically, ACE inhibitors are often combined with diuretics to enhance their effectiveness

Potassium Balance

Extracellular K+ concentration is tightly regulated. Normal levels: 3.5-5 mM K+ in plasma. Hypokalemia: low blood potassium concentrations Hyperkalemia: high blood potassium concentrations Aldosterone helps maintain potassium levels. If plasma K+ is too high, aldosterone released into blood. Changes in K+ concentration affect resting membrane potential of all cells. If plasma/ECF K+ concentration decreases, more K+ leaves the cell and the resting membrane potential becomes more negative. This causes muscle weakness because it is more difficult to fire action potentials. If ECF K+ increases, cell becomes depolarized. So easier to fire an action potential because closer to threshold.

Layers of GI Tract Wall

Four layers: Mucosa - tiny villi that increase surface area to help absorb nutrients, innermost layer Submucosa - blood supplies, lymphatic vessels Muscularis externa - motility, contraction and movement of GI tract Serosa - most external, basement membrane, holding everything together

Digestion Phases

Has three phases. 1) Cephalic Begins when you see, smell or taste food. Involves the brain, mouth, pharynx, and esophagus. Sensory input that signals to brain to start rounding up process of digestion Long reflexes that begin in the brain which activate feedforward responses. 2) Gastric Begins when the bolus enters the stomach. Involves the storage, digestion, and detoxification of food. First defense against infection. 3) Intestinal Begins when chyme enters small intestine. Involves the digestion, motility, and absorption of nutrients. The cephalic and gastric phases stimulate stomach secretions and motility (parasympathetic response)

Water Transfer (Volume Conservation)

Have to take in and excrete same amount of water to maintain a constant volume. Water conservation is regulated by the kidneys. Kidneys cannot restore lost volume; they can only conserve fluids. Average daily intake is 2 L and can only gain water through absorption in GI tract. (IV is medical exception). Water is lost through urine/feces mostly, but also breathing and sweating. Special situations of water loss: Excessive sweating/diarrhea.

Decrease in Total Water Volume

Homeostatic reflexes respond to changes in total body water volume. Decrease in total body water volume causes a decrease in blood volume and blood pressure. Volume receptors in atria and carotid and aortic baroreceptors sense change in volume and trigger homeostatic response. Cardiovascular system responds by increasing cardiac output and causes vasoconstriction to increase blood pressure. Increase water intake by changing behavior (Thirst). Kidneys will conserve water to minimize further loss.

Control of Aldosterone Secretion

Hypotension (indirectly) and hyperkalemia (directly) primarily control aldosterone secretion. Hyperkalemia (high blood potassium) acts directly on adrenal cortex. Hypotension acts indirectly through the renin-angiotensin-aldosterone system Less major: high ECF osmolarity acts on adrenal cells to inhibit aldosterone secretion during dehydration and extremely low plasma Na+ can cause aldosterone secretion.

Renin Secretion

Hypotension increases renin secretion from granular cells by three pathways which initiates the RAS pathway. 3 main ways that renin is produced: Decrease in blood pressure directly sensed by granular cells of afferent arteriole so they secrete renin. Decrease in BP related to Decrease in GFR. Decrease in NaCl transport sensed by macula densa which sends paracrine signals to granular cells in afferent arterioles to increase renin production. Decrease in BP monitored by Cardiovascular control center which increases sympathetic activity to secrete renin.

Response to Changes in H+

Immediate: pH buffers in the extracellular and intracellular fluids will prevent most of the changes in H+ concentration. Fast: The respiratory system can compensate by adding or removing carbonic acid from the body fluids. Respiratory system is second defense. Compensate for 75% of disruption within seconds/minutes Slow: The kidneys can compensate by excreting or reabsorbing additional H+. If first two don't properly correct pH, the kidneys secrete protons.

Dehydration Compensation

In severe dehydration, mechanisms aim to increase blood pressure, increase ECF volume, and decrease osmolarity. Four main mechanisms: cardiovascular, ANG II, vasopressin, and thirst. Net result: 1) Restoration of volume by water conservation and fluid intake 2) Increase in blood pressure by increased blood volume, increased cardiac output and vasoconstriction 3) Decrease osmolarity by decreased sodium reabsorption and increased water reabsorption.

Increase in Total Water Volume

Increase in total body water volume causes an increase in blood volume and blood pressure. Cardiovascular system responds by decreasing cardiac output and vasodilation to decrease blood pressure. The kidneys excrete water and salts which decreases the volume of ECF and ICF which also results in a decrease in blood pressure.

Horizontal Osmotic Gradient

Ion transporters in the tubular epithelium of the ascending limb create the horizontal gradient. Active transport of some solutes and passive diffusion of others down their gradients. Salts are reabsorbed into cells of ascending loop. Active transport causes higher osmolarity at base of the loop. A 200 mOsm/L gradient established at each horizontal level. Fluid flows. Continuous ascending limb pump and descending limb passive flow reestablish gradient at each horizontal level.

Enterocyte

Most nutrient absorption takes place in the small intestine. The large intestine absorbs remaining water and salts. One single villus in small intestine is made of many enterocytes (absorptive cells) which themselves have microvilli. AKA enormous surface area.

pH balance in the body (input/output)

Most of proton input ingested through the diet (lactic acid, fatty acid, etc.) Metabolism also results in H+ input. In severe anaerobic situation, overproduction of lactic acid results in lactic acidosis. Overproduction of ketoacids result in ketoacidosis. Biggest acid input is production of CO2 during respiration which results in more H+ because of bicarbonate reaction. Combat proton input by diet through ventilation, buffers, and directly secrete protons through renal system.

Hepatic Portal System

Most of the absorbed nutrients pass through the liver EXCEPT LIPIDS. System has two sets of capillary beds: one that picks up nutrients at intestine and another that delivers nutrients to liver. Liver serves as a filter that removes harmful substances before they enter the systemic circulation. Lipids (fats) enter lacteals and go through lymphatic system.

Anatomy and Mass Balance of Digestive System

Oral cavity, esophagus, stomach, small intestine, large intestine, rectum.

Vasopressin Release

Osmolarity and feedback from the heart and baroreceptors regulate vasopressin (AVP) release. Increased plasma osmolarity causes vasopressin release which causes increased water reabsorption and decreased plasma osmolarity. Plasma osmolarity is regulated by osmoreceptors (stretch sensitive neurons) in the hypothalamus. If plasma osmolarity is too high, osmoreceptors shrink and fire to stimulate vasopressin release. Decreased blood pressure sensed by carotid and aortic baroreceptors which signal sensory neurons in hypothalamus to release vasopressin. Decreased atrial stretch due to low blood volume sensed by atrial stretch receptor which also signals to sensory neurons in hypothalamus.

Atrial Natriuretic Peptide (ANP)

Peptide hormone produced in myocardial cells in atria. Cleaved into many active hormone fragments. Is released when increased blood volume causes increased atrial stretch. ANP increases sodium and water excretion which decreases blood volume and pressure.

GI Function

Primary function is to move nutrients, water, and salt from the external environment into the body's internal environment. Challenges: Secrete enzymes and break down food without breaking down organs. Matching fluid input with output. Keep out pathogens; 80% of lymphocytes are found in the small intestine.

Protein Digestion

Proteins must be digested into amino acids, di- or tri- peptides, or small proteins before absorption. Endopeptidases: Attack internal bonds Pepsin-secreted as pepsinogen by the stomach. Trypsin-secreted by the pancreas Chymotrypsin-secreted by the pancreas Exopeptidase: Attack external bonds Aminopeptidase - small intestine Carboxypeptidase- secreted by pancreas Acidic pH helps by denaturing proteins and breaking down hydrogen bonds and sulfuric bonds.

Regulating Sodium

Regulating Sodium Regulates Extracellular Fluid Volume. NaCl ingestion causes increase in osmolarity but no change in volume. This drives two effects: vasopressin and thirst. Both cause osmolarity to decrease. Vasopressin causes renal water absorption which has two side effects: ECF volume increase and bp increase. Kidneys and cardiovascular system respond to return these two to normal. Kidneys regulate most Na+ excretion and only renal Na+ absorption is controlled.

Diuresis

Removal of excess water in urine. (Low urine osmolarity).

Renal Medullary Gradient

Requires three things: 1) Countercurrent flows of blood and tubular fluid. 2) A transport system that establishes a horizontal osmotic gradient. 3) Different water permeabilities of the descending and ascending limb of the Loop of Henle.

Gastric Parietal Cells

Secrete HCl (acid) into lumen of the stomach which can create a pH of 1. Acid in stomach triggers release of pepsin and somatostatin. It also denatures proteins by breaking hydrogen and disulfide bonds and inactivates salivary amylase. Produces an "alkaline tide" - as acid is being secreted into lumen, bicarbonate is absorbed into blood which acts as a buffer and makes blood leaving stomach less acidic. Pathway for acid secretion: H+ pumped into lumen of stomach by H+/K+ ATPase. Cl- follows H+ out of the cell by moving through chloride channels so net result is HCl into lumen. Omeprazole is an inihibitor of the H+ K+ ATPase which can be used to combat over secretion of HCl.

Bile

Secreted and made by liver. Stored in gallbladder. Released into duodenum via common bile duct. Made up of bile salts, bile pigments, and cholesterol.

Pancreatic Enzyme Secretions

Stimulated by distension, presence of food in the intestine, neural signals, and CCK. Secretions include zymogens (inactive enzymes), water, and HCO3- Insulin and glucagon produced and released by pancreas (endocrine secretions). Zymogens - inactive precursor forms of enzymes such that they can only be activated in lumen of small intestine Trypsin activates many zymogens. Trypsin starts out as trypsinogen and converted to trypsin by enteropeptidase.

Natriuretic Peptides

The atrium secretes natriuretic hormones when myocardial cells stretch more than usual. They decrease Na+ (and water) reabsorption by four pathways which causes a decrease in blood pressure. 1) Decrease vasopressin release from hypothalamus which increases excretion of NaCl and water which decreases blood volume and therefore pressure. 2) In kidney, decrease sodium reabsorption and dilates afferent arteriole which increases GFR which increases sodium and water excretion. Also decreased renin which decreases aldosterone release and decreases blood pressure. 3) Decrease aldosterone release from adrenal cortex to increase NaCl and H20 excretion. 4) Decreased sympathetic output from medulla oblongata to decrease blood pressure. Excretion of sodium by urine is natriuresis.

Intercalated Cells

The distal nephron (last 1/3 of the distal tubule and collecting duct) is important for secreting H+ (de novo HCO3- synthesis) so have specialized cells that have high concentrations of carbonic anhydrase. Type A Intercalated Cells: H+ secretion; de novo HCO3- synthesis. Combats acidosis. Type B Intercalated Cells: H+ reabsorption; HCO3- secretion. Combats alkalosis.

Kidneys

The kidney conserves water by limiting urine production to a small, highly concentrated volume. The kidney excretes excess water by producing a large volume of dilute urine. The kidneys control the final volume and concentration of the urine by altering H2O and Na+ reabsorption in the distal tubule and collecting duct. 180 L/day enters glomerulus at 300 mOsm. 54 L/day enters loop of Henle at the same osmolarity. 18 L/day enter distal tubule at 100 mOsm. 1.5 L/day leaves collecting duct and the osmolarity can range between 50-1200. The original volume is a third of what it was down the loop of henle but osmolarity stays the same. After loop of henle, osmolarity and volume changes. Water and electrolytes are reabsorbed.

Behavioral Mechanisms in Salt and Water Balance

Thirst (hypothalamus) - osmoreceptors initiate drinking when body osmolarity is above 280 mOsM. Act of drinking can decrease thirst even before a decrease in osmolarity. Salt appetite (hypothalamus) - Craving salty food when plasma Na+ concentrations drop. Avoidance behaviors - taking a nap in a cool dark place to retain water.

Reabsorption of Bicarbonate

The kidney reclaims all filtered HCO3- in the proximal tubule to prevent body fluid pH from falling. 1) NHE sodium proton exchanger. Secretes protons into lumen against concentration gradient with anti transport of Na+ into cell. 2) H+ combines with bicarbonate to form bicarbonic acid and then CO2 using carbonic anhydrase. 3) CO2 diffuses into the cell. 4) In the cell, CO2 combines with H2O to form bicarbonic acid which is broken into H+ and bicarbonate. 5) H+ just created can be secreted into the lumen again, and can be combined with another filtered bicarbonate or be buffered with a phosphate ion and secreted. 6) Bicarbonate is reabsorbed into the blood with the cotransport of Na+. 7) Glutamine in cell is broken into alpha ketoglutarate and two amino groups. Amino groups converted to ammonium ion (NH4+) 8) NH4+ secreted into lumen and excreted. Alpha ketoglutarate metabolized to bicarbonate which is reabsorbed. Net Result: excretion of protons and reabsorption of sodium bicarbonate (baking soda).

Large Intestine

The large intestine (colon) absorbs remaining water from the chyme. Last steps of reabsorption. Ascending transverse and descending colon.

Pancreatic Bicarbonate Secretion

The pancreas secretes HCO3- into the duodenum to buffer H+. High levels of carbonic anhydrase to help with bicarbonate and hydrogen production. Bicarbonate secretion into duodenum neutralizes acid coming from stomach. Chloride enters cell as bicarbonate leaves cell through exchanger on apical side or by indirect active transport on basal side. Chloride can leave through CFTR on apical side. Movement of chloride into lumen attracts Na+ into lumen through leaky junctions. Water follows. Net effect - production of salty water.

Interstitial Osmotic Gradient

The renal medulla maintains high osmotic concentration in its cells and interstitial fluid. Allows urine to be concentrated as it flows through the collecting duct. Renal cortex has osmolarity of 300 mOsm so filtrate is isosmotic to interstitial fluid and reabsorption in the proximal tube is isosmotic. Isosmotic fluid leaving proximal tubule becomes more concentrated in the descending limb of loop of Henle since only water is being reabsorbed. So reduced volume and more concentrated. Tubule fluid at the bottom of the loop is the same as medulla osmolarity (1200 mOsm). In the ascending limb, solutes are removed to create a hyposmotic fluid (100 mOsm). Permeability to water and solutes in distal tubule and collecting duct is regulated by hormones. Final urine osmolarity depends on reabsorption in the collecting duct.

Renin-Angiotensin Pathway

The renin-angiotensin-aldosterone system regulates extracellular sodium levels. Begins when juxtaglomerular granular cells in the afferent arterioles secrete renin. Renin converts inactive angiotensinogen to ANG 1 which is converted into ANG II by angiotensin converting enzyme (ACE). ANG II travels to adrenal gland and causes release of aldosterone which travels to distal tubule and causes reabsorption of Na+. Reabsorption of Na+ increases osmolarity and stimulates thirst. This increases ECF volume and increases blood pressure.

Ventilation regulates pH

The respiratory system can regulate body fluid pH by regulating CO2 levels, which directly determines carbonic acid concentrations. During hypoventilation, PCO2 increases so equation shifts to the right and more H+ ions. More acidic pH. During hyperventilation, pCO2 decreases so equation shifts to the left and less H+ ions. More basic pH.

Cephalic and Gastric Phase Secretion

The stomach secretes HCl, enzymes, paracrines, and endocrines during the cephalic and gastric phases. Increased production of gastrin. Gastrin secreted in response to peptides in stomach. Secreted by G cells in gastric glands and triggers production of protons which acidifies stomach environment. Important because enzymes work best in acidic environment. Histamine also increases acid secretion by binding to H2 receptors on parietal cells. Pepsin secreted as inactive pepsinogen by chief cells in gastric acids. Pepsin breaks down proteins. Need a way to shut down the loop. This happens with Somatostatin which shuts down gastrin and histamine secretion and inhibits pepsinogen secretion.

pH Homeostasis

Three Mechanisms: kidney, lungs, intrinsic buffers (all maintain pH) pH= -log [H+] pH 6: 10-6 M = 1 µM H+ pH 7: 10-7 M = 0.1 µM H+ pH 8: 10-8 M = 0.01 µM H+ Normal pH is 7.4. Anything below 7 or above 7.7 is incompatible with life. Drastic change in pH influences protein structure which is why range is kept so little. Mitochondria - pH around 8 Lysosome - pH 5 Intracellular pH is different depending on organelle.

Type A Intercalated Cells

Type A intercalated cells secrete H+ during acidosis using H+ ATPase rather than Na+/H+ anti-port protein and synthesize new HCO3- to produce a compensatory alkalosis. If acidosis is persistent, then new HCO3- can be generated in the proximal tubule by formation of ammonium from glutamine metabolism (aka renal ammoniagenesis)

Type B Intercalated Cells

Type B Intercalated Cells secrete HCO3- and reabsorb H+ during alkalosis to produce a compensatory acidosis. H+ is reabsorbed into ECF/blood and HCO3- secreted into lumen.

Urea Recycling

Urea recycling contributes to the medullary osmotic gradient. Urea leaves collecting duct and goes back into ascending limb of Henle. Urea is a waste product that maintains the horizontal gradient. Protein catabolism results in amino acids which undergo deamination to produce ammonia. Ammonia is toxic so gets converted to urea.

Body Water Content

Water content of body can vary (it decreases with age and tends to be higher in males than females). It can be 45-65% of body weight. 28 L of ICF and 14 L of ECF so 42 L has to be regulated.

Water Balance in the Body

Water gain: through food and drink (2.2 L/day) and through metabolism (0.3 L/day). Water Loss: Through skin and breathing aka insensible water loss (0.9 L/day), through urine (1.5 L/day) and through feces (0.1 L/day). Total in and out is 2.5 L/day.

Respiratory Alkalosis

a loss of H+ from the body fluids caused by excess CO2 removal. Less common. pH increases (H+ decreases) and bicarbonate and partial pressure of CO2 decreases. Causes: hyperventilation (anxiety, altitude) Increased alveolar ventilation in the absence of increased metabolic CO2 Excessive artificial ventilation Anxiety (remedied by the' paper bag trick') Paper bag trick to increase CO2 back into system. Minimize CO2 loss to reverse alkalosis Renal compensation - bicarbonate excretion and H+ reabsorption.

Metabolic Alkalosis

a loss of H+ from the body fluids unrelated to CO2 flux. Rare compared to acidosis. pH and bicarbonate increases. Causes: Excessive vomiting Alkaline tide Loss of acidic stomach contents Ingestion of antacids Respiratory compensation - hypoventilation to increase CO2 and increase H+ and HCO3-.

Respiratory Acidosis

an accumulation of H+ in the body fluids resulting from CO2 accumulation. pH decreases and bicarbonate and partial pressure of CO2 increases. Causes: Hypoventilation Respiratory depression due to drugs Increased airway resistance in asthma Impaired gas exchange (e.g. fibrosis, pneumonia), COPD Muscle weakness (ex. muscular dystrophy) Renal compensation includes H+ secretion and HCO3- reabsorption.

Metabolic Acidosis

an accumulation of H+ in the body fluids unrelated to CO2 flux. Dietary & metabolic H+ input exceeds H+ excretion. pH decreases, H+ increases, bicarbonate decreases. Causes: Lactic Acidosis (anaerobic exercise) Ketoacidosis (Type I Diabetes) Methanol, aspirin Diarrhea (loss of bicarbonate) which prevents reabsorption of bicarbonate so it cannot buffer H+. pCO2 is normal or even decreased because of respiratory compensation (hyperventilation).

Buffer

any solute that resists a change in pH when H+ is added or removed from a solution Examples: proteins, phosphate ions, hemoglobin Buffers found within cell and in plasma and mostly combine with H+. Most important extracellular buffer of the body is plasma bicarbonate which is produced in very high concentration from metabolic CO2. Bicarbonate can only act as a buffer to H+ when it combines to form carbonic acid. Lower pKa means more likely to give away protons (stronger acid)

Bile Salts

make fats soluble during digestion by breaking down large fat droplets into smaller particles. Bile salts are amphipathic. Enzymatic fat digestion carried out by lipase and colipase which break down triglycerides into on monoglyceride and two fatty acids which form micelles. Fats move out of micelle and are absorbed by simple diffusion. Cholesterol transported using transport proteins. Triglycerides combine with cholesterol and proteins to form chylomicrons (large droplets) which leave the cell via exocytosis and enter lymph vessels. Pass through lymphatic system and enter venous blood right before it enters right side of heart.

Isotonic NaCl Secretion

occurs in salivary glands, the small intestine, and colon. Chloride enters cells from the ECF through NKCC transporters and enters lumen through CFTR channel. Sodium follows movement of chloride into lumen. Water follows so that the secretion is isotonic saline. This helps lubricates the bolus. CFTR is essential; absent or defective in cystic fibrosis

Aldosterone

regulates sodium absorption in last 1/3 of distal tubule and cortical collecting duct. Aldosterone is produced by adrenal cortex and is a steroid hormone (hydrophobic) will be bound to a carrier protein and will act on intracellular receptor. Aldosterone acts on principal cells (P cells). It increases expression of Na/K ATPase, located on basolateral membrane and activity of sodium (ENaC) and potassium leak channels (ROMK) located on apical membrane. Aldosterone released in response to hyperkalemia (increased K+ concentration). Enters P cells by simple diffusion. Once it binds to cytoplasmic receptor, it increases permeability of leak channels so intracellular Na+ increases, which increases activity of Na/K pump. The pump transports Na+ into ECF/blood and brings K+ from ECF into P cell. Net result is rapid increase in Na+ reabsorption and K+ secretion. Slow phase of response is that new channels are made and inserted into plasma membrane.