Final Exam Physiology (Ch 17-20)

Ch 17 

Physiology of the Kidneys

Renal System 

• Renal: pertaining to the kidneys

• Main function of system is regulation of extracellular fluid (ECF) environment in the human body through urine formation 

• Via this function, the renal system:

  • Regulates blood volume

  • Eliminates organic waste products of metabolism: urea (protein breakdown), uric acid (nucleic acids), creatine (muscle creatine), end products of hemoglobin breakdown 

  • Regulates balance of electrolytes (Na +, K+, HCO3-, other ions)

  • With respiratory system, maintains acid base balance/pH of plasma

Structures

• Kidneys (2)

  • Formation of urine

  • Water and electrolyte balance

  • Secretion of toxins and drugs into urine

  • Gluconeogenesis: synthesis glucose from AAs during prolonged fasting (also occurs in liver)

• Ureters (2) 

  • Transfer of urine to bladder

• Urinary Bladder

  • Storage and micturition (urination) via the urethra 

• Urethra 

  • Flow of urine from bladder to outside (micturition)

Female Renal System 

• The paired kidneys form a filtrate of the blood that is modified by reabsorption and secretion. Uring destined for excretion moves from the kidneys along the ureters to the bladder. It is then excreted through the urethra 

Kidney: Cross Section 

• Outer layer of the kidney is the Renal cortex; it is the site of glomerular filtration as well as the convoluted tubules

• Inner layer of the kidney is the renal Medulla; this is the location of the longer loops of Henle, and the drainage of the collecting ducts into the renal pelvis and ureter

Micturition 

• Contractions of smooth muscle in ureter wall cause urine to move from the ureter  to bladder 

• Bladder walls are smooth muscle (detrusor muscle)

  • Contraction of detrusor produces micturition 

• Internal urethral sphincter 

  • Smooth muscle is at base of bladder

• External urethral sphincter

  • Skeletal muscle is below this and surrounds the urethra 

  • Its contraction can prevent urination 

• Contraction and relaxation of these muscles is determined by:

  • Neuronal input, due to stretching of the bladder when it fills 

  • Voluntary decision making

Blood Vessels of the Kidney 

• Blood enters the kidney via the renal artery and exists via the renal vein. In the kidney there is extensive branching and capillary networks including the glomeruli 

The Nephron 

The functional unit of the kidneys, consisting of a renal corpuscle (glomerular capsule + glomerulus) and tubule

• >1,000,000 nephrons per kidney 

• Blood enters kidney through renal artery 

• Branching of renal artery -> afferent arterioles which bring blood to the glomeruli (a glomerulus is a capillary network in renal corpuscle

  • Blood from renal artery -> afferent arterioles -> glomeruli

• Twenty percent of plasma from glomerulus filters out of glomerulus and glomerular capsule and then moves into tubule

  • Filtrate from glomerulus -> glomerular capsule -> tubule -> collecting ducts -> renal pelvis -> ureters

• Blood remaining in glomerulus (80% of blood ) exists renal corpuscle through efferent arteriole to the peritubular capillaries

  • This blood drains into vein that exit the kidney as a renal vein

    • 80% of blood in glomerulus -> efferent arteriole -> peritubular capillaries -> renal vein 

Glomerular capsule or Bowman”s capsule:

• Surrounds glomerulus

• Fluid filters out of glomerulus into capsule

Proximal convoluted tubule:

• Filtrate from glomerulus enters lumen of tubule

• Reabsorption of salt, water, ect. Into peritubular capillaries that surround tubule

• Secretion of substances into filtrate

  • Descending limb of loop of Henle (some reabsorption)

  • Ascending limb of loop of Henle

  • Collecting duct

    • Distal convoluted tubule empties into it 

    • Duct drains into renal pelvis and then into ureters

Glomerular FIltration 

• Filters through large pores in glomerular capillaries called fenestrae

• Filtrate (or ultrafiltrate) is cell-free and mostly protein free; otherwize similar to plasma

Reabsorption of Salt and Water

• GLomerular filtrate is around 180 L each day, but urine excretion is only around 1-2 L per day 

  • 1% of this filtrate is excreted as urine and 99% of filtrate returns to vascular system (reabsorbed) to maintain blood volume and pressure

  • Reabsorption: return of filtrate from tubules of peritubular capillaries, via osmosis

• Urine volume varies depending on fluid needs of body (to maintain blood volume and pressure), so volume of fluid reabsorbed varies

• Most salt and water in filtrate are reabsorbed in proximal tubules. Some reabsorbed in descending limb of loop of Henle

Filtration & Reabsorption 

1. Filtration refers to the movement of fluid and solutes from the glomerulus into the capsule and then the tubules

2. Reabsorption refers to the movement of materials from the tubules into the peritubular capillaries, i.e. back into general circulation 

Reabsorption of Salt & Water in Proximal Tubule

• Na+ is actively transported out of filtrate and CI- follows passively by electrical attraction. Due to osmosis, water follows the salt into peritubular capillaries

Countercurrent Multiplier System

• For water to be reabsorbed into bloodstream by osmosis, ISF surrounding tubule must by hypertonic (causing water to move out of tubule)

  • Fluid is hypertonic due to Countercurrent Multiplier System 

  • Countercurrent (opposite direction flow) in ascending and descending limbs in nephrons and close proximity of limbs allows them to interact to create high osmotic pressure in ISF

• In ascending limb of the loop of Henie:

  • Na+ is actively pumped into ISF

  • CI- follows Na+ because of electrical attraction 

  • Not permeable to water so fluid in ascending limb becomes diluted 

  • NaCI accumulates in the ISF here, increasing the osmolarity of ISF so that reabsorption occurs in the descending limb 

• In descending limb of the loop of Henie:

  • Permeable to water but not salt 

  • ISF is hypertonic compared to filtrate here, so water leaves descending limb by osmosis -> ISF -> capillaries

  • Hypertonic fluid then enters the ascending limb, where Na+ is actively pumped out and CI- follows, creating diluted tubular fluid and more concentrated ISF

1. Extrusion of NaCI from ascending limb makes ISF more concentrated here. Na+ is pumped out and CI- follows due to electrical attraction 

2. In descending limb, water diffuses out via osmosis (and enters capillaries). This increases osmolarity of tubular fluid and decreases its volume as the fluid descends

3. Fluid at the bend of the loop has a high osmolarity, 1200 mOsm. The “saltiness” of the ISF is “multiplies” here because of the lack of permeability to water

Role of Osmoreceptors in ADH

• Changes in water intake alter plasma osmolarity, which is sensed by hypothalamic osmoreceptors

• Secretion of ADH is altered to affect water reabsorption in the kidneys. This affects the volume of urine excreted, to maintain blood volume 

Renal Plasma Clearance 

• Volume of plasma that is “cleared” of a substance by kidneys per unit time (i.e. substance is removed from plasma)

  • Substances are removed from plasma via filtration from glomerulus, or secretion into filtrate

    • Secretion is the movement of substances from the peritubular capillaries into the tubular fluid, for excretion in the urine

  • Reabsorptiion of a substance reduces its clearance

• Filtered glucose and AAs are completely reabsorbed in proximal tubule cia active transport 

• When the concentration of glucose exceeds the capacity of the transports, i.e. the transport maximum, the excess glucose is excreted in the urine = glucosuria

  • Occurs when plasma glucose concentration is too high, 180-200 mg/dl, e.g. in diabetes mellitus

Renal Control of Na+/K+ Balance 

• Much of the filtered Na+ and K+ is reabsorbed in early part of nephron 

• Concentration of Na+ and K+ in the urine excreted depend on physiological needs/homeostasis, and are adjusted late in nephron 

• Decreased plasma [Na+] activates renin-angiotensin-aldosterone system -> secretion of aldosterone (adrenal cortex)

  • Stimulates Na+ reabsorption, to increase plasma [Na+]

  • Causes passive reabsorption of CI- 

  • Water follows via osmosis to increase blood volume 

  • Aldosterone also stimulates K+ secretion into filtrate when plasma [K+] is high

• Potassium is filtered from the glomerulus. Some is reabsorbed in proximal convoluted tubule

  • Aldosterone stimulates potassium secretion in collecting duct when plasma [K+] is high 

Homeostasis of Plasma Na+

• ADH regulates water reabsorption to regulate urine volume and blood volume 

• Renin-angiotensin-aldosterone system stimulates secretion of aldosterone when Na+ intake is low

• Aldosterone stimulates Na+ reabsorption in the cortical collecting ducts

Renal Control of Acid/Base Balance

CO2+H2O ⇆ H2CO3 ⇆ H++HCO3(-)

• Kidneys regulate blood pressure pH by excreting H+ in the urine and by reabsorbing bicarbonate into the bloodstream.

  • Urine is slightly acidic because almost all of the filtered bicarbonate is reabsorbed

• In acidosis (pH < 7.35), there is increased plasma [H+] and more H+ in filtrate. Bicarbonate is synthesized in the proximal tubule, and absorbed into the bloodstream 

• In alkalosis (pH > 7.45), there is decreased plasma [H+] and less H+ in filtrate, so less bicarbonate is reabsorbed to compensate 

Ch 18

The Digestive system 

Function 

Processes food into molecular forms that are transferred into the internal environment, which the circulatory system distributes to cells 

• Motility 

  • Movement of food through the gastrointestinal (GI) tract via ingestion, mastication, deglutition, and contraction of smooth muscle (peristalsis & segmentation)

• Digestion 

  • Chemical/mechanical breakdown of food from macromolecules to smaller molecules, for absorption 

• Secretion 

  • Release of exocrine and endocrine secretions into lumen of GI tract for digestion and regulation of digestion 

• Absorption 

  • Movement of digested end products into blood and lymph 

• Storage and Elimination 

  • Temporary storage followed by elimination of indigestible food molecules (waste)

• Immune Barrier

  • Physical barrier to pathological organisms and toxins due to tight junctions in epithelial lining of intestine

  • As GI mucosa (mucous membrane) is in contact with the external environment, almost 80% of immune system cells are here 

Digestion via hydrolysis Reaction 

• Digestion of food molecules occurs by hydrolysis reaction, the chemical breakdown of substance involving reaction with water

Structures 

• Gastrointestinal (GI) Tract (ALimentary Canal)

  • Mouth, pharynx, esophagus, stomach, small intestine (SI), Large intestine (LI)

  • Appx 30 ft long

• Accessory organs and tissues

  • Teeth, tongue, salivary glands, liver, gallbladder, pancreas

Four layer/tunics of the gut wall

1. Mucosa (innermost layer)

2. Submucosa

3. Muscularis

4. Serosa (outermost layer)

The First (innermost) Layer

Mucosa:

• Absorption and secretion

• Mucus secretion

Layers:

• Epithelium 

• Lamina propria:

  • Connective tissue with lymphoid nodules

• Muscularis mucosae: thin smooth muscle layer, numerous small folds to increase surface area for absorption 

  • Produces movement of villi and brush border of small intestine

The Second Layer

Submucosa:

• Connective tissue

• Blood/lymph vessels

• Submucosal plexus: neuronal innervation for muscularis mucosae

The Third Layer

Muscularis Externa:

• Involved in segmental and peristaltic contractions, to move food through tract, and pulverize and mix it with digestive enzymes

• Inner circular layer of smooth muscle

• Outer longitudinal layer of smooth muscle

• Myenteric plexus: neurons for GI tract

The Fourth (Outermost) Layer

Serosa:

• Connective tissue covered with epithelium 

From Mouth to Stomach 

• Mastication: chewing of food in mouth 

  • Mixes food with saliva secreted by salivary glands

  • Digestion starts with saliva which contains salivary amylase, an enzyme that catalyzes the partial digestion of starch

• Deglutition: swallowing 

  • Initiated when food or drink stimulates pressure receptors in the pharynx 

  • The muscles of the mouth and tongue mux the food with saliva to create a bolus 

  • The tongue pushes the bolus to the back of the pharynx

  • The upper esophageal sphincter relaxes

  • Food descends into the esophagus

• Esophagus

  • Muscular tube connecting pharynx to stomach, posterior to trachea

  • Lined with epithelium and skeletal and smooth muscle

  • Peristalsis: wave like muscular contraction that push bolus to the stomach 

    • Circular smooth muscle contracts above the bolus and relaxes below it 

    • Then, there is shortening of the tube by longitudinal muscular contraction 

  • Food passes through lower esophageal sphincter to enter stomach 

• Stomach 

  • Digestion here results in chyme, partially digested food mixed with gastric juice

  • Stores food

  • Kills bacteria with acidity of gastric juice

  • Starts digestion of proteins

  • Peristaltic wave mix and propel the chyme 

  • Moves to small intestine, where most digestion and absorption occur

Stomach 

• Specialized cells in the stomach synthesize and secrete mucus, enzyme precursors, hydrochloric acid (HCI), and hormones

• The inner surface of the stomach contains folds called Gastric rugae

• The abundant smooth muscle in the stomach is responsible for gastric motility, the movement of food

Gastric Glands in Stomach 

• The gastric glands of the mucosa contain various cell types:

  • Mucous neck cells: secrete mucus

  • Parietal cells: secrete hydrochloric acid (HCI)

  • D cells: secrete somatostatin (hormone that inhibits parietal cells)

  • Chief (zymogenic) cells: secrete pepsinogen, an inactive form of pepsin (a protein-digesting enzyme)

  • Enterochromaffin-like (ECL) cells: secrete histamine and serotonin, for regulation of the GI tract 

  • G cells: secrete gastrin (hormone that stimulates parietal and ECL cells)

• Intrinsic factor, a polypeptide essential for intestinal absorption of vitamin B12 (needed for production of RBCs in bone marrow)

• Ghrelin, a hormone that regulates hunger

• Gastric juice = secretions of gastric cells + water

Gastric Glands

• Chief cells synthesize and secrete pepsinogen, the pepsin precursor

• Parietal cells synthesize and secrete the hydrochloric acid (HCI) responsible for the acidic pH in the gastric lumen 

Activation of pepsin 

• The acidity in the gastric lumen (pH < 2) converts pepsinogen (from chief cells) to pepsin. Pepsin partially digests proteins. Bicarbonate protects the stomach from acid damage

Small Intestine 

• Longest part of GI tract, 3m long (small diameter)

• Digestion of carbohydrates, lipids, protein

  • Brush border enzymes and pancreatic enzymes

• Absorption of carbohydrates, lipids, AAs, vitamins, minerals, iron, water, electrolytes, and bile salts, into the bloodstream.

• Folds in mucosa are called villi

  • Microvilli, or brush border, on the villi increase the surface area for absorption 

  • Brush border enzymes are embedded in microvilli and are exposed to chyme

Brush Border Enzymes

• Brush Border enzymes are embedded in the plasma membrane of the microvilli. Their active sites face the chyme in the lumen of the SI

Contractions & Motility in SI

• Motility in SI is slow, to ensure proper absorption of nutrients

• There is some peristalsis

• Main contraction in SI is segmentation:

  • Muscular constriction of lumen that occur simultaneously in different segments 

  • Mixes and moves chyme

Large Intestine/Colon 

• Large diameter

• No villi

• Haustra are pouches on outer surface

• No digestion

• Absorption of electrolytes, water, vitamins

• Excretion of waste products in feces, through rectum and anal canal

Fluid & Electrolyte absorption in LI

• Around 1.5 L water from food and drink enters GI tract per day

• GI tract also secretes around 8-10 L of fluid into its lumen 

  • From salivary glands, stomach, intestine, pancreas, liver, gallbladder

  • In LI, there is absorption of most of the fluid, so that < 200 ml of fluid is excreted in feces

    • Active transport of Na+ into epithelial cells of LI -> osmosis of water into ISF and then into bloodstream

Accessory Organs 

• Liver: many functions, including synthesis of bile

• Gallbladder: storage of bile from liver and release into SI

• Pancras: pancreatic juice for digestion in SI

Liver

• Detoxification of blood 

• Carbohydrate metabolism 

• Lipid metabolism

• Protein synthesis

• Secretion of bile

• Storage of molecules

Secretion of Liver

• Groups of liver cells, or hepatocytes, are separated by hepatic sinusoids

• Blood enters a liver lobule (functional unit) through portal triad (hepatic artery, portal vein, bile ductule), passes through hepatic sinusoids, and leaves the lobule through central vein

• Central veins converge to form hepatic veins that take venous blood away from the liver

• Bile is synthesized by hepatocytes and secreted into bile canaliculi. The canaliculi drain into bile ductules into portal triad

• The bile is funded from the ductules into the gallbladder where it is stored, and then delivered into the small intestine

Bile 

• Main components of bile, a yellow-green fluid: bile pigment (from breakdown of RBCs), bile acid or salts, lecithin (a lipid), a bicarbonate, cholesterol, and trace metals

• Bile acids are cholesterol-based, and form micelles in aqueous solutions

• In the SI, fat enters the micelles and the amphipathic property of micelles allows emulsification (or breakdown) of fat

  • Emulsification: breakdown of large fat globules by bile acids into smaller globules for digestion by lipase 

Circulation of Bile 

• Bile enters the small intestine via the common bile duct

• In the SI, the bile emulsifies fat to break them down before digestion by lipase

Pancreas 

• Endocrine functions: insulin, glucagon 

• Exocrine functions: pancreatic juice

  • Synthesized by acinar cells and delivered to duodenum of SI through pancreatic duct

• Pancreatic juice is bicarbonate and around 20 enzymes:

  • Amylase: digest starch 

  • Trypsin: digestion protein

  • Lipase: digest triglycerides

  • Many of enzymes are activated in the SI

  • Pancreatic enzymes and brush border enzymes accomplish complete digestion of food molecules in SI

Pancreatic Secretions

• The Exocrine cells in the pancreas produce digestive enzyme that exit cia the pancreatic duct to travel to the small intestine

• If digestive enzymes secreted by the pancreas were synthesised in their active form, they would digest the very cells that make them. Hence, inactive precursors (zymogens) become activated in the small intestine

Digestion & Absorption of Carbohydrates

• Daily intake is 250-300 g, mostly as starch, a polysaccharide of glucose

• Most commonly ingested sugars are sucrose and lactose

• Salivary amylase starts digestion in mouth

• Pancreatic amylase in SI (most of carb digestion) results in maltose, maltotriose, and oligosaccharides

• Brush Border Amylases in SI hydrolyze these sugars  into their component monosaccharides, which are then moved across the brush border membrane by active transport, to be absorbed into the bloodstream

Pancreatic Amylase 

• Brush border enzymes hydrolyze these short molecules into their component monosaccharides, which are then moved across the brush border membrane by active transport, to be absorbed into the bloodstream

Digestion & Absorption of Proteins

• Daily intake is 60-90 g (needed for AAs)

• In stomach, pepsin produces short-chain polypeptides

• In SI, pancreatic enzymes trypsin, chymotrypsin, and carboxypeptidase, and brush border enzyme aminopeptidase digest polypeptides into free AAs, dipeptides, and tripeptides

• AAs enter epithelial cells of SI by active transport and are secreted into ISF and then absorbed into capillaries 

Digestion & Absorption of Lipids

Daily intake is 70-100 g (mostly fat)

1. In SI, bile emulsifies fats

2. Pancreatic lipase liberated free fatty acids and monoglycerides via hydrolysis

3. Free fatty acids and monoglycerides are in mixed micelles

4. Fatty acids and monoglycerides from micelles enter the epithelial cells of the SI. There, they are resynthesized into triglycerides

5. Triglycerides combine with protein to form chylomicrons, which enter lymphatic vessels and eventually enter veins (blood)

Ch 19 

Glucose Tolerance

Control & Integration of Carbohydrate, Protein, & Fat Metabolism 

• Here, metabolism is defined as all of the chemical reactions in the body 

• Plasma contains circulating glucose, fatty acids, and AAs used by the body's cells for the production of energy via cell respiration 

• There are energy reserves in cells, such as triglycerides, carbohydrates, and proteins. They are broken down via catabolism 

• Glucose concentration in the blood must be maintained in a normal, healthy range for the production of energy 

• Complete absorption of an average meal takes around 4 hours

• There are energy reserves (stores, storage) that are synthesized after a meal, via anabolism 

Absorptive & postabsorptive States

• There are two functional states for providing energy for cellular activities and maintaining blood glucose concentration:

  • Absorptive State: “feeding/fed”, when nutrients are absorbed into the bloodstream from the GI tract during the 4 hour period following a meal

  • Postabsorptive State: “Fasting,” after the absorptive state, when the GI tract is empty of nutrients and the body reserves supply energy 

Regulation of States

• Glucagon and insulin are hormones that regulate the transition between fasting and feasting and maintain homeostasis of glucose

• Apla cells of pancreatic islets (islets of Langerhans) secrete glucagon

• Beta cells of pancreatic islets secrete insulin 

Absorptive State

• Carbohydrates are absorbed into the bloodstream from the GI tract as monosaccharides, increasing blood glucose concentration

• Insulin: Increased secretion during absorptive state, when blood glucose is high (140-150 mg/dl)

• Glucose: body's major energy source during absorptive state

  • Insulin promotes cellular uptake of glucose 

  • Insulin promotes storage of glucose as glycogen in liver and muscles = Glycogenesis (anabolism)

  • In cells, glucose is catabolized to CO2, H2O, and ATP during cell respiration 

  • Adipose tissue cells (adipocytes) transform glucose to fat (triglycerides) which is stored in adipose tissue = lipogenesis (anabolism)

  • In the liver, glucose is also transformed into triglycerides, to be stored in adipocytes = lipogenesis

• Proteins: are absorbed into the blood from the GI tract as AAs

  • Insulin promotes cellular uptake of AAs and their incorporation into proteins = protein synthesis (anabolism) 

  • Protein synthesis occurs in liver and many other tissues 

• Lipids: are absorbed into lymph as chylomicrons 

  • Insulin promotes conversion of lipids + glucose into triglycerides to be stored in adipose tissue = lipogenesis (anabolism)

  • Cholesterol from chylomicrons is a component of plasma membranes, and a precursor for bile and steroid hormones 

Postabsorptive State 

• Synthesis of glycogen, triglycerides, and proteins ends

• Catabolism of reserves begins due to secretion of glucagon

Glucagon

• Increased secretion during postabsorptive state, when blood glucose is low (fasting blood glucose of 65-105 mg/dl)

  • Glycogenolysis: hydrolysis of glycogen in liver to increase blood glucose (glucose from glycogenolysis in skeletal muscle in used locally) 

  • Gluconeogenesis: synthesis of glucose from AAs, glycerol pyruvate, and lactate, in liver and kidneys 

  • Glucose sparing: most tissues (except nervous) can use free fatty acids (from lipolysis) for energy instead of glucose 

Postabsorptive State 

• Ketogenesis in liver during prolonged fasting 

  • Synthesis of ketone bodies from fatty acids

  • Used as an alternative energy source during prolonged fasting (esp. Nervous tissue) 

• Protein catabolism in all tissues = breakdown of proteins into AAs

• Lipolysis, the breakdown of stored fat 

Catabolism during Postabsorptive state 

• During fasting, insulin secretion decreases and glucagon secretion increases

• There is release of glucose, fatty acids, ketone bodies, and AAs into the blood. The liver also releases glucose synthesized by gluconeogenesis

Diabetes Mellitus

• Chronic high blood glucose, hyperglycemia

• Two types

  • Type 1 diabetes mellitus (T1DM, insulin-dependent)

  • Type 2 diabetes mellitus (T2DM, non-insulin-dependent)

• 3Ps: polyuria, polyphagia, polydipsia

Type 1 Diabetes 

Insulin deficiency due to autoimmune destruction of beta cells, so insulin must be injected, pumped or, inhaled

• Genetic & environmental causes 

• Hyperglycemia occurs because cellular uptake of glucose in impaired with lack of insulin 

• Glycosuria occurs because amount of glucose filtered into urine exceeds maximum for reabsorption in kidneys

• Ketosis: ketone body concentration is elevated because increased lipolysis (due to lack of insulin) releases fatty acids, which are converted to ketone bodies (acidic)

  • Ketoacidosis and (ketone breath) can occur if there is not enough bicarbonate to neutralize acid from ketone bodies 

• Excessive excretion of water in urine because excessive glucose and ketone bodies in urine cause osmotic diuresis

Type 2 Diabetes 

Insulin is present but target cells are resistant to insulin, so blood glucose concentration remains high

• Most common form of diabetes (around 90% of diabetics)

• Usually begins in adulthood (although often occurs in childhood nowadays) 

• Common in obese individuals because insulin sensitivity is reduced by the presence of excess adipocytes

• The best treatment is weight reduction and exercise to increase insulin sensitivity in target cells

• Drug treatments also improve insulin sensitivity 

Effects of Diabetes 

• Tissue damage 

• Peripheral nerve damage leads to decreased sensation in the extremities

• Damage to capillaries in eyes and kidneys leads to blindness and kidney failure 

• Circulatory deficiencies may result in damage to the feet, injection, gangrene and may require amputation 

Untreated Diabetes 

Extreme Insulin Problems:

• Impaired response to or failure to secrete insulin shifts metabolic dependence to acid-generating ketones

• Hyperglycemia-induced diuresis reduces blood volume to the point of inadequate blood delivery to the brain 

Cholesterol 

• Sources:

  • Dietary, absorbed into the bloodstream from SI

  • Synthesized in liver

• Functions of cholesterol:

  • Found in plasma membrane

  • Basis for steroids and bile salts

  • In liver, combines with triglycerides and proteins to form VLDLs (very low density lipoproteins), which are secreted into the blood to deliver triglycerides to organs

  • Found in LDLs (low density lipoproteins), which carry cholesterol to organs, including blood vessel walls

    • LDL is the “bad cholesterol”

    • Excess -> atherosclerosis

  • Found in HDLs (high density lipoproteins), to which excess cholesterol from organs is attached to return it to the liver

    • HDL is the “good cholesterol”

Control of Food Intake 

• For regulation of total-body energy content and fat stores

• A key hormone for long-term regulation is leptin, which is synthesized in adipocytes and released in proportion to the amount of fat being stored

  • Acts on Hypothalamus to decrease appetite/food intake and increase metabolic rate 

• There are several other factors that affect hunger 

Factors Affecting Food Intake 

• The overall “equation” governing food appetite (hunger) includes a diverse set of inputs, suggesting that the problem of managing obesity will not readily lend itself to simple resolution 

Ch 20

Reproduction 

Some Terminology 

Gonads: testis and ovary 

Gametes: sperm and egg

Gametogenesis: Spermatogenesis (production of sperm) and oogenesis (production of egg)

Gonadotropic hormones: FSH (follicle-stimulating hormone), LH (luteinizing hormone)

Gonadal steroids: testosterone, estradiol, and progesterone

Meiosis: Chromosomes replicate and recombine, followed by two successive cell divisions resulting in 4 daughter cells, each with half the numbers of chromosomes (haploid) of the parent cell. Occurs in the gonads and creates gametes only.

Mitosis: Chromosomes replicated, followed by cell division that results in two daughter cells with the same number of chromosomes (diploid) of the parent cells. Daughter cells are genetically identical. Creates all body cells besides gametes 

Sexual Reproduction 

• In sexual reproduction, genes from two individuals are combined in random and novel ways with each new generation 

  • In each cell, there are 23 pairs of chromosomes, with one chromosome from each parent in each pair (46 chromosome stomatal each cell)

  • An individual's DNA is contained in these 46 chromosomes

  • Except for the sex chromosome, each pair contains two homologous chromosomes, meaning they look like each other and contain similar genes

  • Cells that contain 46 chromosomes (23 pairs) are called diploid 

  • Cells that contain 23 chromosomes are called haploid 

• At puberty, meiosis in the gonads results in gametes (sperm, egg)

  • Each gamete is unique and has 23 chromosomes (haploid) 

• During fertilization,  sperm cell and egg cell fuse to produce a fertilized egg (zygote), which is diploid 

• Mitotic cell divisions underline the growth of the zygote into an adult. IN mitosis two genetically identical diploid “daughter” cells are produced 

Sex Determination 

• Pairs 1-22 are autosomal (numbered) chromosomes

• Pair 23 is the sex chromosomes

  • X from mother

  • X or Y from father

  • Female: X X 

  • Male: X Y

Reproductive Endocrinology 

• During puberty, gonads secrete more sex steroid hormones, due to stimulation by gonadotropic hormoes (FSH, LH) from anterior pituitary glands

  • Testosterone

  • Estrogen 

  • Proesterone

• Three hormone sequence 

  • GnRn -> FSH and LH -> secrete sex hormones AND undergo gametogenesis

• Secretion of gonadotropins and sex hormones in females is cyclical (menstrual cycle)

Male Reproductive System 

Testes 

• Seminiferous tubules

  • Sertoli cells: spermatogenesis & secretion of inhibin (inhibits secretion of FSH)

• Lydig or interstitial cells (between tubules)

  • Secretion of testosterone

  • Sperm moves from the tubules into the rete testis, then into the efferent ductules, eididymis, and then the vas deferens

Accessory Organs 

• Duct system 

  • Epididymis, vas deferens, ejaculatory ducts, urethra

• Glands

  • Seminal vesicles, prostate gland, bulbourethral glands

  • Secrete fluid component of semen, in which sperm is suspended

• Secondary sexual structures

  • Penis, scrotum 

Hormonal Control of Male Reproductive Function 

Note the different effects of FSH and LH, both secreted by the anterior pituitary gland

• FSH stimulates spermatogenesis and secretion of inhibin by Sertoili cells in seminiferous tubules, whil LH stimulates Leydig cells to secrete testosterone 

• Testosterone has varied effects

Testosterone 

• Spermatogenesis 

• Stimulates anabolism -> growth of muscles an dother structures

• Increased testosterone secretion during puberty growth of accessory organs, larynx 

Spermatogenesis (64 days)

• Appx 300 million sperm cells produced each day in seminiferoud tubules 

• Speratogenesis are in outermost region of seminifeours tubules (diploid, 2n)

1.MITOSIS

• Spermatogonia duplicate via mitosis. One daughter cell becomes primary spermatocyte (2n)

2. First Mieotic Division 

• Primary spermatocyte divides into two identical secondary spermatocytes, each with 23 chromosomes (n) (with 2 identical chromatids per chromosome)

3. Second Meitoic Division 

• Results in spermatids (n)

4. Spermiogenesis:

• Spematids transform into spermatozoa (sperm cells) (n)

Seminiferous Tubule and Sertoli Cells 

• Sertoli cells in the tubule wall support spermatogenesis and protect developing sperm in the seminiferous tubules

Female Reproductive System

• A spermatozoan ejaculated into the female reproductive tract must move through the cervix and uterus before it can fertilize an ovulated egg

Ovaries

• Oogenesis

• Synthesize and secrete estrogen, progesterone, inhibin 

• Ovarian (mothly) cycle:

  • Developmental sequence w/ovulation of one ovum and some follicular cells per month 

Monthly, an ovary releases an ovum that moves from the ovaries into the oviduct. Fertilized eggs are implanted in the uterus, where fetal development occurs

Accessory Organs

• Oviducts/Fallopian Tubes/Uterine Tubes

  • Transport released ovum plus some follicular cells via ciliary action and smooth muscle contraction

  • Usual site of fertilization 

• Uterus 

  • Usual site of implantation of fetal development 

  • Perimetrium (outmost layer, connective tissue) includes peritoneum lining the pelvic cavity 

  • Myometrium is a thick smooth muscle layer

  • Endometrium includes epithelial layers that are sloughed off during menstruation 

  • Narrows to form cervix, which opens to vagina

• Vagina

  • Path for sperm to ovum

Follicles 

• The zone pellucida is a thin, gel-like layer around the secondary oocyte. It presents a barrier to fertilization of an ovulated oocyte by sperm. The corona radiata is comprised of granulosa cells surrounding the zona pellucida

Menstrual Cycle 

• 28 day ovarian cycle and endometrial cycle

• Cyclical variations in luteinizing hormone (LH), follicle-stimulating hormone (FSH), progesterone, and estradiol (an estrogen)

• Ovulation occurs at around day 14 of cycle

• Menstration: shedding of epithelium of endometrium if ovulated egg is not fertilized; days 1-4 of cycle

Menstrual Cycle: Ovarian Cycle

• Follicular phase (Days 1-13)

  • Development of follicles under influence of FSH

  • One follicle matures to graafian follicle 

  • Increased estradiol secretion from granulosa cells

    • Leads to LH surge (from anterior pituitary) just prior to ovulation

• Ovulation (Day 14)

  • LH surge causes wall of graafian follicle to rupture at around day 14 

  • Secondary oocyte is released from ovary and swept by cilia into oviduct, toward uterus

• Luteal phase (day 15-28)

  • Transformation of follicle into corpus luteum (CL, yellow body) due to LH

    • CL secretes estradiol, progesterone (peaks during this phase)

    • If no fertilization, estradiol and progesterone decreases and CL turns into corpus albicans, causing menstruation

Hormonal Changes During Menstrual Cycle

• Small increases in the secretion of LH and FSH -> follicular maturation in the follicular phase and an increase in the synthesis and secretion of ovarian steroid hormones

• LH surge -> ovulation and luteal phase

  • High proesterone concentration 

Menstrual Cycle: Endometrial Cycle 

• Menstrual phase (days 1-4) 

  • As ovarian hormone secretion decreases, uterine blood vessels constrict rhythmically, depriving the tissue of blood 

  • Endometrium undergoes necrosis and is sloughed off, resulting in menstrual flow 

  • Myometrium contracts as well (cause of cramps)

• Proliferative phase (days 5-14)

  • Growth and maturation of endometrium under influence of estradiol from the follicle

• Secretory phase (days 15-28) 

  • Increased progesterone and estradiol from CL stimulate endometrial thickening, for implantation. If no implantation, estrogen and progesteron levels drop and shedding occurs

Fertilization 

• Mature sperm stored in epididymis

• Appx 300 million sperm ejaculated during intercourse

• Fluid pressue of ejaculate propels sperm into uterus

• Only around 100 survive and enter each oviduct (acidic vaginal environment, energy requirments of travel), and about 10% can fertilize an ovum

• Capacitation: ability to fetilize egg

  • Stimulated by high pH of femal tract

  • Results in whip-like action of tail to propel sperm forward toward oocyte

• Fertilizartion occurs in oviduct, due to short viability and slow transport of egg

• Time window:

  • 5 days before 1 day to ovulation, due to sperms ability to fertilize for 4-6 days, and egg viability for 24-48 hr

• Acrosome in head of sperm binds with zona pellucida of egg, triggering acrosome reaction:

  • Alteration of head membrane and release of acrosomal enzymes, to digest a path through zone pellucida to the oocyte

Early Development

• Zygote (fertilized egg) completes it second meiotic division -> diploid

• Undergoes cleavage = miotic cell division into 2 smaller cells

• Continued mitosis eventually results in morula (16 cells) at 50-60 hour after fertilization, which enters uterus 3 days after ovulation 

• By day 4, 32-64 cells. Then converted to blastocyt = inner cell mass ( to become fetus) + outer chorion (to become placenta) 

• On day 6, embryo attaches to uterine wall = implantation 

Placenta

• In weeks 1-10, blastocyt cells secrete human chorionic gonadotropin (hCG)

  • Maintains CL and secretion of estradiol and progesterone, and to prevent menstration

• CL regresses in week 5-6. And then placenta secretes proesterone and estrogen to maintain pregnacy

Placenta: organ of exchange of gases, nutrients, and waste between mother and fetus; develops in uterus 

• Interlocking fetal and maternal tissue with extensive blood supply

• Umbilical arteries (2) and vein (2) are in umbilical cord

Labor & Parturition 

• Labor: powerful uterine contractions to expel fetus

• Parturition: childbirth (delivery)

• Uterine contractions stimulated by oxytocin (uterus and hypothalamus/posterior pituitary) and prostaglandins (fatty acids, uterus)

• Proesterone secretion decreases

• Estrogen causes smooth muscle cells to reom gap junctions, so that the myometrium contracts as a single unit 

• Cervix is made soft and flexible by estrogen, prostaglandins, and relaxin (ovary)

Lactation

• Production and secretion of milk after birth 

• Mammary glands in breast produce and secrete milk

  • Surrounded by myoepithelial cells (contractile cells for milk ejection) and adipose tissue

  • They become secretory in early pregnacy due to progesterone, estrogen, and prolactin

Hormones:

• After parturition, increased prolactin stimulates mammary glands ot produce milk 

Suckling also causes secretion of prolactin and oxytocin, which result in secretion of milk into ducts, and ejection of milk, respectively