Physiology Part 4

Front 1

Glomerular Filtration Rate (GFR) hpic

Back 1

•Influenced by two factors

–Net filtration pressure

–Hydrostatic pressure

–colloid osmotic pressure

–fluid pressure

–Filtration coefficient

–Surface area of glomerular capillaries available for filtration regulated by mesangial cells

–Permeability of interface between the capillary and Bowman’s capsule

Hint 1

Front 2

Intrinsic GFR Regulation

Back 2

•Myogenic response

–Intrinsic ability of vascular smooth muscle to respond to pressure changes

–Similar to autoregulation in other systemic arterioles

•Tubuloglomerular feedback

–Paracrine control from the macula densa

–Too much flow (NaCl) at macula densa means GFR is too high

–Response is to constrict the AA

Front 3

Back 3

Front 4

Tubuloglomerular feedback

Back 4

•Macula densa is a chemoreceptor.

•If there is too much flow or too much NaCl delivery -> there is more work to do than the distal tubule can handle

•That means the GFR is too high.

•The Macula densa sends a chemical signal to constrict the AA so the GFR is brought down to level that is better for homeostasis

Front 5

Why regulate the GFR?

Back 5

•The GFR is the means by which the kidney cleans the blood. Plasma is filtered.. The useful substances are reabsorbed and the wastes are secreted and excreted...

•If the GFR is too low, the blood is not being cleaned?

•BUT if the GFR is too high, the tubules is not able to process the filtrate .... Valuable water and electrolytes could be lost in the urine... this would be a threat to blood pressure maintenance.

Front 6

Regulators of GFR hnotes

Back 6

•Tone of arterioles (Fig 19-6 c,d,e)

•Atrial natriuretic peptide dilates AA–GFR

•Blood pressure –hypotension↓ GFR

•Blood volume – dehydration–↓ GFR

•Constriction of Mesangial cells –↓ GFR

•Sympathetic stimulation -↓ GFR until BP can be returned to normal

•Angiogensin II –↓ GFR until BP can be returned to normal

Hint 6

Why is low GFR good? so you dont lose valuable liquids? maintaining blood pressure
why is high GFR also good? getting rid of waste products.

Front 7

LEARNING OBJECTIVES

Back 7

•Can you draw a nephron and label the parts?

•Can you explain the filtration process distinguish between freely filterable and non filtered substances?

•Can you explain how the myogenic response (auto

regulation) maintains the GFR in the face of changing pressure?

•How tubuloglomerular feedback ensures the GFR is not too high?

•How do extrinsic factors regulate the GFR?

Front 8

Back 8

Hint 8

1) exists a Na+ ATPase

2) chloride leak channel here (anion sneaks between cells, at a tight junction)

3) coming through aquaporines

4) they arrive after the other ones because new gradient has been formed.

(PARAcellular movement) sneaking between cells

Front 9

Reabsorption hnotes

Back 9

•Epithelial transport (transcellular transport)

–Substances cross apical and basolateral

membranes of the tubule epithelial cells

–The proximal tubule is responsible for the reabsorption of Na+, glucose, amino acids, Ca2+, and other electrolytes.

–Reabsorption is iso-osmotic because water follows particles.

•Paracellular pathway

–Substances pass through the cell

–cell junction between two adjacent cells

Hint 9

proximal tubule does roughly 66% of the filtration, rest goes to the loop of henle

Front 10

Back 10

Hint 10

notice that this is one of the few times that glucose must be diffused accross the entire cell.

Front 11

Secretion

Back 11

•Transfer of molecules from extracellular fluid into lumen of the nephron

–Active process

•Important in homeostatic regulation

–K and H

•Increasing secretion enhances nephron excretion

•A competitive process

–Penicillin and probenecid

Front 12

Excretion hnotes

Back 12

•Excretion = filtration

–reabsorption + secretion

•Clearance

–mL of plasma per minute cleared of a particular substance

–Measure of how fast the body gets rid of a substance

–Noninvasive way to measure GFR

–Inulin and creatinine are used to measure GFR

Hint 12

highly likely test question: be able to define clearance:

ITS BASED ON PLASMA, NOT THE URINE.

its a flow that measures the amount of plasma thats been cleaned

all forms of clearance has its own clearance rate

high clearance = something we normally get rid of

low clearance= something we normally dont get rid of.

Front 13

Clearance

Back 13

Front 14

Measuring GFR

Back 14

In your text, GFR is measured by the clearance of

inulin... this is true.

Best clinical measure of the GFR and renal function is the clearance of creatinine... this is how GFR is measured in clinical settings.

Why? Because creatinine is an endogenous

substance that is freely filtered, not reabsorbed and only slightly secreted.

Front 15

if you have a low blood volume

blood pressure and volume responses hpic

Back 15

causes lack of stretch in Atria. otherwise too high.

Hint 15

Front 16

if blood pressure and blood volume is too high.....

Back 16

Front 17

How kidneys can conserve water

Back 17

Front 18

Water Balance hpic (osmolarity changes in the nephron)

Back 18

•The kidneys cannot replenish lost water; all they can do is conserve it

•Diuresis: the removal of excess water in urine

–Diuretics: drugs that promote urine excretion

•Membrane recycling allows vasopressin/ADH to control which parts of the cell membrane are permeable to water in the distal tubule/collecting duct

Hint 18

Front 19

Loop transporter

Back 19

reabsorbs Cl, K, Na, and leaves H20 behind in the nephron. this happens around the loop of Henle. Aquaporins allow water to reabsorb into the body, the more there are, the more that are used.

Front 20

Long medullary Loops of Henle

Back 20

•Descending limb

–Permeable to water but not salt

–Filtrate becomes more concentrated as flows

deeper in medulla

•Ascending limb

–Permeable to salt but not water

–Filtrate becomes less concentrated as flow back

toward cortex

Front 21

where does that NaCl and KCl and water go

Back 21

•It enters the vasa recta capillary bed.

•Some of it leaves the medulla by the vasculature.

•Much of it stays in the medulla.......

•What keeps the particles in the medulla? countercurrent mechanimsm

Front 22

Vasopressin/ADH action to save water is the goal

Back 22

•The countercurrent makes the medulla hyperosmotic so that ADH can help a person save water if they need to for homeostasis.

•So let’s talk about the collecting duct first.

Front 23

ADH (anti-diuretic-hormone) helps you save water

Back 23

Front 24

Loop in the Vaso Recta partially obstrict K, Ca, and Cl from leaving medulla.

Back 24

this is also opposite of how it works in the loop of henle.

Front 25

Fluid and Electrolyte Balance

Back 25

•Vasa recta removes water

–Close anatomical association of the loop of Henle and the vasa recta

•Urea increases the osmolarity of the medullary interstitium

•Because urea is penetrating to RBC... the RBC do not shrink as much as they would in the presence of all non penetrating solute.

Hint 25

because there is so much urea in the medulla, it is hyperosmotic.

Saves the RBC from shrinking until its a raisin.

Front 26

response to eating salt

Back 26

Front 27

•How is the regulation of the ADH secretion a

negative feedback mechanism?

–What parameter is being monitored?

–What is the stimulus?

–What is the response of the body?

Back 27

parameter: ECF and osmolarity

stimulus:

response: ADH helps retain water

Front 28

Distal tubule/CD vs. Proximal tubule

Back 28

DistalTubule and Collecting Duct

•DT/CD fine tunes renal processes according to what is needed for Homeostasis

•Smaller amounts of Na reabsorbed

•K secretion

•Extensive Hormonal regulation

Hint 28

Proximal tubule

•PT is the work horse of the nephron doing the bulk of the work. (called the work horse b/c reabsorption of all the glucose) if you are hyperglycemic, often pee glucose and you have diabetes.

•2/3 of Na and water

•All glucose and aa

•Most drug secretion

•Some hormonal regulation

Front 29

Fluid and Electrolyte Homeostasis

Back 29

Front 30

Blood pressure Regulation is also part of homeostasis

Back 30

•Neural

•Baroreceptors: are Fast, good at Position changes

•Hormonal

•RAAS (renin attention aldosterone system) regulates sodium and volume, Slower than baroreceptors.

•Volume and Na+ changes

Front 31

RAAS

Back 31

•Renin is a kidney enzyme released from the juxtaglomerular apparatus

•Catalyzes the production of angiotensin I

•Angiotensin converting enzyme catalyzes the production of angiotensin II

•Angiotensin means “blood vessel contraction” Angiotensin II is a powerful vasoconstrictor.

•Ang II also stimulates the secretion of aldosterone (thirst, ADH secretion, cardiac effects).

•Both hormones raise blood pressure via negative feedback

Front 32

The primary action of aldosterone is renal sodium reabsorption.

Back 32

Hint 32

Q: Notice that elevated plasma K+ also stimulates aldosterone. Why is this beneficial?

ANS: Cardiac regulation. we dont want depolarization, we need normal resting potential.

Extra cellular Potassium: normally at 4mM, at 6mM it hurts, at 10mM you are dead. aldosterone saves you.

Front 33

Aldosterone is a steroid Works via gene transcription

Back 33

Front 34

If blood pressure is

too low

Back 34

1.Baroreceptors are less stretched and activate sympathetic afferents.

2. The afferent arteriole is less stretched.

3.The GFR decreases and less NaCl/flow arrives at the macula densa

Front 35

Potassium Balance

Back 35

•Regulatory mechanisms keep plasma potassium in narrow range

–Aldosterone plays a critical role

•Hypokalemia

–Muscle weakness and failure of respiratory muscles and the heart

•Hyperkalemia

–Can lead to cardiac arrhythmias

Front 36

Acid–Base Balance

Back 36

•Normal pH of plasma is 7.36 –7.44

•H+ concentration is closely regulated

–Changes can alter three

-dimensional structure of proteins

•Abnormal pH affects the nervous system

–Acidosis: neurons become less excitable; CNS depression

–Alkalosis: hyperexcitable

•pH disturbances

–Associated with K+ disturbances

Hint 36

Front 37

Acid and Base Input

Back 37

•Acid

–Organic acids

–Diet and intermediates

–Under extraordinary conditions

–Metabolic organic acid production can increase

–Ketoacids

–Diabetes

–Production of CO2–Acid production

•Base–Few dietary or metabolic sources of bases

Front 38

pH Homeostasis

Back 38

•Buffers

–Moderate changes in pH

–Combine with or release H+

–Cellular proteins, phosphate ions, hemoglobin, bicarbonate

•Ventilation

–Rapid response

–Corrects 75% of disturbances; can also cause them

•Renal regulation

–Receptor

-mediated endocytosis

–Directly by excreting or reabsorbing H+ Indirectly by changing in the rate at which HCO3– buffer is reabsorbed or excreted

Front 39

Renal Compensation: Transporters

Back 39

•Apical Na+-H+exchanger (NHE) –more in PT

•Basolateral Na+-HCO3=symport

•H+-ATPase = More DT and CD

•H+K+-ATPase = More DT and CD

Front 40

pH homeostasis along tubule

Back 40

•PT

–H+ is secreted across the luminal membrane via secondary active transport in exchange for Na+

•DT–small amounts of Na left in the filtrate. H+ secreted across the luminal membrane by primary active transport

•Both tubules

–HCO3- reabsorbed across the

basolateral membrane by some mediated mechanism

Front 41

Acid base Homeostasis

Back 41

•If the blood is acidic, the urine will be acidic

–Tubules secrete more H+ and reabsorb more HCO3-

•If the blood is basic, the urine will be less acidic)

–Tubules reabsorb less HCO3-(andsome cells secrete HCO3-), secrete lessH+

Front 42

Wall of the gut

Back 42

•Mucosa (inner most layer)

–Created from epithelial cells, lamina propria, and muscularis mucosae

–Modifications increase surface area

–Rugae and plicae

–Villi (only in small intestine)

–Gastric glands, crypts, and submucosal glands (both small and large intestine)

–Peyer’s patches of the gut

-associated lymphoid tissues (GALT)

Front 43

Wall of the gut

Back 43

•Submucosa (regulates sectretion)

–Connective tissue (most of it)

–Contains submucosal plexus of the enteric nervous system

•Muscularis externa (source of motility, moving mucosa around)

–Consists of two layers of smooth muscle (circular"makes is smaller" and longitudinal layer "makes it shorter")

–Contains myenteric plexus of the enteric nervous system

•Serosa

–Continuation of the peritoneal membrane, which forms sheets of mesentery

Front 44

Four processes of the Digestive system

Back 44

Digestion: chemical and mechanical breakdown of food into absorbable units. breaking bonds

Absorption: movemnt of material from GI lumen to ECF ( stomach to blood) not regulated, responds to other three processes

Motility: movement of material through GI tract as a result of muscle contraction

Secretion: movement of material from cells into lumen of ECF

Hint 44

Front 45

Motility

Back 45

•Slow

-wave potentials

–Originate in interstitial cells of Cajal (pacemaker type cells) if its below threshold, everything is relaxed

–Intrinsic activity that is modulated by presence of

food, ANS, hormones (food activates everything)

•Peristalsis (mainly in large intestine)

–Wave like contractions that move chyme forward.

–Found throughout the GI tract.

•Segmentation (mainly in small intestine)

–Several ring like contractions along the gut

–Promotes mixing and absorption

–Major motility in small intestine

Front 46

Polarizations of GI tract

Back 46

Front 47

types of segmented movement

peristalsis and segmentation hpic

Back 47

Hint 47

Front 48

Autonomic nervous system

Back 48

•Sympathetic nervous system (SNS) (inhibit everything, secretions, bloodflow)

–Postganglion neurons release NE

–Tends to inhibit digestive activity

•Parasympathetic nervous system (PNS or VAGUS)

–Postganglionic neurons release acetylcholine

–Tends to stimulate digestive activity

–Mostly vagus controls but sacral nerves control lower GI tract

•Enteric nervous system (ENS) lots of intrinsic neurons, regulated by extrinsic neurons

–Can serve as a control center for local reflexes

Front 49

ENS Shares Features with CNS

Back 49

•Intrinsic neurons

–As many neurons in ENS as in spinal cord

–Modulation by Extrinsic neurons (autonomic neurons) that bring signals from CNS to digestive system

•Neurotransmitters and neuromodulators

•Acetylcholine and serotonin are major neurotransmitters

•Glial support cells

•Diffusion barrier

•Integrating center

–Minibrain of the GUT

Front 50

Endocrine Secretion -Digestive Hormones

Back 50

•Gastrin family

–Gastrin and cholecystokinin (CCK)

•Secretin family

–Secretin, vasoactive intestinal peptide (VIP), glucose-dependent insulinotropic peptide (GIP), and glucagon-like peptide-1 (GLP-1)

•Others

–Motilin

all found in CT.11.3 use table 21.1 to fill it slide15

Front 51

Exocrine Secretion

Back 51

•Digestive enzymes secreted into mouth, stomach, and intestine

•Mucous cells in stomach, serous cells in salivary glands, and goblet cells in intestine

–Mucins

•Saliva is an exocrine secretion

•Liver hepatocytes secrete bile

–Bile salts, bile pigments, and cholesterol

–Gallbladder stores and concentrates

–Hepatic duct and common bile duct

Front 52

Wrapping up digestion

Back 52

-GI is big long tube, exocrine secretions are brough to the gut (like saliva) secretions from the liver and pancreas, like bile and other enzymes.

-pacemaker cells (interstitial cells of Ga-kal?)

-in order, Cephalic system (feedforward) when you smell --> Gastric phase --> intestinal phase (feedback) ---> integration

Front 53

The Cephalic Phase

Back 53

•Chemical and mechanical digestion begins in the

mouth

•Salivary secretion is under autonomic control

–Softens and lubricates food

–Chemical digestion: salivary amylase and some

lipase

–Saliva also has a protective function, antibacterial

•Chewing: mastication

Front 54

Sensory system

Back 54

Cephalic phase: see food -> medulla oblongata -> parasympathetic neuron in vagus nerve -> enteric plexus ->postganglionic parasympathetic and intrinsic enteric neurons

Gastric phase: secretion of saliva and movement of food towards stomach all sympathetic neuron controlled

Front 55

Back 55

1.Tongue pushes bolus against soft palate and back of mouth, triggering swallowing reflex.

•Starts voluntary

•Converts to a reflex

2.Breathing is inhibited as the bolus passes the closed airway.

3.Food moves downward into the esophagus, propelled by peristaltic waves and aided by gravity

Hint 55

Swallowing is integrated in the medulla oblongata. Sensory afferents in cranial nerve IX and somatic motor and autonomic neurons mediate the reflex.

Has to be a long reflex with the CNS as a control center because

Front 56

Esophagus

Back 56

-upper esophageal sphincter opens with swallowing

-upper third of muscularis is skeletal muscle and transitions to smooth muscle

-if bolus of food is stuck, local reflexes continue peristalsis

-lower esophageal sphincter is below the diaphragm (positive pressure of abdomen keeps closed, and reflux can occur if LES is pushed into thorax)

Front 57

Gastric phase

Back 57

Three functions of stomach: (storage: stomach)( digestion: stom.... unfinished

Front 58

Gastric glands in the gastric mucosa contains cells that secrete hnotes

Back 58

•HCl –part of barrier defense

•Pepsinogen ->Pepsin

–secreted first as a ZYMOGEN

–Activated by HCl in the lumen of the stomach.

Why is this protective? (you dont want to digest yourown cells, just the food) enzyme waits until it reaches the food until it activates

•Mucus

–protective layer

–Depends on prostaglandins and good blood flow

•Intrinsic factor-helps absorb Vitamin B12

•Gastrin: made by G-cells, puts gastrin into the blood, excitatory hormone, activates the gastric system

Hint 58

pepsin is what actually digests the food, HCl is what activates the pepsinogen to turn into pepsin

Front 59

Acid secretion regulators

Back 59

•Proton pumps are not always in the plasma membrane. Inserted with the appropriate stimulus

•Gastrin

•Vagal stimulation

•Acetylcholine

•Histamine

•Inhibited by somatostatin

Front 60

Acid secretion regulated by negative feedback

Back 60

•Food in stomach increases pH

–Stimulates ENS->ACH, gastrin, histamine ->increases acid secretion

•Emptying decreases pH

–Stimulates somatostatin

->inhibits acid, gastrin

and histamine

Front 61

Gastric emptying

Back 61

Gastric emptying

•Pacemakers in upper gastric muscularis start peristalsis

•Wave of contraction builds as it travels along the muscularis (starts w/ little depolarizations, then builds till its a giant contraction that shuts pyloric sphincter)

•Pylorus contracts and allows no more than a couple of tablespoons of chyme to enter the SI

•Gastric contents forced up away from pylorus to churn for awhile

•Allows the SI time to process the small amount just emptied

Front 62

structure of the small intestine

(short reflex, enteric nervous system)

Back 62

Hint 62

Front 63

The Intestinal Phase Secretions

Back 63

•Bicarbonate neutralizes gastric acid

•Goblet cells secrete mucus for protection and lubrication from acid

•Bile from the gallbladder(made from liver) for fat emulsion

•Digestive enzymes (pepsinogen, mucus, bicarbonate acid, intrinsic factor)

–From pancreas –amylase, protease (zymogens),

lipase, nuclease

–Brush border enzymes(made of microvilli)–lactase, Enteropeptidase

Front 64

THE VILLUS AND A CRYPT IN THE SMALL INTESTINE

Back 64

the crypt is going to secrete saline solution that liquifies the contents of small intestine, also crypt secretes hormones, CCK, secretin, motillin.

Villus: secretes mucus and absorbs fluids and nutrients.

countercurrent for oxygen exists here.

Hint 64

Front 65

exocrine vs endocrine secretions

Back 65

exocrine: mucus

endocrine: gastrin

Front 66

Digestion and Absorption

Back 66

Digestion and Absorption

•Nucleic acids (DNA and RNA)

are digested into nitrogenous bases and monosaccharides

•Intestine absorbs vitamins and minerals

–Fat-soluble vitamins are absorbed with fats

–Water-soluble vitamins are absorbed by mediated transport

–Vitamin B12 is absorbed when complexed to intrinsic factor and absorbed in the ileum

–Mineral absorption usually occurs by active transport

–Iron and calcium absorption is actively regulated

–Sodium is absorbed by enterocytes and colonocytes

Front 67

Absorption Review

Back 67

•Glucose

–taken up by secondary active transport into cell ->facilitated diffusion basolateral side ->into blood

•Amino acids

–luminal side by secondary active-> basolateral side by facilitated diffusion ->into blood

•Triglycerides

–luminal side by

diffusion-> basolateral side via

chylomicrons->into lymph

Front 68

Motility

Back 68

•Slow-wave potentials (electrical event)

–Originate in interstitial cells of

Cajal

–Intrinsic activity that is modulated by presence of

food, ANS, hormones

•Peristalsis

–Wave like contractions that move chyme forward.

–Found throughout the GI tract.

•Segmentation

–Several ring like contractions along the gut

–Promotes mixing and absorption

–Major motility in small intestine

•Motilin and migrating myoelectric complex (happens when nothing is there..) moves residual food through the intestine

Front 69

Pancreatic secretions

Back 69

•Pancreatic acini secrete digestive enzymes (regulated by CCK) and bicarbonate (regulated by secretin) this all regulates small intestinal mucosa, because thats where the food is located and where the stimulus is.

•Fatty acids and amino acids in duodenum-> plasma CCK ->enzyme rich pancreatic secretion flow through the Sphincter of Oddi to the lumen to digest substrates.

•Acid in duodenum ->plasma secretin

->bicarbonate rich pancreatic secretions flow into lumen to neutralize acid.

Front 70

lumen of small intestine

Back 70

when we send enzymes into the gut (GI tract) interacts with zymogens. Trypsinogen makes trypsin go into gut and do stuff

Front 71

Bicarbonate secretion in the pancreas and duodenum

Back 71

Front 72

describe the use of bile

Back 72

Bile is a secretion, but it causes the breakdown of things that also make excretory products. bile emulsifies nutrients so that your pancreas can absorb it.