physio final

pain

renal functions

1\. regulate volume (can sense general decrease in volume of blood, right atrium)

2\. regulate osmolarity

3\. regulate pH (net result of metabolism is acid load)

4\. excrete metabolic waste (bilirubin -> jaundice, yellow urine, brown feces; breakdown of RBC)

5\. regulate ECF ions (Na+, Cl-, K+, HCO3-, Ca++, Mg++)

6\. secrete hormones

anatomy of kidney (macro)

diaphragm

kidney

ureter

bladder

urethra

anatomy of kidney (mid)

kidney

\- made of nephron

\- fat deposit

\- renal cortex (outside)

\- renal medulla (inside)

→ renal pelvis

→ ureter → urinary bladder

nephron diagram !

renal corpuscle

\- glomerulus (glomerular capillaries)

\- bowman’s space in bowman’s capsule (125 mL of plasma filtered into bowman’s space, reabsorbing 124 mL back; 1 mL goes towards bladder)

→

renal tubule

\- proximal tubule

\-- proximal convoluted tubule

\-- proximal straight tubule

\- loop of henle

\-- descending thin limb of henle’s loop

\-- ascending thin limb of henle’s loop

\-- thick ascending limb of henle’s loop (contains macula densa at end)

\- distal convoluted tubule

\- collecting duct system

\-- cortical collecting duct

\-- medullary collecting duct

→

renal pelvis

glomerular filtration rate

125 mL plasma / min is filtered

renal plasma flow

500 mL plasma/min

glomerular capillary beds

\- blood comes in through afferent arteriole

\- high pressure which pushes plasma out (leaky)

\- what doesn’t get filtered out through efferent arteriole

\- distal tubule sends chemical messengers that change input on front end

renal process (tubule is a mini digestive tract)

\- glucose usually reabsorbed

\- bilirubin and urea stay in lumen and get highly concentrated in urine

days filtered per min

first artificial organ to be produced (willem kolff artificial kidney)

\- takes blood out → push through tub of isotonic saline solution → bring blood back into body

\- sausage casings (act as thin layer of digestive tract) + simple diffusion

\- modernized versions = kidney dialysis (tube will allow blood + dialysis fluid going in opp. direction to diffuse through semi-permeable membrane)

review of important terms + stats in renal 1

\- renal blood flow (1000 mL/min)

\- renal plasma flow (500 mL/min … Ht?)

\- Glomerular Filtration Rate (GRF) (125 mL/min) AKA how much plasma is filtered every minute

\- reabsorption (125 mL/min)

\- secretion (solutes… affect concentration)

\- excretion (1 mL/min)

\- filtration fraction = GFR/RPF = 125/500 = 0.25

GFR regulation

\- proteins in plasma are not permeable, fewer proteins in filtrate that comes out → osmotic gradient that draws water in

\- hydrostatic pressure (high pressure b/c lots of filtration)

\- if minerals come out of solution and precipitate in renal pelvis → create a kidney stone (block ureter); pressure (Pfluid) will go higher than 15 mmHg

extracellular matrix

\- pressure in lumen of capillary drives filtration through slits between endothelial cells and podocytes

\- RBCs do not go through holes of capillaries

\- generally, protein should not be going through unless after intense exercise

\-- some physically quite large

\-- electrical force field preventing them from getting through

\-- negative charge in extracellular matrix negatively repels negatively charged proteins

resistance, pressure, flow in glomerulus (pt. 1)

resistance, pressure, flow in glomerulus (pt. 2)

\- Raff = Reff

\- pressure proportional to resistance

important table of resistance, pressure, blood flow, and filtration fraction

regulation of GFR: regulation of pressure in glomerular capillaries (sympathetic stimulation)

moderate to high - constriction of aff and eff arteriole

severe - even greater constriction of aff arteriole

regulation of GFR: regulation of pressure in glomerular capillaries (autoregulation)

myogenic response (renal baroreceptor within kidney) (stretch → increase in \[Ca++\] in)

juxtaglomerular apparatus

\- macula densa cells

1\. release paracrine factors (aff arteriole)

\- increase NaCl → purines (e.g. adenosine) → constr.

\- decrease NaCl → Nitric Oxide → dilation

2\. release paracrines that release Renin from Juxtaglomerular Cells. Renin activates hormones in blood (see endocrine)

regulation of GFR: regulation of pressure in glomerular capillaries (endocrine short story)

NaCl in distal tubule → paracrines from macula densa → renin from juxtaglomerular cells → Angiotensin II in blood → constriction of aff and eff arteriole (and many other effects throughout body)

stuff that goes into capillary

\

transport solutes across and water follows… it’s osmotic gradient

\- into capillary from tubular

flow through tubule (H2O + Glucose)

transport max

sodium reabsorption

\- water follows (except for thick ascending)

\- thick ascending reabsorption of Na+ sets up osmotic gradient that results in more water reabsorbed (discussed later)

\
\- proximal tubule (65-80%)

\- descending loop (no but sets up gradient)

\- thick ascending loop (10-20%)

\- distal tubule (5-10%)

\- collecting duct (3-5%)

flow through tubule (sodium, potassium, insulin, PAH)

\

flow rate of glucose, insulin and PAH through blood, filtrate

\- renal plasma flow is 400 mL plasma/min

\- concentration of glucose, insulin, and PAH are all 1.00 mg/mL

\- flow rate for glucose, insulin, and PAH is 500 mg/min (=RPF x \[solute\]plasma)

\- GFR = 125 mL/min so filtration rate for all is 125 mg/min

\- glucose is reabsorbed so reabsorption is 125 mg/min and excretion is 0 mg/min

\- insulin is not reabsorbed or secreted so reabsorption is 0 and excretion is 125

\- PAH is not reabsorbed and remaining PAH in blood is actively secreted (275 mg/min) so excretion is 500 mg/min

clearance + calculations

amount of blood plasma that is 100% cleared of a solute (mL/min)

\
\- Cx = ml plasma/min

\- Vdot = urine flow rate (ml/min)

more calculations for plasma x Clearance

RPF = CPAH/0.91

\- not all of the plasma going to the kidney is cleared of PAH

free water clearance

1\. zero free water clearance (urine and plasma concentration equal)

2\. positive free water clearance (dilute urine; more dilute than plasma)

3\. negative free water clearance (concentrated urine; more concentrated than plasma)

ADH (antidiuretic hormone)

\- “against water loss”

\- vasopressin

\
release triggered by

\- increased osmolarity

\- decreased plasma volume

ADH flowchart

\- excess h2o ingested

\- decreased body fluid osmolarity (increase h2o concentration)

\- decreased firing by hypothalamic osmoreceptors

\- in posterior pituitary: decreased vasopressin secretion

\- decreased plasma vasoprssin

\- in collecting ducts: decreased tubular permeability to h2o, decreased h2o reabsorption

\- increased h2o excretion

how is vertical osmotic gradient established?

KEY = thick ascending limb

1\. thick ascending limb of loop of henle

to make filtrate more dilute and concentrate interstitial fluid

\- Na/K/2Cl pump (active transport out of filtrate into interstitial fluid)

\- impermeable to H2O so filtrate gets dilute and interstitial fluid gets concentrated

\
2\. loop of henle and vasa recta

multiply this effect to create a large standing vertical osmotic gradient in renal medulla

\- ascending limb activity concentrates filtrate in descending limb

\- higher concentration of Na, K, and Cl increases flux of these ions in thick ascending limb

\- direction of loop and transport generates and maintains vertical gradient

\
3\. ADH allows urea to be more permeable in lower renal medulla. adding another solute increases the concentration

vasa recta facilitates distribution

\- distribute osmolarity so ascending limb affects filtrate in descending limb

\- delivers blood to renal medulla without “rinsing out” the osmotic gradient (blood flow goes down from cortex and back up to cortex normalizing concentration)

another way of looking at osmotic gradient

1\. turn on nephron transport in ascending limb

2\. start the countercurrent flow

urea in establishing vertical osmotic gradient

\- ADH increases permeability of urea in collecting duct and loop of henle at hte very lower end of the renal medulla

\- some urea is kept inside kidney to further concentrate extracellular fluid

figures w/ vasopressin

\- only will see 1200 if ADH is very high

ADH second messenger system

\- inserts existing proteins (aquaporin-2) into the apical membrane of endothelial cells in collecting duct

\- existing osmotic gradient draws water back into the body

\- fast to turn on and fast to turn off as it inserts or removes proteins that already exist

ADH effects on water reabsorption in kidney

\- ADH caused insertion of aquaporin channels into cells of the collecting duct (reabsorb more water)

\- ADH increases osmotic gradient in renal medulla

\- ADH is also secreted in response to low blood pressure in systemic arteries and atria (to get volume back into body to increase MCFP)

concentration in renal medulla interstitium with/without ADH

concentration of filtrate of nephron with/without ADH

increased ADH + flow chart

\- increased osmolarity

\- decreased plasma volume

what primarily regulates blood volume (isosmotic gain or loss)

renin/angiotensin/aldosterone

and

atrial natriuretic peptide (ANP)

3 stimuli that affects juxtaglomerular cells + flowchart

1\. sympathetic neurons

2\. change in renal blood pressure (renal pressure sensation)

3\. flow of chloride in distal tubule affecting macula densa cells which regulate renin release from juxtablomerular cells

increased plasma volume

\- increased sodium excretion

liver and blood pressure flowchart

aldosterone acts through regulation of transcription

\- system is slow to turn on and slow to turn off as it depends on changing levels of protein synthesis

atrial natriueretic flowchart

handling of a salt load

\- ADH first (fast) and RAAS second (slower)

\- ingest NaCl and osmolarity increases

\- osmoreceptors stimulate

\~ release of ADH

\~ thirst

\- water is ingested and retained to return osmolarity to setpoint within minutes

\- higher volume is sensed by low pressure volume receptors which

\- decrease RAAS

\- increase ANP

\- isosmotic loss of NACl and water to return volume to setpoint

cardiovascular + renal flowchart

\- dehydration involves BOTH loss of volume and increase in osmolarity

\- cause low volume/low blood pressure response and high osmolarity responses

\- blue dashed lines are increased osmolarity directly inhibiting the release of aldosterone from the adrenal cortex. while angiotensin II is trying to stimulate release of aldosterone, increased osmolarity counters this stimulus. the downstream effect of this battle is decreased aldosterone (rather than decrease)

acid/base balance - respiratory acidosis

\- Vco2/VA larger value

\- hypoventilation

acid/base balance - respiratory alkalosis

\- Vco2/VA smaller value

\- hyperventilation

acid/base balance - metabolic acidosis

\- lactic acid

\- metabolic state (ketones)

\- kidney failure (daily acid load)

\- “deep vomiting” (basic solution out of mouth - small intestine)

acid/base balance - metabolic alkalosis

\- vomiting

\- excess antacids

\- hyperaldosteronism (more Na+/H+ exchange)

\- retention of bicarbonate

buffer systems in the body

extracellular - carbonic acid/bicarbonate

intracellular and some extra. - protein

RBC - hemoglobin

urine and intracellular - phosphate

respiratory system’s ability to regulate H+ (and HCO3-)

\- respiratory compensation for high \[H+\] so plasma \[H+\] is x and ventilation is y

\- VCO2 constant

\- as plasma \[H+\] increases, minute ventilation increases to compensate (not the other way around)

kidney’s ability to regulate H+ (acid) and HCO3- (base) reabsorption and secretion

\- greater ability to excrete acid built into renal mechanisms bc daily acid load

\
\- proximal tubule

1\. Na+ and HCO3- (IN) → reabsorb base; use CA to accomplish this

2\. Glutamine (IN)

Na+ and HCO3- (IN) H+ (OUT) → base in, acid out

\- collecting duct

K+ and HCO3- (IN) H+ (OUT) → base in, acid out

OR

H+ (IN) K+ and HCO3- (OUT) → acid in, base out

reabsorption of acid and base flowchart

NA+ - H+ antiport secretes H+

H+ in filtrate combines with filtered HCO3- to form CO2

CO2 diffuses into cell and combines with water to form H+ and HCO3-

H+ is secreted again and excreted

HCO3- is reabsorbed

Glutamine is metabolized to ammonium and HCO3-

NH4+ is secreted and excreted

HCO3- is reabsorbed

intercalated cell function in acidosis and alkalosis

is h2co3 / hco3- a good buffer system for the body?

according to henderson hasselbach

\- ideal buffer exists when pK = desired pH

\-- 50% exists as base (proton acceptor) and 50% exists as acid (proton donor)

HH for carbonic acid

\[see image for equation\]

\- h2co3 = co2 due to presence of carbonic anhydrase

co2 = acid

\
CO2 + H2O

buffer system

\- much more base (20x) compared to acid

\- CO2 can be increased by changing respiration (alveolar ventilation) and can be trapped to add acid to body quickly

\- pH = pK then 50% exists as HCO3- and 50% exists as CO2 (pH = 6.1 and u would be dead)

\- pH = 7.4 then 95% exists as HCO3- and 5% exists as CO2 (good for accepting H+ but bad for donating H+)

disturbances in acid/base states and compensation

changes in pH caused by:

\- changes in ventilation (PaCO2) can be compensated for by changes in renal retention and excretion of acid and base

\- metabolic causes can be compensated for by changes in ventilation (PaCO2)

\
respiratory generated changes in pH are fast (sec), while renal generated changes take much more time (hours/days0

relationship of HCO3- and CO2 concentrations to pH in various acid/base statuses (pt 1)

relationship of HCO3- and CO2 concentrations to pH in various acid/base statuses (pt 2)

davenport plot

causes and compensations questions

1\. acidosis or alkalosis

2\. CO2 normal or not (if CO2 is normal then no respiratory compensation; all metabolic and uncompensated)

3\. if co2 is not normal is it a cause or compensation?

\-- CO2 high - consistent with acidosis so co2 is cause; if alkalosis, then high CO2 indicates compensation

\-- CO2 low - consistent with alkalosis so co2 is cause; if acidosis then low co2 indicates compensation

4\. hco3 differences are greater in compensated states

POWER

1 watt = 1 N-m/sec (1 m/s, 1 small apple)

work done by muscle = force x distance of contraction x number of contractions

power = work/time

muscle fiber type - slow twitch (ST)

slow fatigue-resistant → endurance

\- least powerful: 39 N/cm^2

\
\- less myosin, stained darker in the image in ppt

muscle fiber type - fast twitch a (FTa)

fast fatigue - resistant → intermediate

\- intermediate power

muscle fiber type - fast twitch b (FTb)

fast fatiguable → sprints

distribution of fiber types (within the same individual)

\- vastus lateralis

50% ST

35% FTa

15% FTb

\
\- soleus

85% ST

\
\- triceps brachii

30% ST

distribution of fiber types (between individuals)

\- great variability between individuals

\- mostly determined genetically

energy systems

\- source of atp for cross bridge formation

\
phosphagen system (10 sec)

\- stored ATP - 3 sec (4 moles ATP/min)

\- phosphocreatine - 7 sec

\
glycolytic system (1-2 min)

\- glycolysis (2 moles ATP/min)

\- inefficient but fast

\- buildup of lactic acid - must be buffered

\
oxydative (aerobic) (indefinite)

\- very efficient (carbs - 1 mole ATP/min)

\- slow release of ATP (fats - 0.8 moles ATP/min)

\- fatigue resistance

fiber type recruitment order

1\. slow-twitch (aerobic)

2\. fast-twitch a (aerobic/anaerobic)

3\. fast-twitch b (anaerobic)

old story - anaerobic threshold

as exercise intensity increases

\- oxygen levels are insufficient to support aerobic pathways

\- pyruvate accumulates in cytosol forcing anaerobic metabolism

\- lactate accumulates as “waste product” and enters blood

\- buffering of lactate by HCO3- results in increased VCO2

\- VE increases disproportionately to VO2 due to decreased pH and increased VCO2

\
FALSEEEEEEE

\- pyruvate is not just a ‘waste product’ but a resource that is used as fuel (glucose in liver) and signaling molecule

new story - anaerobic threshold

as exercise intensity (VO2 proportional to power) increases

\- VE increases (disproportionate increase at AT)

\- lactate appears in blood

\- pH decreases

\- PCO2 decreases

problems with anoxia triggering lactate increase in blood

\- PO2 does not drop to 2 mmHg which is theoretical limit at which aerobic pathways experience oxygen deficit

\- lactate is used to shuttle important molecules into and out of muscle cells

\- lactate is removed from the blood and “consumed” by other cells

\- trained athletes demonstrate a transient increase in lactate at their AT that diminishes over time

\
at very intense levels of exercise, above AT, anoxia still plays a role

lactate threshold is still important measure for athletic training

percentage of CHO and fat vs exercise intensity

\- absolute level of energy usage increases with intensity

\
why the shift from fat to CHO?

1\. slow twitch fibers switch from fat to carbs to generate more power

2\. recruitment of fast twitch muscle fibers which use glycolysis exclusively

glycogen depletion

\- fast twitch a and b

glycogen restoration v. diet

\

oxygen and fuel

oxygen - from blood, stored bound to myoglobin

fuel = glucose - from blood (liver make it from glycogen), stored in muscle (glycogen), fast delivery rate

excess post-exercise oxygen consumption (EPOC - increase mL O2/min aka increase VO2)

\- rapid component

\- prolonged component

\- magnitude

\~ measured as area under curve

\~ prolonged greater than Rapid

\~ magnitude depends on intensity and duration of exercise

fatigue

energy depletion

\- phosphocreatine (short, hard efforts)

\- glycogen depletion (longer efforts)

\
buildup of metabolic byproducts

\- lactic acid (current research does not support this as having a direct effect on weakening muscle contraction)

\- electrolyte changes (intracellular or extracellular)

\~ increase in extracellular K+?

\~ depolarization of Vm of muscle cells

\~ less release of Ca++ from sarcoplasmic reticulum

\
nervous system

\- physiological (spinal cord reflexes) and psychological)

endurance training

\- increased vascularization - more capillaries

\- increased myoglobin

\- more mitochondria

\- more oxydative enzymes

\- improved fat metabolism

anaerobic training (increase anaerobic threshold and increase anaerobic capacity)

\- more glycolytic enzymes

\- more glycogen stored

\- increased capacity to utilize lactate

\~ less release from active muscle at given power

\~ more uptake by other cells - lactate shuttling (e.g. some muscle metabolizes lactate; liver makes glucose from lactate)

\- psychological training AKA deal with pain

muscle cramps

cause?

\- overuse, muscle strain, holding the same position (prolonged contraction)

\- K+, Mg++, or Ca++ deficiency

\- dehydration

\- symptoms of underlying conditions (nerve compression; inadequate blood supply)

\
many theories but in most cases the cause of muscle cramps is unknown

\- recent theory implicates sensory nerve endings in muscle that are excited when muscle is fatigued or overused resulting in a spinal cord reflex which activates motor neurons going to the same muscle

\~ in experimental animals, blocking the sensory axons coming out of a muscle or motor axons going into a muscle decreases cramping significantly

primary structures of GI (food passes through)

mouth

pharynx

esophagus

stomach

small intestine

large intestine

rectum

auxiliary structures (connected via duct)

salivary glands

liver and gall bladder

pancreas

GI parts

pharyngoesophageal

gastroesophageal

pyloric

illeocecal

internal anal sphincter

\- smooth muscle

external anal sphincter

\- striated muscle

protection of GI

turn on only when food is present

compartmentalization

\- COMMUNICATION

1\. neural

2\. hormonal

secrete precursors

mucous barrier

high turnover rate of epithelial cells lining the GI tract

nutrients

carbs

\- polysaccharides (sucrose, lactose, fiber)

\- mono (glucose, galactose, fructose)

\
proteins

\- polypeptides → peptide fragments → amino acids

\
fats

\- triglyceride → monoglyceride + free fatty acids

\
vitamins, minerals, water, etc.

GI secretions + absorptions

anatomy of gut: stomach and intestine

nervous control

\- sympathetic and parasympathetic axons primarily innervate ENS neurons

\- sometimes can directly innervate smooth muscle and secretory cells

\- gut has taste receptors LOL?

nucleus of the solitary tract

\- major integration center for feeding in brainstem

NOS

\- receives visceral sensory and somatic sensory input

\- coordinates visceral motor reflexes

\- affects hypothalamus and release of hormones

\- affects behavior associated with feeding

\- in medulla

stomach parts

stomach parts + substance secreted + stimulus for release + function

secretion of HCl