Renal Physl Flashcards
where are the kidneys located?
behind abdomen/peritoneum on either side of the spine
where are the adrenal glands located?
above each kidney
kidneys are supplied w/ a _______________ bundle
neurovascular (renal veins, arteries, lymphatics, nerves, and a ureter)
what drains urine from the kidneys to the bladder?
ureters
what are differences btwn urethral position in males vs females?
males: urethra passes through prostate and penile shaft
females: shorter (incr risk for UTIs)
what is the renal hilum?
point of entry/exit of renal arteries, veins, lymphatics, nerves, and ureter (neurovascular bundle)
what is the form and function of the renal capsule?
tough, fibrous layer around kidney for protection and hemodynamics (BF)
what are the 2 sections of the kidney?
cortex (periphery) and medulla (center)
what does the medulla of the kidney feature?
renal pyramids (-> renal papillae project into renal pelvis/upper ureter)
what is at the point facing the center of renal pyramids?
renal papillae
what do renal papillae project into?
renal pelvis ie. upper ureter
what do renal papillae drain into?
minor and major calyces
t/f: calyces, renal pelvis and ureters contains contractile elements
true
t/f: kidneys do not receive a significant proportion of cardiac output
fasle, receive almost 22% of CO (significant)
what does the renal artery progressively branch into? (4)
interlobar arteries, arcuate arteries, interlobular arteries, afferent arterioles
what do afferent arterioles give rise to?
glomerular capillaries
what do glomerular capillaries coalesce to form?
efferent arterioles
what do efferent arterioles branch to form?
peritubular capillaries
what do peritubular capillaries drain to form? (4)
interlobular veins, arcuate veins, interlobar veins, renal vein
approx. how many nephrons are in each kidney?
~1 million
what % nephrons are cortical vs juxtamedullary?
cortical: 80% (in cortex)
juxtamedullary: 20% (in medulla)
what surrounds the renal tubules?
peritubular capillaries
what are longer, specialized peritubular capillaries that surround juxtamedullary nephrons?
vasa recta
what is the different shape btwn cortical vs juxtamedullary nephrons?
cortical: rounder/tangled
juxtamedullary: longer/skinner (down and back)
what does Bowman’s capsule surround?
glomerular capillary tuft (epithelium fused w/ endothelium of glomerular capillaries)
what is Bowman’s Capsule + glomerulus sometimes called?
renal corpuscle
what does filtrate from glomerular capillaries drain into? (2)
Bowman’s capsule and tubular portions of nephron
what are 4 segments of the renal tubule in order?
proximal tubule, loop of henle, distal tubule, collecting duct (to renal pelvis, ureter, bladder, urethra)
where does the loop of henle dip towards/within?
renal medulla
what does the collecting duct do?
merges >1 distal tubule from diff nephrons
what is the juxtaglomerular apparatus?
distal/ascending tubule passing btwn afferent and efferent arterioles within the glomerulus
what forms the renal tubular walls?
tubular epithelium cells (connected by tight junctions)
what do the apical vs basolateral surfaces of tubular epi cells face?
apical: tubular lumen
basolateral: renal interstitium
what feature does the apical side of tubular epi cells have?
microvilli (incr absorption)
what does the basolateral side of tubular epi cells rest on?
basement memb
what is the renal interstitium?
space btwn nephron and peritubular capillaries
what are the 3 basic renal processes?
glomerular filtration, tubular reabsorption, and tubular secretion
what is (usually) unable to cross the glomerular capillary wall into Bowman’s capsule?
proteins
what are 3 functions of renal processes?
remove metabolic wastes, maintain H20 V, stabilize blood V and P
what is reabsorption vs secretion?
reabsorption: filtrate moves from tubular lumen to circulation via peritubular cap. or vasa recta
secretion: solutes move from circulation into tubular filtrate for excretion
why is reabsorption important?
conserves essential substances (water, salt, glucose)
why is secretion important?
incr removal of metabolic wastes
what is filtrate composition similar to? tonicity?
plasma; isosmotic
where is 70% of filtrate V reabsorbed?
proximal tubule (before loop of henle)
how are solutes vs water reabsorbed in proximal tubule?
solutes: actively reabsorbed
water: follows solutes by osmosis (filtrate is dilute)
how is filtrate kept isosmotic?
osmosis balances [water] in and out of tubule based on solute movement/conc
what do the descending vs ascending loop og henle reabsorb?
desc: h20 reabsorption (impermeable to solute)
asc: solute (impermeable to h20)
what is the tonicity of filtrate leaving loop of henle?
hypotonic (dilute)
what is a feature of the distal tubule and collecting duct?
sensitive to hormones for salt and h20 regulation based on body’s needs
at what point is filtrate destined for excretion?
renal pelvis
what is amount of solute excreted =?
amount excreted = amount filtered - amount reabsorbed + amount secreted
what % of plasma is filtered out of glomerular capillaries at any time?
20%
what does remaining plasma/RBCs enter to return to systemic circulation?
peritubular capillaries
what is the proportion of plasma V that filters into tubule called?
filtration fraction
what are 3 filtration barriers in the renal corpuscle?
glomerular capillary endothelium, basal lamina (basement memb.), and Bowman’s capsule epithelium
what does the glomerular capillary endothelium feature that incr filtration?
fenestrated capillaries (large gaps btwn endo cells)
what do glomerular capillary fenestrae permit filtration of? (and not)
most solutes except plasma proteins and RBC’s
what is the charge on the glomerular capillary pore surface? why?
negative; repels neg charged plasma proteins (to stay in circ)
where is the glomerular basement memb/basal lamina?
ECM (acellular)
what does the glomerular basement memb/basal lamina separate?
glomerular capillary endothelium and Bowman’s epithelium
what is the charge on the glomerular basement memb/basal lamina? why?
negative (glycoproteins and collagen); repel plasma proteins
what are the Bowman’s epithelium cells closest to glomerular capillaries called?
podocytes
what are 3 features of podocytes?
wrap around glomerular capillaries, have foot processes, and slits for filtration
what cells in Bowman’s capsule epi are contractile?
mesangial cells (btwn and around glomerular capillaries)
what do mesangial cells contribute to?
capillary blood flow (contract)
what does glomerular capillary hydrostatic P favour?
filtration (outwards F on walls)
what 3 starling forces dictate glomerular filtration?
capillary hydrostatic P, capillary colloid osmotic P, Bowman’s capsule hydrostatic P (Bowman’s capsule colloid osmotic P negligible)
what is greater: capillary hydrostatic P or Bowman’s capsule hydrostatic P? result?
capillary hydrostatic P; NET filtration
what causes capillary colloid osmotic P?
proteins in capillaries (opposes filtration/favours absorption)
what is greater: capillary hydrostatic P or capillary colloid osmotic P? result?
capillary hydrostatic P; NET filtration
what is GFR?
V of fluid entering Bowman’s capsule/time
what is GFR influenced by? (2)
net filtration P and filtration coefficient (Kf)
what is net filtration P affected by?
renal blood flow (RBF) and BP (∝ filt P ∝ GFR)
what is the filtration coefficient? (2)
total SA for filtration (glomerular capillaries) and permeability of barrier btwn capillaries and Bowman’s capsule (∝ Kf ∝ GFR)
if filtration P or Kf decr, what occurs to GFR?
decr (proportional)
renal ______________ nerves innervate vasculature and tubules of kidney
sympathetic (ANS)
what does incr sympathetic renal nerve activity cause? (3)
vasoconstriction, decr RBF, decr GFR
how do RBF and GFR remain stable in arterial BP fluctuations?
via renal autoregulatory mechanisms
what are 2 mechanisms of renal autoregulation?
myogenic response and tubuloglomerular feedback mechanism (TGF)
btwn what BP do renal autoregulatory mechanisms work to stabilize RBF and GFR?
80-180 mmHg
what occurs to RBF and GFR at arterial BPs <80 mmHg and >180 mmHg?
<80: RBF and GFR decr
>180: RBF and GFR incr
what is the renal myogenic response?
changes in BP and RBF can alter vascular smooth muscle contraction/relaxation in glomerular afferent arterioles
if BP and RBF incr, what occurs in glomerular afferent arterioles from the myogenic response? (6)
walls of glomerular afferent arterioles stretch, stretch-sensitive ion channels open, muscle cell depolarizes, V-gated Ca channels open, vasoconstriction, downstream RBF, BP, and GFR decr (return to normal)
what would myogenic response in glomerular efferent arterioles cause? (constriction vs relaxation)
constriction: incr glomerular hydrostatic P and GFR
relaxation: no incr in glomerular hydrostatic P or GFR
what is tubuloglomerular feedback?
modulation of RBF and GFR based on rate of tubular fluid flow
what are specialized cells in the early distal tubule at the juxtaglomerular apparatus called?
macula densa cells (in tubule walls)
what are macula densa cells in the juxtaglomerular apparatus in contact with?
juxtaglomerular/granular cells in wall of glomerular afferent arteriole
what do juxtaglomerular/granular cells in the wall of glomerular afferent arterioles secrete?
renin
if RBF and GFR incr, what occurs at the juxtaglomerular apparatus from the tubuloglomerular feedback mechanism? (7)
incr flow past macula densa in distal tubule, release paracrine factor, afferent arterioles constrict, incr R, decr RBF, decr glomerular hydrostatic P, decr GFR (back to normal)
if RBF and GFR decr, what is the tubuloglomerular feedback mechanism to regulate this? (6)
decr flow past macula densa, incr renin secretion from juxtaglomerular/granular cells in aff arteriole, incr angiotensin 2, efferent arteriole vasoconstriction, incr P, incr RBF and GFR (back to normal)
what % of filtered fluid is reabsorbed?
99% (1.5L of urine produced)
why is substantial filtration necessary? (2)
incr removal of wastes and controls fluid and electrolyte balance
how are Na ions moved from tubular lumen to interstitium in proximal tubule?
active transport via basolateral Na/K ATPase
what is the purpose of the basolateral Na/K ATPase in proximal tubule?
maintains low [Na] in epi cell so Na can flow down conc gradient from lumen
what 2 proteins facilitate Na reabsorption on the apical side of tubular epi cells?
Na/H exchanger (NHE) and epi Na channels (ENaC) - both passive transport
what occurs when Na ions are actively transported across tubular epi? (6)
creates transepi concentration and electrochemical gradient, anions flow out (follow Na+), tubular filtrate diluted, water follows by osmosis, filtrate concentrated, remaining solutes (K, Ca, urea) exit down conc grad
what is the difference btwn trans and paracellular transport?
transcell: through epi cells
paracell: diffusion btwn epi cells
how is glucose moved across the tubular epi cell?
Na moves down conc grad on apical side and brings glucose w/ it up conc grad (secondary active transport)
how is urea moved across the tubular epi cell?
passive reabsorption by trans/paracell transport after Na and water reabsorption (filtrate is concentrated)
how are proteins that do end up entering the tubule lumen conserved? (2)
receptor-mediated endocytosis and breakdown to aa by lysosomes (apical to baso to interstitium to cap)
when does saturation of renal transport occur and effect? ex?
all available transporters are occupied, excess solute is not reabsorbed and is excreted; diabetes (max. occupied SGLT)
what forces allow reabsorption of water and solutes from the interstitium to peritubular capillaries?
Starling Fs
how do starling Fs favour absorption of fluid/solute from interstitium to peritubular capillaries?
low peritubular cap hydrostatic P (Pout) and high cap colloid osmotic P (Pin)
what is the process of renal secretion?
movement of substances from capillaries to renal interstitium to lumen for excretion (by memb transporters)
what are 2 reasons for renal secretion?
facilitates ion balance and incr excretion of wastes
t/f: renal secretion is a passive process (down grad)
false, renal secretion is an active process (against grad)
what are OATs?
organic anion transporters
what do OATs move?
variety of OA-/wastes (bile salts, chemicals, drugs) into epi cells (up grad)
what side of tubule epi cells are OATs on? why?
basolateral; facilitates OA- secretion/excretion
what does renal excretion depend on? (3)
filtration rate, reabsorption, secretion
what can renal clearance help estimate?
GFR (assesses renal function)
what is renal clearance?
rate substances are lost from body by excretion/metabolism or V of plasma cleared of a substance per min
what is clearance rate (mL/min) =?
clearance rate = [substance]urine (amount/mL urine) * urine flow rate (mL/min) / [substance]plasma (amount/mL plasma)
if a substance is freely filtered wo/ reabsorption/secretion, what is its clearance =?
GFR
what is an ex of a substance used to measure clearance/GFR? why?
inulin, 100% of filtered substance is excreted (not reabsorbed/secreted)
aside from inulin, what is used to measure clearance/GFR clinically?
creatinine (some is secreted but is endogenous to body vs inulin)
approx. how many mL of urine can the bladder hold?
500 mL
where are the internal and external urethral sphincters?
btwn bladder and urethra
what kind of muscle does the internal vs external urethral sphincter have?
internal: smooth muscle
external: skeletal muscle
what causes the internal vs external urethral sphincters to stay contracted?
internal: contraction at rest
external: contraction w/ constant CNS stimulation (unless urinating)
t/f: the internal urethral sphincter is part of the bladder wall
true
what kind of neurons control the external urethral sphincter?
somatic motor neurons
what is the micturition reflex? (7)
bladder fills w urine, stretch receptors fire, sensory neurons stimulate spine, parasymp neurons fire to contract bladder smooth muscle (at same time) motor neurons stop firing to relax external sphincter, internal sphincter is passively pulled open, urine expelled through urethra
what can facilitate/inhibit the micturition reflex?
higher brain centers (brain stem/cortex)
how do higher brain centers inhibit the micturition reflex?
override parasymp input to bladder and motor input to ext sphincter
what must fluid and electrolyte intake =?
output (for homeostasis)
what are examples of water intake (2) vs losses (4)?
intake: ingestion, intravenous
loss: sweating, feces, urine, insensible (skin diffusion/respiration)
what determines water ECF and plasma osmolarity?
water and sodium content
what can improper electrolyte levels lead to?
disruption to cellular processes and body pH, can be life-threatening
what is total body water divided into? (2)
ICF: intracellular fluid and ECF: extracellular fluid
what are the 2 locations of ECF?
interstitial fluid (IF) and plasma
does ICF vs ECF contribute more to total body water? and of ECF, IF vs plasma?
ICF > ECF of TBW
IF > plasma of ECF
what is the effect of cell membs being highly permeable to water?
fluctuations in ECF osmolarity effects cell V
what does high vs low ECF osmolarity mean?
high ECF osmolarity: hypertonic and cells shrink (lose water)
low ECF osmolarity: hypotonic and cells expand (gain water)
what 3 body systems control fluid and electrolyte balance?
cardiovascular, behavioural, renal (kidneys)
how do cardio, behavioural, and renal systems react to maintain fluid/electrolyte balance when blood V and BP decr? (5)
V receptors in atria and baroreceptors in carotid/aortic bodies trigger homeostatic reflexes, cardio incr output/vasoconstriction, behaviour incr thirst to incr ECF and ICF V, kidneys conserve water, BP incr
how do cardio and renal systems react to maintain fluid/electrolyte balance when blood V and BP incr? (4)
V receptors/endocrine cells in atria and baroreceptors in carotid/aortic bodies trigger homeostatic reflexes, cardio decr output/vasodilation, kidneys excrete water and salts to decr ECF and ICF V, BP decr
what controls short-term vs long-term BP?
ST: cardio system
LT: kidneys (water/salt balance ∞ blood V ∞ BP)
how many mLs of water are ingested from food or drinks/day?
2100 mL/day
how many mLs of water are produced in metabolism/day?
200-300mL/day
what do the kidneys do when there is excess water vs dehydration?
excess water: produce large V of diluted urine
dehydrated: produce small V of conc urine
what hormone controls water balance?
vasopressin (antidiuretic hormone/ADH)
when is vasopressin/ADH released and what does it do?
low blood V/P or incr plasma osmolarity (hypertonic), incr renal water reabsorption by incr expression/insertion of aquaporins
where does vasopressin target?
distal tubule and collecting duct
what type of aquaporins mediate renal water reabsorption w/ vasopressin?
AQP2
where and how is AQP2 inserted?
apical and basolateral memb of distal tubule and collecting duct; exocytosis
where are AQP2s stored wo/ vasopressin?
intracellular storage vesicles
what receptor does vasopressin bind to for AQP2 release?
V2 (GPCR)
is vasopressin release more sensitive to high plasma osmolarity or decr blood V/P?
high plasma osmolarity
what detects high plasma osmolarity for vasopressin release?
hypothalamic osmoreceptors (firing rate incr w/ osmolarity)
what detects large decr in blood V/P for vasopressin release?
arterial baroreceptors (relays to hypothalamus)
what stimulates thirst (behavioural)?
hypothalamic osmoreceptors (when plasma osmolarity incr)
what prevents dehydration?
avoidance behaviour (sun)
what is reabsorbed in the proximal tubule and what is the osmolarity of the filtrate when leaving?
reabsorbed: water and salt
osmolarity: isosmotic
what is reabsorbed in the descending limb of the LoH and what is the osmolarity of the filtrate when leaving?
reabsorbed: water
osmolarity: hyperosmotic
what is reabsorbed in the ascending limb of the LoH and what is the osmolarity of the filtrate when leaving?
reabsorbed: solute
osmolarity: hypoosmotic
what is reabsorbed in distal tubule and collecting duct and what is the osmolarity of the filtrate when leaving?
reabsorbed: solute and water (variable)
osmolarity: depends on vasopressin release (incr water reabsorption w/ incr release)
what is the osmolarity of the renal cortex vs medulla?
cortex: low osmolarity (isosmotic w/ plasma)
medulla: high osmolarity
what is the countercurrent exchange in the vasa recta?
fluid flowing in LoH flows opposite to blood in vasa recta
what is the purpose of the countercurrent exchange in the vasa recta?
preserves high renal medulla osmolarity by reabsorbing water and salt removed from LoH
What can excess sodium cause? (4)
Incr plasma osmolarity, thirst, incr renal h2o reabsorption, incr blood V/P
How do the kidneys react to excess salt ingestion?
Incr plasma osmolarity, vasopressin release, incr renal h20 reabsorption, kidneys conserve water
What are the body’s rapid and slow responses to thirst and incr water intake/reabsortion from excess salt ingestion?
Rapid: incr BP from h20 intake causes cardio reflex to decr BP
Slow: incr BV from h20 intake causes kidneys to excrete salt and water
What hormone synthesized in the renal cortex stimulates sodium reabsorption?
Aldosterone
Where does aldosterone act to incr sodium reabsorption? What cells?
Renal distal tubule and collecting duct on principle cells
How does aldosterone incr sodium reabsorption in principle cells?
Hormone incr transcription/translation/formation of basolateral Na/K ATPases which incr Na reabsorption and K excretion
What 3 conditions stimulate aldosterone production (not AT2)?
Low blood V/P, high circulating K, decr plasma osmolarity
How and why does high K stimulate aldosterone release?
How: acts directly on adrenal cortex
Why: aldosterone incr K excretion
What suppresses aldosterone release?
High plasma osmolarity
What system reacts to low BP/V to incr sodium reabsorption?
Renin-angiotensin-aldosterone system (RAAS)
How does the RAAS system incr sodium reabsorption? (6)
Low BP/V stimulates renin release from juxtaglomerular cells in kidney, renin converts angiotensinogen to AT1, angiotensin-converting enzyme converts AT1 to AT2, AT2 stimulates adrenal cortex to produce aldosterone, sodium reabsorbed, BP/V incr
What 3 structures does AT2 act on for sodium/fluid balance?
Brain, vasculature, proximal tubule
How does AT2 in the brain incr BP/V? (3)
Stimulates vasopressin release from hypothalamus (incr renal h2o reabsorption), stimulates thirst (water intake), incr sympathetic outflow (incr CO, vasoconstriction, RAAS)
How does AT2 in vasculature incr BV/P?
Vasoconstriction (ST incr)
How does AT2 incr BV/P in proximal tubule?
Stimulates Na/H Exchanger (NHE) to reabsorb salt and water
What do natriuretic peptides do? (3)
natriuresis (incr sodium excretion), dieresis (incr water excretion) and vasodilation (opposite to aldosterone)
What natriuretic peptides are release from atria vs ventricles?
Atria: atrial natriuretic peptides (ANP, more important)
Ventricles: brain natriuretic peptide (BNP) - originally observed in brain
When is ANP released?
High blood V in response to cardiac stretch
What does ANP cause? (4)
Dilates afferent arterioles, incr GFR, inhibits Na reabsorption in collecting duct, inhibits release of Na/h20 reabsorbing mediators (renin, aldosterone, vasopressin)
Why must K levels be tightly regulated in body? (2)
Protects resting Vm (particularly important for excitable cells in heart, neurons, skeletal muscle) and normal cellular function
What is hypokalemia vs hyperkalemia?
Hypokalemia: low ECF [K]
Hyperkalemia: high ECF [K[
What does hypokalemia cause? (4)
Low ECF [K] causes K to leave cells, Vm more negative (decr excitability), muscle weakness, resp/cardiac dysfunction
What does hyperkalemia cause?
Incr ECF [K] brings K into cells, depolarization, incr excitability followed by depression bcse impaired repolarization (K can’t leave), cardiac arrhythmias
What can cause fluctuation in K levels?
Renal or GI function
What can cause excessive K excretion in urine?
Diuretic drugs (incr h20 loss)
What hormone regulates K balance? How?
Aldosterone; high K stimulates aldosterone secretion, distal tubule incr Na/K ATPases, incr K excretion
What secretes aldosterone?
Adrenal cortex
What causes blood V and osmolarity to both incr?
If salt > fluid intake (still has h2o intake)
What does incr in blood V and osmolarity cause? (2)
Incr ECF V and hypertonic urine
What causes incr blood V but constant osmolarity?
Salt=water ingestion
What does incr blood V and constant osmolarity cause?
Isotonic urine
What causes incr blood V and decr osmolarity?
Pure water ingested
What does incr blood V and decr osmolarity cause? (2)
Dilutes ECF (salt cravings) and large V of hypotonic urine
What causes constant blood V and incr osmolarity?
Solute consumed wo/ water
What does constant blood V and incr osmolarity cause? (2)
Triggers thirst and small V of conc urine
What causes constant blood V and decr osmolarity?
Dehydration and pure water ingested
What does constant blood V and decr osmolarity cause?
Dilute ECF
What is the purpose of sport drinks (ie. Gatorade)?
Prevent diluting ECF and decr plasma osmolarity from pure water ingestion when dehydrated (drink water + electrolyte to maintain balance)
What causes decr blood V and incr plasma osmolarity?
Diarrhea, excessive sweating, etc. (Water > solute loss)
What causes decr blood V and constant osmolarity?
Blood loss (hemorrhage)
How is decr blood V but constant osmolarity treated? (2)
Blood transfusion or isotonic saline infusion (i.v.)
T/f: decr in blood V and osmolarity is rare
True
What 4 mechanisms restore homeostasis during dehydration?
Cardiovascular, RAAS, renal, hypothalamic
What occurs to BV, P and osmolarity during dehydration?
BV/P decr and osmolarity incr
How do cardiovascular mechanisms restore BP during dehydration? (3)
Decr vasculature stretch activates carotid and aortic baroreceptors, cardiovascular control centres in brain decr para output to incr HR and contractility (incr CO), and incr symp output for vasoconstriction to incr R (net incr in BP)
What does incr sympathetic output from cardiovascular brain centres also coordinate (besides peripheral vasoconstriction)? (3)
Incr HR (CO), stimulates granular cells/justaglomerular cells to produce renin, decr GFR by vasoconstriction of afferent arterioles
How does the RAAS system decr plasma osmolarity during dehydration? (3)
Decr BV/P stimulates granular/juxtaglomerular cells to produce renin which converts angiotensinogen to AT1, ACE converts to AT2 which stimulates adrenal cortex (produces aldosterone but net suppression?)
What does AT2 also stimulate (besides aldosterone release) to restore balance when dehydrated? (3)
Stimulates peripheral vasoconstriction (incr BP), incr vasopressin release from posterior pituitary, and stimulates thirst
How do renal mechanisms conserve blood V when dehydrated? (2)
Decr BV/P decr GFR which conserves blood V, decr flow at macula densa stimulates granular/juxtaglomerular cells to produce renin
How is aldosterone net suppressed when dehydrated if decr in BV/P incr AT2/aldosterone?
Incr plasma osmolarity inhibits adrenal cortex production of aldosterone > AT2 stimulation (overall decr Na reabsorption in distal nephron)
How do hypothalamic mechanisms decr plasma osmolarity and incr BV when dehydrated? (2)
Hypothalamic osmoreceptors, atrial V receptors, and carotid and aortic baroreceptors stimulate hypothalamus to release vasopressin from posterior pituitary (incr h2o reabsorption from distal nephron) and stimulate thirst (net incr h20 reabsorption/intake to decr osmolarity and incr BV)
What are 2 sources and 2 forms of H+?
Food < internal metabolism; organic acids (fa, aa, lactic acid) < CO2
T/f: diet and metabolism add significant base to body
False
What rxn converts CO2 to H+?
CO2 + H20 -> H2CO3 (carbonic acid) -> HCO3- (bicarbonate) + H+
What are 3 key processes in pH homeostasis?
Buffer systems, ventilation, renal regulation of H+ and HCO3- ions
What are the 1st, 2nd and final line of defence in pH homeostasis?
1st: buffers
2nd: ventilation
3rd: renal regulation of ions
What process is always present and rapidly prevents pH fluctuations?
Buffer systems
What process rapidly corrects most pH disturbances?
Ventilation
What slower but effective process corrects pH under most circumstances?
Renal regulation of H+ and HCO3- ions
What is a buffer?
A molecule that is able to modulate pH in response to disturbance (not prevention)
How do buffers mostly work in body?
Combine (mostly-incr pH during acidosis) or release H+
Where are buffers located (2) and in what forms?
Cells: proteins, phosphate ions, Hb
Plasma: HCO3- from CO2 or metabolism
How does incr in CO2 cause acidosis?
Incr CO2 causes incr conversion to H+ and HCO3- (doesn’t bind to H+ so net decr in pH)
How does acidosis induce resp compensation? (7, 2 pathways)
Incr plasma [H+] stimulates carotid and aortic chemoreceptors, sensory neurons stimulate resp control centres in medulla, incr APs in somatic motor neurons, incr contraction of ventilation muscles, incr rate/depth of breathing to decr CO2 (decr H). Also incr plasma [CO2] (can cross BBB vs H+) stimulates central chemoreceptors in medulla and interneurons to stimulate resp control centres in same process
How does hypo vs hyperventilation cause acid/alkalosis?
Hypo: decr ventilation, incr CO2, incr conversion to H+ (acidosis, decr pH)
Hyper: incr ventilation, decr CO2, decr conversion to H+ (alkalosis, incr pH)
What are 2 mechanisms of renal acid/base compensation?
Direct: excretion/reabsorption of H+
indirect: excretion/reabsorption of HCO3-
What is the renal process that compensates for acidosis? (4)
Kidneys secrete/excrete H+ into tubule lumen, ammonia (in cell) and HPO4 (in filtrate) act as buffers (NH4 and H2PO4), buffers incr H secretion/excretion (by decr H+ conc in lumen), incr HCO3-/H production as [H+] decr (bicarbonate reabsorbed into blood)
What occurs to renal processes in alkalosis?
(Are reversed) HCO3- excreted and H+ reabsorbed to decr pH
How long do renal responses to acid/alkalosis take to be apparent?
24-48 hours
What are 5 renal transporters in acid-base balance?
Apical Na/H exchanger (NHE), basolateral Na/HCO3 symporter, H ATPase (proton pump), H/K ATPase, Na/NH4 antiporter
What does the apical Na/H exchanger (NHE) do?
Brings Na into cell, moves H into lumen against conc grad
What does the basolateral Na/HCO3 symporter do?
Moves Na and HCO3 out of cell into interstitium
What does the H+ ATPase (proton pump) do?
Moves H+ into lumen of distal nephron (tubule/collecting duct) against conc grad
What does the H/K ATPase do?
Moves H+ into lumen and K into cell (K imbalances in acid/base disturbances)
What does the Na/NH4 antiporter do?
Moves NH4 into lumen and Na into cell
how are H+ ions secreted into filtrate from proximal tubule cell?
NHE transporter (H out, Na in)
what do H+ ions combine w/ in filtrate at proximal tubule? what do they form?
HCO3- to form CO2 (and H2O)
how does CO2 (and H2O) in filtrate at proximal tubule move into tubule cell?
diffusion
what occurs to CO2 and H2O in proximal tubule cell?
combine to form H+ and HCO3- (H+ is secreted again)
how is HCO3- reabsorbed from proximal tubule cell?
basolateral Na/HCO3 symporter (both moves into interstitum)
what is glutamine metabolized into in proximal tubule cell?
NH4 (ammonium ion) and HCO3- (from a-ketoglutarate)
what are excreted from proximal tubule filtrate? (2)
NH4+ and H+
which cell functions during acidosis vs alkalosis in distal nephron?
acidosis: type a intercalated cells
alkalosis: type b intercalated cells
what ions are reabsorbed vs secreted in type a intercalated cells (acidosis)?
reabsorbed: HCO3- and K+
excreted: H+
what ions are reabsorbed vs secreted in type b intercalated cells (alkalosis)?
reabsorbed: H+
secreted: HCO3- and K+
what is the process of HCO3- and K+ reabsorption and H+ excretion in type a intercalated cells (acidosis)? (5)
H from interstitum combines w/ HCO3- to form CO2 and H2O, diffuse into cell, recombine w/ carbonic anhydrase to form H and HCO3-, H transported into lumen w/ H/K ATPase, HCO3- moved out of cell w/ HCO3-/Cl- anti porter
what is the process of HCO3- and K+ excretion and H+ reabsorption in type b intercalated cells (alkalosis)? (3)
H2O and CO2 in cell combine to form HCO3- and H w/ carbonic anhydrase, HCO3- moved into lumen w/ HCO3-/Cl- antiporter, H moved into interstitium w/ H/K ATPase
what transporters do type a and b intercalated cells use in distal nephron? (3)
H/K ATPase and HCO3-/Cl- antiporter (also proton pump)
what side of the cell are H/K ATPases, HCO3-/Cl- antiporters, and proton pumps on in type a intercalated cells use in distal nephron?
H/K ATPase and proton pump on apical side (bring H into lumen), HCO3-/Cl- antiporter on basolateral side (HCO3 into interstitum)
what side of the cell are H/K ATPases, HCO3-/Cl- antiporters, and proton pumps on in type b intercalated cells use in distal nephron?
H/K ATPase and proton pump on basolateral side (bring H into interstitum), HCO3-/Cl- antiporter on apical side (HCO3 into lumen)
what enzyme is in high conc in type a and b intercalated cells use in distal nephron?
carbonic anhydrase (rxns of CO2, H2O, HCO3-, H+)
what are 2 causes for acid/base imbalances and their causes?
metabolic (not from CO2), respiratory (hypo/hyperventilation-CO2)
t/f: if plasma pH is altered, buffer system has already failed
true
t/f: if acid/base imbalance is caused by respiratory changes, kidneys cannot compensate
false, if acid/base imbalance is caused by respiratory changes, ONLY kidneys can compensate
what are 5 causes of respiratory acidosis?
drug effects (hypoventilation), incr airway R, decr alveolar gas exchange, muscular dystrophy, chronic obstructive pulmonary disease (COPD, most common)
what is the renal compensation for respiratory acidosis?
H+ excreted, HCO3- reabsorbed
what are 5 causes of metabolic acidosis?
incr dietary/metabolic H+ (>excretion), lactic acidosis (anaerobic resp), ketoacidosis (fa, aa met), ethylene glycol ingestion, decr HCO3-
what is the respiratory and renal compensation for metabolic acidosis?
resp: hypervetialtion (remove CO2)
renal: incr H+ excretion and HCO3- reabsorption
what is a cause for respiratory alkalosis?
hyperventilation (mechanical ventilator anxiety, decr CO2)
what is the renal compensation for respiratory alkalosis?
HCO3- excretion to decr buffer load and incr H+ (decr pH)
what are 2 causes for metabolic alkalosis?
excessive vomiting (loss of stomach acid), excessive antacid use (decr H+/incr pH)
what is the respiratory and renal compensation for metabolic alkalosis?
resp: hypoventilation (incr CO2)
renal: HCO3- excretion and H+ reabsorption
