Renal Acid-Base Regulation, Calcium and Phosphate Balance

what is normal blood pH?

7.4

a _____-fold increase in H+ concentration represents 1 unit pH change

10

what are the consequences of a pH disturbance?

1. denatures proteins and affects structure and function 

2. affects CNS and excitable tissues with alkaline environment decreasing excitability, and acidic environment increasing excitability 

acid-base disturbances often result in changes to __________ levels

potassium 

where does H+ input come from?

1. CO2

2. lactic acid 

3. ketoacids 

______ is termed a volatile acid

CO2

what is the largest source of acid input under normal conditions?

H+ from CO2 and H2O

what do the carotid and aortic chemoreceptors sense?

increased H+, decreased pH

what do the central chemoreceptors sense?

increased PCO2

how do the respiratory control centers in the medulla respond to increased PCO2 and decreased pH?

innervate muscles of ventilation to increase rate and depth of breathing

fixed acids

1. ketoacids from fat metabolism 

2. phosphoric and sulfuric acid from protein metabolism 

3. lactic acid from carbohydrate metabolism 

3 levels of response to a change in acid-base status

1. buffers

2. ventilation 

3. renal adjustment 

intracellular buffers

1. proteins

2. phosphate ions 

3. hemoglobin 

extracellular buffer

bicarbonate ions

urine buffers

1. phosphates

2. ammonia

what is the largest source of buffer within the extracellular fluids?

bicarbonate 

henderson-hasselbach equation to show relationship between pH, HCO3-, and PCO2

pH = 6.1 + log( [HCO3-] / 0.3*PCO2 ) 

2 main ways that kidneys handle acid-base changes

1. reabsorption of HCO3-

2. excretion of H+

the kidneys will ______ and ________ more than 99.9% of HCO3-

filter, reabsorb 

the kidney excretes a ________ amount of H+ that is produced from protein and phospholipid catabolism 

fixed 

the excretion of H+ results in the synthesis and reabsorption of a new _______

HCO3-

H+ is excreted by the kidneys in what form?

titratable acid or NH4+

HCO3- reabsorption occurs mainly in the __________ tubule

proximal

carbonic anhydrase 

catalyzes conversion of CO2 and H2O into H+ and HCO3-

titratable acids are primarily excreted in the _____________ cells of the _________ and _________

alpha-intercalated, distal tubule, collecting duct

for each H+ excreted as TA…

one new HCO3- is synthesized and reabsorbed

the _____________ secretes NH4+

proximal tubule

the collecting duct secretes ______ and ______ into the lumen, which combine to form _______ and are excreted 

NH3, H+, NH4+

renal acid excretion RAE formula

RAE = V ( [TA] + [NH4+] - [HCO3] )

if RAE > 0…

net acid excretion

if RAE < 0…

net base excretion

it is rare to see a ________ RAE, because bicarbonate is typically absent from the urine 

negative 

respiratory acidosis: PCO2, H+, pH, and HCO3-

1. increased PCO2

2. increased H+

3. decreased pH

4. increased HCO3-

metabolic acidosis: PCO2, H+, pH, and HCO3-

1. PCO2 normal or decreased

2. H+ increased 

3. pH decreased 

4. HCO3- decreased 

respiratory alkalosis: PCO2, H+, pH, and HCO3-

1. PCO2 decreased 

2. H+ decreased 

3. pH increased 

4. HCO3- decreased 

metabolic alkalosis: PCO2, H+, pH, and HCO3-

1. PCO2 normal or increased

2. H+ decreased

3. pH increased 

4. HCO3- increased 

cause of respiratory acidosis

hypoventilation

causes of metabolic acidosis

1. diabetes 

2. inability to excrete fixed acids (loss of functional nephrons)

type A intercalated cells

1. in collecting duct 

2. function in acidosis 

3. H+ excreted 

4. HCO3- and K+ are reabsorbed 

type B intercalated cells 

1. in collecting duct

2. function in alkalosis

3. HCO3- and K+ are excreted

4. H+ is reabsorbed

cause of respiratory alkalosis

hyperventilation

causes of metabolic alkalosis

1. ingesting bicarbonate 

2. vomiting 

calcium phosphate crystals (bone formation)

they precipitate and attach to cartilaginous support to form bone

bone is a __________ tissue

dynamic

bone is supplied with ________ and _________ via a blood supply that penetrates into spaces of the ______________ matrix

oxygen, nutrients, collagen-calcium 

outer layer of bone

compact bone that provides strength

inner layer of bone

trabecular and forms a calcified lattice

a central cavity is present in some bone that houses ___________

bone marrow

epiphysis

the end of a long bone

epiphyseal plate 

1. located at each end of the bone shaft

2. site of bone growth

diaphysis

the shaft of a long bone

hydroxyapatite 

calcium phosphate crystals 

osteoblasts

create bone by making calcium phosphate crystals to replace cartilage

osteoid

matrix of collagen and proteins secreted by osteoblasts to which hydroxyapatite binds

chondrocytes

produce cartilaginous layers in the epiphyseal plate

old chondrocytes ___________, leaving holes for osteoblasts to lay down bone matrix within 

disintegrate 

bone lengthening is regulated by…

1. growth hormone

2. insulin growth factor

3. sex hormones

in adulthood, there is a continuous cycle of activity favoring ___________ or ____________ (bones)

osteoblasts, osteoclasts

osteoclasts

responsible for bone resorption

mechanical loading to the bone

induces stress that stimulates bone development and osteocytes

how do osteoclasts promote bone resorption?

they secrete acid and enzymes that dissolve calcium phosphate

in late-adulthood, bone resorption begins to exceed formation, rendering individuals more susceptible to fractures and ___________

osteoporosis

largest reservoir for calcium in the body

bone (extracellular matrix)

intake of calcium

1. ingested in diet

2. 30% absorbed in across walls of small intestine 

3. regulated by vitamin D 

output of calcium

1. freely filtered at nephron

2. 60-70% reabsorbed by proximal tubule

3. regulated reabsorption in distal nephron by hormones

fates of phosphate in the plasma after absorption in the GI tract

1. transport into cells 

2. deposition into bone or soft tissue

3. renal elimination 

largest phosphate store in the body

bone or soft tissue

plasma levels of phosphate represent ______% of total body phosphate availability 

<1

renal phosphate handling

1. freely filtered

2. 75-85% is reabsorbed mainly in the proximal tubule

parathyroid hormone PTH is released when? 

hypocalcemia (low plasma calcium)

what inhibits PTH release?

calcium binding to the parathyroid gland

PTH action on the bone

1. stimulates osteoclast differentiation 

2. increased bone breakdown 

3. calcium released into blood 

PTH action in the kidney

1. increases reabsorption of calcium in ascending limb and distal tubule

2. increases phosphate excretion by suppressing phosphate transport mechanisms of proximal tubule 

calcitriol

1. promotes bone resorption 

2. increases GI absorption of calcium and phosphate

3. increases renal phosphate reabsorption 

calcitonin

1. released by thyroid in response to hypercalcemia

2. reduces GI absorption of calcium and phosphate 

3. reduces bone resorption 

4. reduces calcium reabsorption and phosphate excretion 

calcitriol inhibits _______ release

PTH

response to hypophosphatemia

1. calcitriol is released 

2. PTH is inhibited 

3. GI has increased calcium and phosphate absorption 

4. increased bone resorption 

5. reduced renal calcium reabsorption and increased phosphate retention 

increased serum phosphate is associated with…

cardiovascular morbidity and mortality

hyperphosphatemia is associated with a decline in ______

GFR