L1: Intro to Kidneys

summary:

general fx - acid/base balance

-most important factor of long-term balance

-to keep blood pH normal (~7.35–7.45)

-kidneys produce bicarb (HCO₃^-) buffers to combat acids

what are some acids that are produced by the body?

-lactic acid

-ketoacids

-sulfuric acid from protein breakdown (can only be excreted by kidneys)

-CO₂ from metabolism

acid/base balance:

how do the kidneys maintain pH balance?

-reabsorbing filtered bicarbonate (HCO₃⁻)

-excreting hydrogen ions (H⁺)

-generating new bicarbonate

acid/base balance:

time frame - resp & renal systems

Respiratory: minutes to hours (quick changes to CO₂ while breathing)

Renal: hours to days (chronic changes to base levels (bicarb))

acid/base balance:

kidney

1st step: reabsorption of filtered bicarbonate

1. Tubule cells secrete H⁺ into the lumen via Na⁺/H⁺ exchangers.

2. H⁺ combines with HCO₃⁻ in the filtrate → forms carbonic acid (H₂CO₃).

3. Carbonic anhydrase breaks it down into CO₂ + H₂O.

4. CO₂ diffuses back into the cell → recombines with water → regenerates HCO₃⁻.

5. This “recycled” bicarbonate goes into the blood.

where does most of the bicarbonate reabsorption occur?

(80-90%)

-proximal tubule but it does not cross cell membranes well so has to be broken down

acid/base balance:

kidneys

2nd step - Secretion of H⁺ ions

-actively pump out H⁺ via H⁺-ATPases and H⁺/K⁺ ATPases.

-pH fine-tuning

acid/base balance:

kidneys

3rd step - generation of new bicarbonate

• When acids are excreted, the kidney produces “new” HCO₃⁻ to replace what was lost in buffering.

• Two main urinary buffers help with this:

  1. Phosphate buffer system:
     HPO₄²⁻ + H⁺ → H₂PO₄⁻ (excreted)

  2. Ammonia buffer system:

     • Tubule cells metabolize glutamine → produce NH₃ and HCO₃⁻.

     • NH₃ binds H⁺ to form NH₄⁺ (trapped in urine).

     • HCO₃⁻ enters blood as a fresh buffer.

where does H⁺ ion secretion occur?

-distal tubules

-collecting ducts

general:

how does the kidney regulate RBC production?

-by controlling the hormone, erythropoietin (EPO)

RBC production:

what cells sense O₂ levels in the blood?

-peritubular interstitial fibroblast-like cells (around the proximal tubules)

RBC production:

what are HIFs?

hypoxia inducible factors (HIFs)

-broken down when O₂ abundant

-stabilized when hypoxic → into cell nucleus → trigger EPO gene transcription →

RBC production:

general EPO movt

HIF → nucleus → EPO gene transcription → bone marrow → erythroid progenitor cells divide and mature → shuts off EPO signal (neg. feedback loop)

what are the (3) hormones produced by the kidneys?

-eythropoietin (EPO)

-renin

-calcitriol (1,25-dihydroxyvitamin D₃)

what (3) hormones are activated by the kidneys?

-Angiotensin II

-Prostaglandins

-Kallikrein

summary:

renin

(hormone)

-released in response to low BP, low sodium, or sympa

-kicks of RAAS

what is the active form of vit. D?

-calcitriol (1,25-dihydroxyvitamin D₃)

-1,25-dihydroxyvitamin D₃

-1,25-dihydroxycholecalciferol

summary:

kallikrein

(hormone)

-fine tunes BP & Na⁺

-serine protease enzyme

-produced in connecting tubule & early cortical collecting duct

fx: activate kinins

fx:

kallikrein

-activate kinins from kininogen

-low-MW kininogen → bradykinin

fx:

bradykinin

(vasodilator)

-expands renal blood vessels → increases renal blood flow.

-increases sodium excretion (natriuresis)

-promotes water excretion (diuresis)

what stimulates kallikrein?

-high K

-high Na intake

-adosterone

what system counter-regulates RAAS?

-kallikrein–kinin system

what two systems help regulate BP?

-RAAS

-kallikrein–kinin system

fx:

RAAS

-maintain BP, BV, Na balance (esp during dehydration, bleeding, low salt intake)

-conserves Na and H₂O

-constricts blood vessesl

-restores BP and perfusion

-basically: helps body retain necessities

RAAS cascade

juxtaglomerular (JG) cells release renin → cleaves angitensinogen into angiotensin I → ACE (angiotensin converting enzyme converts to angiotensin II

what triggers the release of renin?

-low BP

-low Na⁺

-sympa activation

fx:

angiotensin II

-vasoconstriction

-stimulates aldosterone release (Na reabsorption)

-stimulates ADH (water reabsorption)

-triggers thirst (hypothalamus)

summary:

creatinine

-waste product generated from muscle metabolism and protein breakdown

-filtered by the kidneys and excreted in urine

summary:

urea

-N-containing substance produced when the body breaks down protein

-waste product filtered by kidneys, excreted in urine

-ammonia converted by liver to urea → kidneys via blood

summary:

uric acid

-formed by purine breakdown

definition:

GFR

-the V of plasma filtered into the renal tubules by the glomeruli per unit time

-how much fluid kidneys turn into filtrate/min

what is the normal GFR of humans?

180 L/day

what factors influence GFR?

-spp

-size

-metabolic rate

eq:

GFR

GFR = K_f × (P_GC​−P_BS​−π_GC​)

K_f = filtration coefficient (surface area × permeability).

P_GC = glomerular capillary hydrostatic pressure (pushes fluid out).

P_BS​ = hydrostatic pressure in Bowman’s space (pushes back).

π_GC= oncotic pressure of plasma proteins (pulls fluid back into capillary).

what hormones affect GFR?

-angiotensin II

-prostaglandins

-ANP

what happens to GFR if blood V falls?

-renal perfusion P falls → GFR can no longer occur

-works based on P gradient

importance:

calcitriol

-normal Ca²⁺ deposition in bone

-Ca²⁺ reabsorption by GIT

gluconeogenesis:

renal cortex

-undergoes gluconeogenesis from AAs and other precursors

-can be 20% of circulating glucose

which sp is most prone to kidney disease?

-domestic animals, mainly fels

fx:

kidney (7)

-excretion of metabolic waste products, foreign chemicals, drugs and hormone metabolites

-regulation of water and electrolyte balances

-regulation of arterial P

-regulation of RBC production

-activation of vit D

-regulation of acid-base balance

-gluconeogenesis