A&P Lecture 7 - Renal Physiology

Functional unit of the kidney

Nephron, with 4 main sections (glomerular/Bowman's capsule, proximal tubule, loop of Henle, distal tubule, collecting duct)

Two types of nephrons

Cortical (mostly in renal cortex) and juxtamedullary (extend into medulla, ~20%, produce most concentrated urine)

Glomerular (Bowman's) capsule function

Collection area for filtered plasma

Proximal tubule (PCT) function

Reabsorbs 60-80% of filtrate

Loop of Henle function

Produces osmotic gradient allowing concentration of urine

Distal tubule (DCT) function

Creates small modifications to urine composition

Collecting duct function

Regulates urine's final composition

Nephron regeneration

Cannot be regenerated if they die

Filtration

Movement of fluid from blood into nephron lumen, occurs at renal corpuscle (glomerulus + capsule); RBCs and large proteins NOT filtered

Reabsorption

Movement of substances from tubule lumen back into blood (e.g., glucose 100% reabsorbed)

Secretion

Movement of substances from blood into tubule lumen (active process, against gradients)

Excretion

Substances not reabsorbed that exit as urine (e.g., creatinine 100% excreted, water variably reabsorbed/excreted)

Key solute equation

F (filtered) − R (reabsorbed) + S (secreted) = E (excreted)

Renal blood flow (RBF)

Total blood flow through kidneys; calculated at renal artery; measure of kidney perfusion

Renal plasma flow (RPF)

~20% of plasma entering kidney that filters into nephrons; calculated at afferent arteriole; measure of glomerular filtration rate

Filtration fraction

Amount filtered / amount entering afferent arteriole; normal example = 0.2

Three pressures controlling glomerular filtration

Capillary hydrostatic pressure (PH, favors filtration, ~55mmHg), capillary oncotic pressure (π, opposes filtration, ~30mmHg), capsule fluid pressure (Pfluid, opposes filtration, ~15mmHg)

Net filtration pressure formula

PH − π − Pfluid = net filtration pressure (normal = 55−30−15 = 10mmHg)

GFR definition

Volume of fluid entering Bowman's capsule per unit time; normal adult average = 125mL/min

GFR clinical use

Chief measure of kidney function; clinically estimated using blood creatinine levels

Easiest way to increase GFR

Increase renal blood flow by dilating afferent arteriole

Afferent arteriole constriction effects

↓RBF, ↓hydrostatic pressure, ↓GFR

Afferent arteriole dilation effects

↑RBF, ↑hydrostatic pressure, ↑GFR

Efferent arteriole constriction effects

↓RBF, ↑hydrostatic pressure, ↑GFR

Efferent arteriole dilation effects

↑RBF, ↓hydrostatic pressure, ↓GFR

Drugs affecting efferent arteriole

ACE inhibitors and ARBs dilate efferent arterioles (↓GFR)

Drugs affecting afferent arteriole

NSAIDs cause afferent constriction → ↓RBF and ↓GFR

Sodium's role in reabsorption

Primary driving force of most renal reabsorption; drives reabsorption of glucose, amino acids, and water

Na+ reabsorption mechanism

Na+ enters tubule cell via apical membrane proteins (down concentration gradient), then pumped out basolaterally by Na+-K+-ATPase into interstitial fluid; K+ leak channels prevent K+ buildup

Sodium-glucose cotransport (SGLT)

Na+ moving down its gradient drives glucose into cell against its gradient (secondary active transport); glucose then exits via GLUT on basolateral side

Glucose/amino acid reabsorption site

Completely reabsorbed in proximal convoluted tubule

Hydration shells and diuretics

Na+ and H2O travel together (water attracted to charged ions); diuretics ↓Na+ reabsorption, so H2O follows into urine — used to treat edema and hypertension

Site of water absorption

Throughout nephron, especially descending loop of Henle (passive) and collecting duct (variable, ADH-regulated)

Descending loop of Henle permeability

Permeable to H2O (water exits, ions stay) → osmolarity increases

Ascending loop of Henle permeability

Permeable to ions (ions exit, water stays) → osmolarity decreases

Osmolarity gradient pattern

Highest at tip of medulla (~1200 mOsM), decreases toward cortex (~300 mOsM at corticomedullary junction after ascending limb)

Vasopressin (ADH) mechanism

Controls aquaporin insertion in collecting duct apical membrane; +ADH = more pores, ↑permeability, H2O reabsorbed (concentrated urine); −ADH = fewer pores, dilute urine

Countercurrent mechanism components

Loop of Henle and vasa recta, with fluids flowing in opposite directions for efficient exchange

Countercurrent mechanism outcome

Maintains medullary concentration gradient; allows regulation of urine concentration and water/waste removal

Hormonal factors affecting ECF osmolarity

Vasopressin (ADH) and aldosterone

Behavioral factor affecting ECF osmolarity

Thirst (increases water intake, dilutes osmolarity)

Aldosterone source and action

Produced by adrenal cortex; acts on principal cells of distal tubule/collecting duct; ↑Na+ reabsorption, ↑K+ and H+ secretion

Aldosterone and acid-base

Increased H+ secretion causes alkalosis

Aldosterone release triggers

Decreased blood pressure (via RAS) and hyperkalemia (direct stimulation)

RAAS necessity

Maintains blood pressure when BP drops (↓RBF, ↓GFR sensed by kidney)

RAAS pathway steps

Renin (released from afferent arteriole) converts angiotensinogen → angiotensin I; ACE (in lungs) converts angiotensin I → angiotensin II; angiotensin II causes vasoconstriction (↑BP) and stimulates aldosterone release

RAAS downstream effects

Na+ reabsorption (↑osmolarity), ↓ANP release, ↑thirst — all raise blood volume/pressure/GFR

ANP/BNP source and trigger

Atrial natriuretic peptide/brain natriuretic peptide; released due to increased atrial stretch from ↑blood volume

ANP/BNP action

RAS antagonists; suppress renin, aldosterone, vasopressin; enhance Na+ and H2O excretion; dilate afferent arterioles and constrict efferent arterioles → ↑GFR

ANP/BNP clinical use

Treat volume excess (edema) and hypertension

Body water percentage

~60% of body weight is water

ICF vs ECF proportions

ICF ~65% of total body water (within cells); ECF ~35% (includes plasma ~8% of total body water)

Plasma vs serum

Plasma = fluid portion of blood (no RBCs/WBCs); serum = plasma minus clotting factors and fibrinogen

Filtrate definition

Fluid taken from blood into the nephron (similar composition to plasma minus large proteins/cells)

Urinalysis color findings

Dark yellow = concentrated; pale straw = dilute; red = blood; black = hemoglobin metabolites

Urinalysis clarity findings

Cells/particles/stones present; frothiness indicates proteins

Urinalysis odor findings

Ammonia smell = high pH; sweet smell = diabetes mellitus

Kidney functions (6 major)

(1) ECF volume/BP regulation, (2) osmolarity regulation via Na+, (3) ion balance, (4) pH homeostasis, (5) waste excretion (urea, uric acid, creatinine), (6) hormone production (erythropoietin, renin, active vitamin D)

Waste product origins

CO2 (fat/carb/protein metabolism), urea (nitrogen from proteins), uric acid (nucleic acids/ATP/GTP), creatinine (creatine phosphate from muscle), bilirubin/urobilinogen (hemoglobin breakdown)

Routes of excretion

Lungs (CO2), kidneys (urea, creatinine, uric acid, H+, NH4+, salts, H2O), feces (bile salts, cholesterol, salts), skin (sweat

Saturation/transport maximum (Tm)

Below saturation, transport rate proportional to [substrate]; at Tm, all carriers saturated and excess substrate (e.g., glucose) is excreted unreabsorbed

Renal threshold

Plasma concentration at which saturation/Tm occurs

Glomerular filtration barriers

Fenestrated endothelial cells, fused basement membrane (basal lamina), podocytes, and negatively charged heparan sulfate (mesangium is NOT a barrier)

Vascular pole vs urinary pole

Vascular pole = where blood enters/exits glomerulus (afferent/efferent arterioles); urinary pole = where filtrate exits into proximal tubule

Dehydration response

↓blood volume/BP, ↑osmolarity → activates RAAS, ↓aldosterone (due to hyperosmolarity), ↑thirst, ↑vasopressin → restores volume/BP

Salt ingestion response

↑osmolarity (no volume change) → ↓aldosterone, ↑thirst, ↑vasopressin → ↑water intake/reabsorption → restores osmolarity; resulting ↑ECF volume corrected by kidney/CV adjustments

Volume/osmolarity changes - water excess (e.g., drinking large water amount)

↑volume, ↓osmolarity

Volume/osmolarity changes - hypertonic saline ingestion

↑volume, ↑osmolarity

Volume/osmolarity changes - dehydration (sweat loss/diarrhea)

↓volume, ↑osmolarity

Volume/osmolarity changes - hemorrhage

↓volume, no change in osmolarity

Volume/osmolarity changes - isotonic saline ingestion

↑volume, no change in osmolarity

Volume/osmolarity changes - salt ingestion without water

No volume change, ↑osmolarity

Excess aldosterone effect

Alkalosis, hypokalemia, and hypernatremia

Substance most likely to be in filtrate (excluding cells/large proteins)

Angiotensin II (8 amino acids, small enough to filter) — WBCs, RBCs, platelets, albumin, IgG are NOT filtered

Substance least likely in Bowman's space filtrate

Albumin (too large to be filtered)

GFR estimation marker (clinical/routine)

Creatinine (inulin is gold standard but not routine)

Camel kidney adaptation

Many juxtamedullary nephrons for water conservation in desert