Kidney Anatomy and Physiology

where are the kidney’s located?

either side of the spine, just below the ribcage; sit behind the abdominal cavity in the retriperitoneal space; right kidney tends to be a little bit lower due to the presence of the kidney; along the posterior abdominal wall

what are the dimensions of the kidney?

10 × 7 × 3 cm

what is the blood supply of the kidneys?

renal arteries and renal veins

structures related to the kidneys

ureters, bladder, urethra, adrenal glands

nephron

kidney’s functional unit, approximately 1,2 million nephrons per kidney

renal corpuscle

glomerulus (enclosed by Bowman’s capsule), blood vessels

Bowman’s space

site of filtration; there is a parietal and a visceral layer

proximal convoluted tubule

REABSORPTION: reabsorbs glucose, sodium, chloride, amino acids and peptides; secretion from blood to lumen and reabsorption from lumen to blood

proximal tubule

SECRETION: bile salts, urate, drugs

loop of Henle

REABSORPTION: reabsorbs water and electrolytes

distal convoluted tubule

selective reabsorption

collecting duct

selective reabsorption and excretion, regulated by ADH

filtration apparatus structure

there are three layers to it: a fenestrated endothelium, the basement membrane, and the visceral layer of Bowman’s capsule, which consists of podocytes and slit diaphragm (SD) proteins

filtration apparatus function

the apparatus is not permeable to large molecules such as albumin, but it is permeable to small molecules, such as water, glucose, electrolytes and vitamins

damage to filtration apparatus

through infection, trauma and diabetes, for example; damage leads to proteinuria

main functions of the kidney

1. filter the blood and excrete water-soluble waste in the urine/regulate total volume of water in the body; concentrate urine appropriately according to osmotic status of the body (ADH regulates water absorption)

2. regulate hemodynamic/blood pressure via the renin-angiotensin-aldosterone system (RAAS)

3. maintain bone metabolism via selective excretion/reabsorption of Ca and phosphate, kidney activates vitamin D and converts it into its active form

4. aid in RBC formation via secretion of erythropoietin (EPO)

5. regulate acid-base status via excretion of H+ and reabsorption of bicarbonate

where does the force for ultrafiltration into Bowman’s space come from?

the hydrostatic pressure gradient

GFR

glomerular filtration rate: how much is filtered by the kidneys

normal GFR

varies with age and sex, but around 120 mL/minute/1.73 m²; so in healthy adults 170 L

filtration

plasma is filtered from the blood

reabsorption

useful materials, such as water, ions, glucose are reabsorbed

glucose spill

normally, glucose in the blood is filtered by the glomerulus, but there is a maximum capacity for reabsorption, so if glucose in the blood exceeds the limit, glucose will appear in the urine as not all of it can be absorbed

secretion

elimination of metabolic waste products

excretion

remainder is excreted as urine

ADH

ADH is produced by the hypothalamus. the osmoreceptor cells in the hypothalamus monitor solute concentration; the posterior pituitary releases ADH when the blood solute concentration (osmolarity) increases or when blood pressure or volume decreases. the release of ADH can also be triggered by pain and drugs, and its release is inhibited by alcohol and diuretics. the release of ADH makes the kidneys reabsorb more water to preserve blood volume, and hence less urine is produced.

ADH and high concentrations

ADH is also called vasopressin because it makes blood vessels constrict to increase bp (especially when bp is very low due to blood loss for example)

sweating on a hot day and ADH

leads to water loss, which makes the blood more concentrated with solutes; osmoreceptor cells in the hypothalamus are triggered by the high concentration, and the hypothalamus alerts the posterior pituitary to release ADH; ducts more permeable to water, so water can move from the tubules to the blood

RAAS

renin-angiotensin-aldosterone system: angiotensinogen, which is a pre-enzyme, is released by the liver; it gets converted into angiotensin I by renin, which is an enzyme produced by the kidneys: the release of renin is triggered by low fluid volume moving through the nephron; angiotensin I gets converted into angiotensin II via ACE (angeotensin converting enzyme) which is released from the lungs; angiotensin II acts on the adrenal gland and causes it to release aldosterone (steroid hormone), which acts on the CD of the nephron and causes the nephron to retain water, which causes bp to go up

what is the direct way in which angiotensin II acts?

it stimulates vasoconstriction

juxtaglomerular apparatus

regulates flow and filtration of each nephron; macula densa senses the salt NaCl in tubular fluid (distal tubule), a decrease of salt triggers constriction of the efferent arteriole which leads to an increase in GFR, and it triggers renin release so activates RAAS

maintenance of bone metabolism

vitamin D needs to be hydroxylated in the liver and kidney to be converted into its metabolically active form hydroxycholecalciferol; this metabolically active form (calcitriol) increases absorption of calcium and phosphate from food, which in turn ensures that enough calcium and phosphate are available for proper bone mineralization

chronic kidney failure and bones

the activity of hydroxylase is reduced, which means that the vitamin D activation is impaired, leading to a reduction in the absorption of calcium and phosphate which in turn results in impaired bone mineralization, which is also called secondary hyperparathyroidism

EPO

erythropoietin: glycoprotein produced by the peritubular cells of the kidney: PO2 (partial oxygen pressure) regulates its production; when PO2 is down, EPO production is up (kidney is getting the signal that the body is not getting enough oxygen)wha

what does EPO stimulate

EPO stimulates the division and differentiation of erythroid progenitor cells (immature blood cells in the bone marrow that develop into RBCs) by binding with EPO receptors on the surface of hematopoietic stem cells, thus promoting cell proliferation and preventing apoptosis

CKD and EPO

decreased erythroprotein production, fewer RBCs made; normochromic normocytic aneamia, (RBCs normal in size and color, just too few)

summarize EPO formation and stimuli

stimulus: hypoxia due to decreased RBC count, decreased hemoglobin, decreased oxygen availability; kidney (and liver) release erythropoietin, EPO stimulates red bone marrow, enhanced EPO increases RBC count, O2 carrying capacity of blood improves

angiotensin II trigger and pathway, site of action and net effect

synthesized in response to hypotension, afferent and efferent arteriole, affarent and mainly efferent arteriolar constriction leading to a rise in GFR

compensatory sodium absorption occurs in the proximal and distal tubule to maintain fluid balance (via water osmosis following sodium)

ANP trigger and pathway, site of action and net effect

released in response to increased atrial pressure, afferent and efferent ateriole and DCT, afferent arteriolar dilation and efferent arteriolar constriction leading to overall GFR rise and increase in Na filtration

at the DCT also inhibits sodium uptake to ensure volume loss

vitamin d3 trigger and pathway, site of action and net effect

hypocalcemia, at DCT, increased calcium uptake

PTH trigger and pathway, site of action and net effect

hypocalcemia and hyperphosphatemia and/or low vitD levels, ascending limb of loop of Henle and DCT, increased Ca uptake

aldosterone trigger and pathway, site of action and net effect

hypovolemia and hypotension (via ang II) and/or hyperkalemia, CD, increased Na uptake and K excretion into the urine, causes net fluid retention

ADH trigger and pathway, site of action and net effect

hypovolemia and hypotension, via Ang II, increased plasma osmolarity, CD, increases free water uptake from the CD

is GFR difficult to measure

yes!

eGFR

estimated GFR, best index for kidney function, serum creatinine, age, sex (eFRG)

serum creatinine

serum is the liquid part of blood (after clotting, without cells/clotting proteins)

creatinine is a waste product formed via the breakdown of creatinine phosphate in muscle how

how is serum creatinine used as a marker for kidney function?

the kidneys filter creatinine out of the blood via the glomeruli; if kidney function and GFR drops, creatinine levels in the blood will rise

serum creatinine is

freely filtered (almost all of it passes into Bowman’s capsule), not reabsorbed (like glucose, sodium and water), and slightly excreted (slightly overestimated kidney function (GFR))

BUN

blood urea nitrogen, kidney function marker (alongside serum creatinine); it is freely filtered (like creatinine), but partially reabsorbed in the tubules, especially when the water tries to preserve water, so it’s less accurate

albumin

protein found in the blood plasma, too large to pass the glomerular filtration barrier

albuminuria

indicates damage of the glomerular filtration barrier (a compromised GFB allows albumin to leak through the barrier when it would normally not be able to)

what diseases are associated with albuminuria?

hypertension, glomerulonephritis, nephropathy