Renal System

Kidney functions

water regulation, balance of inorganic ions, removal of metabolic waste products, and endocrine functions.

Nephron

Functional unit of the kidney. 2.5 million in the kidneys

Glomerular Filtrate

Fluid that drains into the Bowman's capsule and eventually becomes urine.

adaptations of the glomerulus and Bowman’s capsule

Pores in the glomerular endothelium, negatively charged podocytes and the basement membrane

Macula Densa

Specialised cells in the DCT that sense GFR

Juxtaglomerular Apparatus

Includes juxtaglomerular cells which secrete renin. Indirectly modulates sodium ion balance and systemic blood pressure.

What is glomerular flow rate (GFR) controlled by?

sympathetic vasoconstrictor nerves, diameters of afferent and efferent arterioles, ADH and the renin-angiotensin-aldosterone system

Renin-Angiotensin-Aldosterone System (RAAS)

Controls blood pressure and is released in response to reduced blood flow.

autoregulation of blood pressure

maintains blood supply and prevents high pressure surges from damaging the kidneys

kidneys as long-term blood pressure control

control blood volume. Reduced renal pressure → intrarenal distribution of pressure and increased absorption of salt and water

What stimulates renin production?

decreased blood pressure, decreased macula densa [NaCl] or decreased renal perfusion pressure

Aldosterone functions

• Na+ reabsorption

• K+ excretion by renal tubule

• indirect negative feedback on RAAS by increasing ECV and decreasing plasma [K+]

• conserves [Na+] and water

• prevents large [K+] fluctuations

Angiotensin II

Causes renal vasoconstriction, stimulates aldosterone production from the adrenal cortex → sodium absorption and increased IV blood volume.

How does angiotensin II enhance tubuloglomerular feedback?

Makes macula densa more sensitive, enhances Na-H exchangers and sodium channel functions to promote sodium reabsorption and stimulates thirst and ADH release.

Outline the action of the RAAS when blood pressure is low.

kidney produces renin → liver produce angiotensin I → (angiotensin I→II in lungs) → adrenal gland produces aldosterone → pressure increase

effective circulating volume (ECV)

circulating blood, 5 to 10 litres in volume.

Where are ECV sensors found?

carotid sinus, aortic arch, renal afferent arterioles and atria

efferent pathways controlling the ECV

RAAS, ADH, atrial natriuretic peptide and the sympathetic nervous system

short term ECV effectors

heart and blood vessels

long term ECV effector

kidney. Affects sodium ion concentration

low effective circulating volume

triggers 4 parallel effector pathways which act on the kidney to either change haemodynamics or Na+ transport by renal tubule cells.

Plasma Osmolality

Solute concentration in the plasma, detected by hypothalamic osmoreceptors

Diuretics

indirectly prevent reabsorption of water, typically by preventing sodium ion reabsorption. Short term, usually secondary treatments to offload fluid

sympatholytics

oppose the downstream effects of postganglionic nerve firing in any effector organs innervated by the sympathetic nervous system

Loop Diuretics eg furosemide

Inhibit Na+/K+/2Cl- co-transporter in the loop of Henle

Thiazides (most commonly used)

Inhibit NaCl transporters in the distal convoluted tubule

Potassium Sparing Diuretics

Inhibit distal tubule sodium ion channels or aldosterone receptors.

Renin reaction

Enzyme that acts upon angiotensinogen to produce angiotensin I.

hypertension associated with RAAS

May be partly due to increased angiotensinogen levels. Has around same Km for renin so small changes affect generation of angiotensin I

issue with diuretics

can cause hypokalaemia (loss of potassium ions) → heart issues

Angiotensin-Converting Enzyme (ACE)

Removes 2 carboxy-terminal amino acids from angiotensin I to form angiotensin II.

Aldosterone inhibitors eg spironolactone and eplerenone

competitively bind aldosterone receptors. Promote sodium ion and water excretion in the collecting duct and tubule.

drugs to treat renin-dependent hypertension

antagonistic peptide analogues of angiotensin II and ACE inhibitors eg Captopril

what is the most potent vasoactive substance known?

angiotensin II. Increases blood pressure by causing arteriole vasoconstriction.

angiotensin-renin relationship

angiotensin inhibits release of renin in a short feedback loop

RAAS sensitivity

even small change eg from lying to sitting will increase renin secretion and cause retention of sodium ions and water via aldosterone