Normal physiology

Question 1

Kidney function

Answer 1

By Components

Glomerulus

• podocytes (foot processes)
• filtration / clearance

Juxtaglomerular apparatus

• nephron autoregulation

Tubules

• acid/base balance
• electrolyte balance

By process

Filtration

• GBM filters particles <60kDa (albumin is 66.5kDa, so isn’t filtered unless there’s GBM structural damage; light chains are filtered by re-absorbed)

Secretion

Reabsorption

• light chains are re-absorbed in the PCT (if detected in urine, is a result of excess production)

excretion

Question 2

Body fluid compartments and fluid movement

Answer 2

Water makes up 75% body mass (less in elderly)

Fluid compartments

• ICF (60% or 25L of total body water): within the cells. Cytoplasm. Main electrolytes inc K+, HPO4-, protein.
• ECF (33% total body water): Plasma (20%) and interstitial fluid (also inc peri-visceral spaces e.g. pericardial/pleural). Main electrolytes inc Na+, Cl-, bicarb, protein.

Movement / fluid shift

• Water moves by osmosis, along osmotic gradient, across semi-permeable membrane
• hydrostatic pressure is the force of blood against vessel wall that forces fluid into tissues; in the kidneys it’s the force of fluid in nephrons to ensure filtration /formation of urine
• oncotic (colloid) pressure opposes hydrostatic, mainly from albumin, drawing plasma back into veins

Oedema is accumulation of excess water in tissue, caused by leaky capillaries. (e.g. pedal oedema, pulmonary oedema from CCF, or tissue oedema from reduced oncotic pressure in liver failure)

Hydrostatic oedema results from elevated capillary hydrostatic pressure. Elevated arterial or venous pressure results in higher capillary pressure.

Permeability oedema results from disruption in microvascular membrane.

Lymphoedema is due to impaired lymph drainage, increase lymphatic permeability (leading to protein in the interstitium), obstruction, removal of LN’s.

Question 3

Renal physiology: vascular auto-regulation

Answer 3

Kidney is innervated by sympathetic neurons of the ANS via the celiac plexus and splanchnic nerves.

Reduced sympathetic tone (relaxation) –> leads to vasodilatation (increased renal perfusion).

Increased sympathetic tone (stress) –> leads to norepinephrine release –> subsequent afferent arteriole vasoconstriction + stimulates adrenal medulla –> adrenal medulla then induces further vasoconstriction (of afferent arterioles) via release of epinephrine. Also leads to release of renin which stimulates release of AT-II (vasoconstrictor) and aldosterone (increased Na + H2O retention)

The aim is to redirect blood flow to organs in immediate need.

Auto-regulation:

1. myogenic mechanism
   - works in the afferent arteriole that supplies glomerulus
   - increase in BP causes stretch of Sm muscle aff arterioles –> they respond by contracting to resist the pressure, to prevent changes to flow
   - drop in BP –> less stretch on aff arteriole Sm muscles –> they respond by relaxing to lower resistance allowing continued blood flow
2. tubuloglomerular feedback (involving the juxtuglomerular apparatus and paracrine signalling)
   - macula dense cells respond to changes in flow and Na+ concentration in the DCT (which is in close proximity to the aff/eff arterioles)
   - increase in GFR leads to higher osmolarity in the filtrate (as less time for Na+ reabsorption in PCT), this activates macula densa cells –> respond by releasing ATP + adenosine —> these factors act locally to stimulate the juxtaglomerular cells of the afferent arteriole, leading to vasoconstriction –> subsequently reduces GFR
   - decrease in GFR leads to less Na+ in the urine/filtrate –> leads to less ATP + adenosine formation by macula densa cells –> allows afferent arterioles to dilate –> leads to increase in GFR
   - nitric oxide further relaxes afferent arterioles, and acts to fine tune the constrictive effect of ATP and adenosine on GFR

Source: https://opentextbc.ca/anatomyandphysiology/chapter/25-7-regulation-of-renal-blood-flow/