Kidney

Question 1

Describe how the filtration barrier of the kidney is specialised to create an ultrafiltrate of plasma.

Answer 1

1. Fenestrated capillaries – high filtration rate but its red blood cells (plasma) can go through
2. Basement membrane – gel like - help select what can cross the filtration barrier based upon molecular weight and electrical charge.
   Collagen fibres and glycoproteins (glycoproteins being negatively charged). The negatively charge glycoprotein repel the negatively charge protein (albumin)
   preventing them to pass through.
3. Podocytes – wrap around glomerular capillaries to create a barrier which prevents filtration of cells and proteins.

Question 2

Describe the process of isosmotic fluid reabsorption in the proximal tubules.

Answer 2

Proximal tubules are lined with simple cuboidal epithelium and have microvilli which increase SA for reabsorption.
Contents in PCT are reabsorbed into bloodstream from luminal membrane through basolateral membrane to peritubular capillaries.

Two routes it can occur through transcellular and paracellular.

Transcellular – transport solutes through a cell (requires both luminal and basolateral membrane) to be permeable.
Paracellular – transports between cells through intercellular space

Na+ is the most important as it helps with the reabsorption of other solutes (lactate, amino acids, phosphate and citrates)
It can move through cotransporters such as (Na-Glucose) (SGLT2), Glucose can then move through GLUT1 and GLUT2 via passive transport into the bloodstream.

3 Na+ is moved out of the basolateral membrane and 2K+ move in through ATPASE.
So, Na+ is left low in interstitial cell so Na+ can carry on moving in

Fewer Claudin proteins so leaky junctions so paracellular transport can occur such as Cl- reabsorption.
Reabsorption of NaCl through paracellular reabsorption can create osmotic gradient for water reabsorption as well

Question 3

Describe how changes in plasma osmolarity can results in changes in urine composition.

Answer 3

Osmoregulation is the regulation of body fluid solute concentration.
If there is a change in osmolarity then negative feedback is undergone

The change is osmolarity is detected by osmoreceptors found in OVLT and SO (outside the blood brain barrier).
Neurones sent to posterior pituitary (parturition and peeing)

Increase in osmolarity (less fluid) = dehydration so detected and neural signals are sent to hypothalamus causing more ADH to be produced.
Kidney responds

Collecting duct is impermeable to water and urea. ADH travels through peritubular capillaries and binds to V2 receptors on the basolateral membrane, phosphorylation of protein kinase A, vesicles fuse to membranes and exocytosis occurs so more permeable, as aquaporins attach to the luminal membrane. As solute concentration is high water moves through osmotic gradient (290 mOsm/L to 600 mOSm/L)

Aquaporin 3 and 4 are always present regardless of ADH presence.

More water in body means aquaporins do not attach as less ADH so H2O is removed instead

Question 4

Explain the role of counter current multiplication and urea in creating highly-concentrated urine

Answer 4

Electrolytes (NaCl) move into the interstitum making urine more dilute in ascending loop (hyperosmotic)
Creates a osmotic gradient so water moves in from thin descending loop into interstitum – isotonic
Increases NaCl of the tubular fluid in thin descending limb
Travels around apex to thick ascending limb
More NaCl can get pumped in

Question 5

Explain how urine flow rate is increased in Fanconi’s syndrome, Diabetes Mellitus and Diabetes Insipidus.

Answer 5

Diabetes Insipidus (DI)
Disease presenting polyuria (urinate more than normal) and polydipsia (excessive thirst)
Two types:
Neurogenic DI – posterior pituitary does not produce ADH
Nephrogenic DI – genetic mutation, inherited defect where collecting duct does not respond to ADH

Fanconi’s Syndrome – failure of the proximal tubule reabsorption
So more solutes are lost hence higher urine flow rate

Diabetes Mellitus –
Caused due to high blood sugar levels
High blood sugar levels causes more glucose in kidneys so leave urine; glucosuria
Increasing urine flow rate

Question 6

What does NSAIDs and Empagliflozin do?

Answer 6

Empagliflozin blocks SGLT2 - this is used to treat type 2 diabetes as it can lower blood glucose as it blocks glucose reuptake in PCT

NSAIDS - anti inflammatory drugs inhibit COX1 and COX2. Prostaglandins cause vasodilation of afferent arterioles increasing GFR. NSAIDs inhibit the role of COX enzymes, reduces prostaglandins and so loss of afferent arteriole vasodilation, less GFR.