SUGER Flashcards
What is mendelian genetics?
Fault in a single gene
Rare
What is complex trait genetics?
Changes in lots of genes
Common
E.g. diabetes, asthma
What is somatic genetics?
Any alteration at the cellular level in somatic tissues occurring after fertilization
E.g. cancer
What is ADPKD?
Autosomal dominant polycystic kidney disease (ADPKD) is an inherited condition that causes small fluid-filled sacs called cysts to develop in the kidneys
What is autoregulation in the kidney and what are the 2 mechanisms?
Maintains constant GFR and excretion of water and waste products
Tubuloglomerular feedback
Myogenic mechanism
How does tubuloglomerular autoregulation work?
Increase in BP
Increase in blood flow to glomerulus and pressure
Increases GFR (more filtration and delivery NaCl to macula densa)
Afferent arteriole contraction to reduce blood supply to glomerulus
Decrease BP = afferent arteriole vasodilation to increase blood supply to glomerulus
How does the renin-angiotensin-aldosterone system work?
(tubuloglomerular)
Renin stimulates Angiotensinogen to angiotensin 1 to angiontensin 2:
- Increase sympathetic activity, excrete more NaCl and K
- Secrete aldosterone and ADH
Water and salt retention
Negative feedback to juxtaglomerular apparatus
How does the myogenic reflex work when BP increases? (only in pre-glomerular resistance vessels)
Increase bp stretches wall
Opens stretch-activated cation channels
Membrane depolarisation
Opens voltage-dependent calcium and intracellular calcium increases
Smooth muscle contracts
Increases vascular resistance
Minimises change in GFR
What makes up the filtration barrier?
Fenestrated capillary endothelium
Glomerular basement membrane (charged)
Podocytes (visceral epithelium)
Filtration slits and slit diaphragms
What is the juxtaglomerular apparatus?
Modified muscular layer of afferent arteriole
Juxtaglomerular cells and macula dense
Located in the hillum of every glomerulus
What is the arterial supply of the kidneys?
Abdominal Aorta
Renal artery
Interlobar artery
Arcuate artery
Interlobular artery
Afferent arteriole
Glomerular capillary
How does blood drain out of the kidneys after the glomerulus?
Efferent arteriole
Peritubular capillaries
Vasa recta
Interlobular veins
Arcuate veins
Interlobar veins
Renal vein
IVC
What makes up the nephron?
Blood vessels
Glomerulus
Bowman’s capsule
Proximal convoluted tubule
Loop of Henle
Distal convoluted tubule
Collecting duct
What is the function of the kidneys?
Removal of waste products
Removal of excess fluids
Balance salt, water and pH
Control of blood pressure
RBC production
Factors determining which molecules can get through the filtration barrier?
Pressure
Size of the molecule
Charge of the mulecule
Rate of blood flow
Protein binding
What makes up the kidney?
Capsule
Medulla
Cortex
Adipose tissue
How does pressure affect filtration?
Favours filtraion: glomerular capillary bp
Opposes filtration: fluid pressure in Bowman’s space, osmotic forces in the protein and plasma (pulling water back)
How does size affect filtration?
Small molecules and ions up to 10kDa can pass freely (glucose, uric acid, potassium, creatinine)
Larger molecules restricted (plasma proteins like albumin)
How does charge affect filtration?
Glomerular basement membrane has a fixed negative charge so repels negatively charged ions (albumin)
Neutral or positive molecules can get through easier
How does rate of blood flow affect filtration?
GFR higher with lower flow in afferent
GFR lower with really high flow (peaks in the middle) in efferent
How much urine is produced?
1ml per minute
How does protein binding affect filtration?
Bound to protein more likely to stay within system
Filter fluid usually protein free
Affects drugs, calcium, thryoxine
What causes nephrotic syndrome?
Damage to filtration barrier causing protein leaking (albumin, clotting cascade, infection defence)
Main cause is diabetes
What is glomerular filtration rate?
filtration volume per unit time (minutes)