Renal: Renal Filtration 1

Question 1

three functions of the kidney (brief)

Answer 1

1. primarily an excretory organ
2. maintenance of ECF volume and blood pressure (fluid balance)
3. endocrine functions

Question 2

details about the kidney being an excretory organ

Answer 2

Eliminates byproducts of protein and nucleic acid metabolism (dietary, muscle), drugs, toxins, metabolites.

• BUN - Blood Urea Nitrogen: product of amino acid degradation
• Cr (Creatinine), SDMA (Symmetric Dimethyl Arginine) - Products of muscle and cellular metabolism etc.
• Many other molecules excreted
  -toxins and drugs
  -ketones, sulphates, etc

Question 3

endocrine functions of the kidneys

Answer 3

• Vitamin D metabolism
• Erythropoietin (EPO) production
• Renin-Angiotensin-Aldosterone system (Renin production)

Question 4

what are the vascular components of the kidney

Answer 4

• Glomerulus
• Afferent arteriole
• Glomerular capillaries
• Efferent arteriole
• Peritubular capillary
• Vasa recta

Question 5

what are the tubular components of the kidney

Answer 5

• Bowman’s capsule
• Proximal tubule
• Loop of Henle
• Distal tubule
• Collecting tubule/duct

Question 6

whats part of the juxtaglomerular apparatus

Answer 6

• JGA – afferent and efferent arterioles, mesangial and JG cells, and macula densa – renin release

Question 7

what is the macula densa

Answer 7

is a specialized portion of distal tubular epithelial cells adjacent to JG cells

Question 8

what are the JGA and macula densa important for

Answer 8

Important for control of both systemic and local vascular resistance
(regulation of BP as well as single nephron glomerular filtration rate)

Question 9

what happens in the course of normal metabolism

and why is this important

Answer 9

In the course of normal metabolism, the body generates nitrogenous wastes (urea (BUN), creatinine, SDMA), primarily from protein and nucleic acid metabolism.

Kidneys remove nitrogenous wastes from plasma in direct proportion to the level of renal function – when normal function is present, wastes are rapidly and efficiently removed. When they are sub-functional (disease, injury, lack of blood flow) then clearance is impaired

This is important because:
1) The molecules that accumulate when the kidney is failing are toxic to cells and tissues – leading to clinical disease.
2) The level of these molecules in the blood can be used to assess renal function.

Question 10

what happens in glomerular filtration, what does the glomerulus allow, whats its production, what is estimation of GFR important for

Answer 10

Nitrogenous wastes are removed from plasma by filtration in a structure called the glomerulus.

The glomerulus is a specialized capillary bed which has evolved to allow
– Complete retention of plasma proteins
– Vascular control that permits GFR and renal blood flow to be maintained over wide range of perfusion pressures

Glomerular filtration is the production of a protein-free filtrate of plasma

Estimation/assessment of glomerular filtration rate (GFR) is one of the key steps in the clinical assessment of renal function

Question 11

what is glomerular filtration rate, examples for species

Answer 11

The volume of plasma filtered by all glomeruli in a given time period
* Normal ranges of 2-4 ml/kg/min in a 10 kg dog and 1-3 ml/kg/ min in a 500 kg horse
* 10 kg dog produces 30-60 liters of filtrate every day
* 500 kg horse produces 720-1440 litres of filtrate every day!

Question 12

what do epithelial podocytes do

Answer 12

they put different levels of tension on the filter membrane to let thing pass out or not

they are the most important cell type in glomerular filtration

Question 13

what is glomerular ultrafiltrate

Answer 13

water and small molecules (<2nm) pass freely, cells and larger (<4nm) molecules (proteins) retained = glomerular ultrafiltrate

Question 14

selective permeability of glomerular membrane

Answer 14

• <2 nm (water and small molecules) pass freely
• > 4 nm (larger proteins) retained
• 2-4 nm variable filtration, dependent on electrical charge
  and deformability (-ve charge pass easier than +ve charge)

Question 15

what is glomerulonephritis

Answer 15

• Clinical condition affecting the glomerulus.
• Causes a protein-losing nephropathy of dogs associated with immune-mediated glomerular pathology (immune system damages glomerular membrane)
  – Marked proteinuria (+/- blood)
  – Hypoalbuminemia
  – Peripheral edema
  – Progression to chronic renal failure

Question 16

three factors determining GFR

Answer 16

1. Renal blood flow (RBF) and renal perfusion pressure (PGC ).
2. The net pressure difference between the tubule lumen and the capillaries (balance between blood pressure (“out” of vascular system) and colloidal oncotic pressure (“in” to vascular system).
3. The surface area available for ultrafiltration and the “ultrafiltration
   coefficient” (KUF) of the glomerular membrane

Question 17

what happens to glomerular pressure, renal blood flow and GFR when there is increased resistance in afferent arteriole

Answer 17

all decreased

Question 18

what happens to glomerular pressure, renal blood flow and GFR when there is increased resistance to efferent arteriole

Answer 18

glomerular pressure and GFR increases

RBF decreases

Question 19

what happens to glomerular pressure, renal blood flow and GFR when there is decreased resistance in efferent arteriole

Answer 19

RBF increases
GFR and glomerular pressure decreases

Question 20

what happens to glomerular pressure, renal blood flow and GFR when there is decreased resistance in afferent arteriole

Answer 20

RBF, GFR and glomerular pressure increases

Question 21

what does autoregulation maintain

Answer 21

autoregulation maintains a nearly constant GFR when mean arterial blood pressure is between 80-180mmHg

when blood pressure drops, GFR drops and vice versa

Question 22

what is a myogenic response, and what leads to vasoconstriction vs vasodilation and what is it mediated by

Answer 22

Myogenic response - vascular smooth muscle responses to factors such as adenosine, local hypoxia etc.
* Similar to autoregulation in other systemic arterioles

-increased arterial wall tension = vasoconstriction
-decreased arterial wall tension = vasodilation

Mediated by stretch receptors that open and close ion channels. Modulates blood flow and pressure in the glomerulus and therefore influences GFR. Modulated by local factors (prostaglandins, NO etc.) that are present

Question 23

what are the mechanisms of renal autoregulation (brief)

Answer 23

1- myogenic response

2- hormones and autonomic neurons

Question 24

hormones and autonomic neurons for renal autoregulation… how does it work

what are the hormones for dilation vs constriction

what are the neural factors

Answer 24

Hormones and autonomic neurons - eg. sympathetic vascular responses
* By changing resistance in arterioles (eg. adrenergic receptors)
* By altering the filtration coefficient (tension on the glomerular membrane)

Hormones:
* Vasoconstrictors - Renin-angiotensin-aldosterone system (Angiotensin II), Endothelin
* Vasodilators - Dopamine, Atrial Naturiuretic Peptide/Factor Prostaglandins (PGE2, PGI2)

Neural (ANS) Factors:
* Sympathetic stimulation: Increased vascular resistance
and increased renin release.

Question 25

renin angiotensin aldosterone system (how it affects BP, ADH secretion, tubular reabsorption, sympathetic activity)

Answer 25

a decrease in renal perfusion (decreased blood pressure), leads to release of renin which immediately activates angiotensinogen to angiotensin. angiotensin converting enzyme then activates it into angiotensin 2 which has many effects:
1= effects on arteriole vasoconstriction that would increase blood pressure
2 = angiotensin 2 stimulates the pituitary gland and causes ADH secretion which stimulates the collecting duct for water absorption
3 = stimulate adrenal gland to secrete aldosterone
4 = directly increase tubular Na, Cl reabsorption and K excretion, water retention (aldosteron also does this)

*** if BP is too high, the opposite happens