Renal Function/Dynamics Glomerular Filtration (Day 1) Flashcards Preview

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1

Functions of Kidney

  • Regulation of Water and Electrolyte Balance
  • Excretion of Metabolic Waste
  • Excretion of Bioactive Substances
  • Regulation of Arterial Blood Pressure
  • Regulation of Red Blood Cell Production
  • Regulation of Vitamin D Production
  • Metabolism

2

What metabolic wastes do the kidneys excrete?

 

  • Urea (from proteins)
  • Uric Acid (from nucleic acids)
  • Creatinine (from Muscle creatine)
  • Hemoglobin breakdown products
  • Metabolites of various hormones (from endocrine system)

Our bodies continuously form end products of metabolic process.

  • In most cases these end products serve no function and are only harmful at high concentrations

3

How do the kidneys regulate BP?

  • Blood pressure depends ultimately on blood volume
    • Kidneys' maintenance of Na and H2O balance achieves regulation of blood volume
  • Kidney releases renin from juxtaglomerular cells, acts on angiotensinogen (released by liver) to form angiotensin I
  • Angiotensin I is converted by ACE (mainly by lung, but also renal endothelium) to angiotensin II
  • Angiotensin II acts on:
    • SNS
    • Tubular absorption Na, Cl and K excretion. H2O retention
    • Increase Aldosterone
    • Arteriolar vasoconstriction to increase BP
    • Pituitary gland ADH secretion--> collecting duct H2O absorption

4

How do the kidneys regulate RBC production?

 

  • Erythropoietin is released by the kidney and controls erythrocyte production by the bone marrow
    • Secretion is regulated by the partial pressure of oxygen in the kidneys

 

5

How does kidney regulate Vitamin D production?

 

  • Skin exposed by UV radiation (7-dehydrocholesterol--> Cholecalciferol (Vitamine D3)
  • changed by liver to (25-dyroxyvitamin D3)
  •  and then by kidney to (1,25- dihydroxyvitamin D3)--> maintain calcium balance in body
  • 10-15 min exposure needed 2x/week

6

Why do you need Vitamin D? 

To absorb Calcium

7

What are some roles kidney plays in metabolism?

  • Glyconeogenesis (from amino acids and glycerol)
  • Renal ammonioagenesis (maintains acid-base balance)

8

What are the 2 main segments in the kidney?

  • Cortex- function area (outside portion)
    • Area where we actually do things
    • Area of cortex extends into renal columns
    • Cortex is where we have glomeruli and majority of nephrons
    • Bigger need for cortex vs medulla
      • Why we have extensions everywhere in the kidney
  • Medulla- collecting system (inside)
    • Collecting urine as we create it
    • As renal columns extend into medulla, breaks medulla into smaller pieces called renal pyramids

9

What is the renal papilla? Where is it?

Where we have final urine created.

It is located at top of renal pyramids

10

What is the renal pelvis?

  • Most dilated area of kidney narros to become ureter--> bladder

11

Pathway of urine from renal papilla?

Renal papilla--> minor calyx--> major calyx--> renal pelvis--> ureter

12

What is the renal corpusle?

Renal corpuscle= bowman's capsule and glomerulus

  • Compact tuft of interconnected capillary loops
  • Surrounded by a balloon-like hollow capsule (bowman's capsule)
  • Blood enters and leaves Bowman’s capsule through arterioles
  • A fluid-filled space exists within the capsule
  • This functions to filter the blood

13

Where is the kidney?

What enters/exits kidney?

What sits on top of kidney?

 

  • Kidney is retroperitoneal organ
  • Upper part of abd (one portion covered by ribs and portion not)
  • Adrenal gland on top of kidney
  • Each kidney has one artery to them and one vein that exits.

14

What is a nephron?

  • Nephron- one cell thick tubes, functional unit of kidneys
    • Different segment nephron, different function
    • Heterogenous
    • Mostly cortex nephrons (short nephrons, 80%), some medulla (longer nephrons, 20%)

 

  • The nephron is very compact
    • Loop of henle and collecting duct= medulla
    • Corpuscle/distal tubule= cortex

15

What is the proximal tubule?

  • Drains from Bowman’s capsule
  • Consists of two segments, the proximal convuluted tubule and the proximal straight tubule
  • Majority of reabsorption happens here

 

  • Don’t need to differentiate within proximal tubule
  • 60-70% reabsorption happens in proximal tubule
    • Remainder (~30%) in distal tubule

16

What is the loop of henle?

  • Made up of descending thin limb, ascending thin limb, and the thick ascending limb
  • Functions to create and maintain a medulla osmotic gradient
  • Macula Densa demarkes the area between the Loop and the Distal Tubule

17

What is the distal tubule?

  • Only the distal convoluted tubule
  • Functions as continued area of reabsorption and regulation
  • Where rest of absorption happens
  • Looks at Na levels, and changes how much volume needs to be reabsorbed for needs of body at that time

18

What is the collecting duct?

  • Last portion of an independent nephron
  • Functions as the concentrating mechanism of the nephron

 

  • Collecting duct uses gradient created by loop of henle
  • Function is to determine concentration and dilution of urine
  • Does this by responding to hormone called ADH (anti-diuretic hormone, also called vasopressin)

19

What is ADH?

  • ADH  (anti-diuretic hormone or vasopressin) opens up water channels on collecting ducts which allows water to be reabsorbed into blood stream
    • More water reabsorbed, more blood volume you have and higher BP
    • Concentrates urine as it draws water out of urine

20

What are cell types like in the nepron before the distal tubule?

Homogenous, all same cell types

21

What are the 2 cell types present in the distal tubule?

  • Principal cells (primary cell type)
  • Intercalated cells (acid/base cells)
    • Actually two kinds (alpha and beta)

22

What is the juxtaglomerular apparatus?

  • Juxtaglomerular cells- release renin
    • In between distal tubule and afferent arteriole
  • Macula densa cells in between distal tubule
    • Function as sensory cells. Detect level of Na in plasma
    • Also sense drop in amount of filtration happening
    • Indication that we need to increase the amount of filtration happening
    • Sense low flow, and stimulate juxtaglomerular cells to secrete renin. Renin will then be released into blood stream, go to glomerulus

23

What is important about the loop of henle?

Creates the osmotic gradient necessary in order to reabsorb solutes

24

What type of nephron creates the largest gradient?

Juxtamedullary nephron (longest loop of henle)

25

What is blood flow into and out of glomerulus?

Afferent arteriole--> glomerulus--> efferent arteriole

26

Where does blood go from efferent glomerulus?

  • Depends on type of nephron
    • Cortical nephron: peritubular capillaries
    • Juxtagmedullary: goes to vasa recta

27

How much cardiac output goes to the kidney?

20% ~1L/min

28

What is blood flow from renal artery? (unsure if we have to know all of this...)

  • Renal artery
  • interlobar arteries
  • arcuate arteries
  • interlobular (cortical radial arteries)
  • afferent arteriole (site of regulation)
  • glomerular capillaries
  • efferent arteriole (NOT venule)
  • peritubular capillaries (only if cortical nephron, otherwise goes to vasa recta)
  • venule
  • veins

29

What are peritubular capillaries?

  • Peritubular capillaries extend from cortical efferent arterioles and are profusely distributed throughout the cortex

30

What are vasa recta?

  • From the juxtamedullary glomeruli, long efferent arterioles extend downward into the outer medulla, where they divide many times to form bundles of parallel vessels called the vasa recta

31

What is renal plasma flow?

  • Whole blood enters the glomerulus, but only plasma is filtered by the glomerular capillaries.
  • Since RBCs aren’t normally filtered, the RPF is the RBF, less the contribution of the hematocrit HCT
    • RPF=RBF*(1-HCT)

32

What is filtration?

  • Filtration:  the process by which water and solutes leave the vascular system through the filtration barrier and enter Bowman’s space

33

What is secretion?

  •  the process of moving substances into the tubular lumen from the cytosol of epithelial cells that form the walls of the nephron

34

What is reabsorption?

  • the process of moving substances from the lumen across the epithelial layer into the surrounding interstitium
    • In most cases the reabsorbed substances then move from the interstitium into surrounding blood vessels (two step process)

35

What is excretion?

exit of the substance from the body (ie the substance is present in the final urine produced by the kidney)

36

What is synthesis?

  • substance in construction from molecular precursors

37

What is catabolism?

 

the substance is broken down into smaller component molecules

38

What percentage of the blood entering the kidney flows directly into the medulla without passing through the cortex?

0% All blood must flow through the cortex before it enters the medulla

39

Substance T is present in the urine.  Does this prove that it entered the renal tubule by filtration at the glomerulus?

No, substance T could have been secreted 

40

A substance is filtered into Bowman’s space and excreted in the urine.  How many cell membranes must it cross in order to exit the body?

0

No cellular membranes are crossed in the glomerulus.  Substances must pass through tight defined spaces, but not across any cellular membranes.

41

A substances is freely filtered.  Does this mean that it is all filtered?

No, Freely filtered means that there is no barrier to its ability to be filtered.  Therefore any substances that is freely filtered will show up in the tubule at the same concentration as it appears in the plasma.

42

If you labeled cells of the macula densa, where would you find the label?

Cortex only, The macula densa cells are only found connected to the glomerulus.  All glomeruli are found in the cortex. 

43

What is general equation to determine excretion?

Excretion= filtration +secretion- reabsorption

44

What are the characteristics of glomerular filtrate (specifically in relation to blood)?

  • The glomerular filtrate is very much like blood plasma, however, it contains very little total protein
    • Consists mainly of inorganic ions and low-molecular-weight organic solutes in virtually the same concentrations as in the plasma.

45

What is plasma?

Blood, spun down, bottom is HCT and top is plasma. Makes up ISF

46

What substances are freely filtered?

  • Many low-molecular-weight components of blood are freely filtered
    • Ions (Na, K, CL, HCO3)
    • Neutral organics (glucose and Urea)
    • Amino acids
    • Peptides (insulin and ADH)

47

What is GFR?

  • The volume of filtrate formed per unit time=GFR
    • 180L/day (normal 100- 125ml/min)

48

What allows the kidney to filter?

Presence of smooth muscle on both sides of glomerulus

49

What 3 things make up the barrier in the glomerulus?

  • Endothelial Cells
  • Podocytes
  • Mesangial cells

50

What is the role of the endothelial cells in glomerulus?

  1.  line blood vessels (capillary cells)
    1. There's little space between all endothelial cells (called fenestration space) too small for cells and proteins to get through
    2. SIZE of fenestrations is how capillaries help keep things out

51

What is the role of podocyte cells?

  • "Foot cells"
  • Podocytes: cells that are around glomerulus; squeeze and create split space and things have to fit through to get out
  • SIZE

52

What is the role of mesangial cells?

  • Creates basal membrane
  • Modified smooth muscle cell
    • can also contract and decrease SA in glomerulus
  • Sits inside glomerulus, lays down extra-cellular matrix called glomerular basement membrane
  • Highly negatively charged; this is important because normal charge for proteins floating through blood? Negative, so the basement membrane repels them
  • Keeps things out based on CHARGE!

53

What are the forces favoring filtration?

  • HPC: 45mmHg
  • πBS: 0

54

What are the forces opposing filtration?

  • HPBS:10mmHg
  • πC: 25 mmHg

55

What is the general amount of pressure driving filtration through glomerulus?

  • 10mmHg is overall pressure that causes net filtration
  • Blood pressure determines net filtration: what happens in blood pressure drops 10mmHg? stops! Narrow window today determine filtration
  • Blood pressure is ESSENTIAL for kidney to have filtration

56

Equation for NFP?

  • NFP= (PGC - PBC - πGC)

57

What is the equation for GFR?

  • GFR= Kf *(PGC - PBC - πGC)

58

What is Kf? What is it's relationship to GFR?

  • Can be changed by glomerular disease and drugs.
  • Unknown messengers can also cause mesangial contraction, restricting flow through some of the capillary loops, reducing area available for filtration (decreasing Kf=decreased GFR)
  • Kf can be changed by renal dx
  • Kf  decrease and GFR decrease
  • Donate kidney, GFR decreases by ½
  • Some drugs cause smooth muscle contraction, causing mesangial cells to constrict
    • decrease size of glomerulus, decrease Kf, and  decrease GFR

59

What is HPbs?

hydrostatic pressure- bowman’s space

  • Changes in this variable are of very minor physiological importance
  • Obstruction anywhere along the tubule or in the external portions of the urinary system can increase hydrostatic pressure in Bowman’s capsule
    • Decreases GFR

 

  • HPbs comes from fluid/tissue in bowman’s space
  • Generally very constant
  • Only time is changes is when you have obstruction in nephon (i.e. kidney stone) fluid backs up inside nephron/bowman’s space and then ­increase HPbs, causing GFR to decrease

60

What is HPgc

(hydrostatic pressure- glomerulas capillary)

HPc: only favoring force for filtration!

  • Not by much; 10mmHg; this is very important it need to stay nice and high!
  • The reason why glomerulus can filter is smooth muscle on both sides

61

What happens to GFR is you vasoconstrict afferent?

Vasoconstric efferent?

  • Vasoconstriction of afferent: HPc will decrease because not as much blood to glomerulus, decrease GFR (less pressure)
  • Vasoconstrict efferent:  increase HPc ­, increase GFR ­(more pressure)

62

What happens if you dilate afferent artiole?

Efferent arteriole?

  • Dilation Afferent: allows for more blood to come in, increase ­Hp and ­ increase GFR
  • Dilation Efferent: dilate will decrease HP which will  decrease GFR

63

What combination of vasoconstriction/vasodilation will cause most increase in GFR?

increase GFR by dilating afferent and constrict efferent

 we have receptors to differentially do this based on what body needs

64

What is oncotic pressure of the capillaries?

  • A decrease in arterial plasma protein concentrations will lower arterial oncotic pressure and increase GFR
  • Anything that causes a steeper rise in oncotic pressure will tend to lower filtration pressure and hence GFR
  • Opposes filtration

  • changed with  decrease in protein (i.e. liver failure)
    • πc will decrease causing ­increase in GFR
  • Any increase in πc will decrease GFR (­RBC, polycythemia)

65

What is filtered load?

  • The amount of substance that is filtered per unit time
  • Freely filtered substances:
    • GFR*Plasma concentration
  • For example: Na
    • 125 ml/min * 140 mEq/L = 17.5 mEq/min.
    • Filtered load is what the rest of the nephron has to handle

66

What are 2 ways kidney does autoregulation?

Tubuloglomerular feedback

Myogenic response

67

What is the myogenic mechanism?

  • acute changes in BP
  • BP too high dilates, too low, constricts
  • short term regulation

68

What is tubuloglomerular feedback?

  • Also called juxtaglomerular feedback
  • If flow too low, work to ­GFR by ­ increasing renin. Then ­increase BP to increase ­HPc to ­increase GFR
  • If distal tubular flow or osmolarity is high, TGF will increase afferent arteriolar resistance, decreasing GFR.

  • These systems (myogenic and tubuloglomerular feedback) allow minute-to-minute regulation of GFR over a wide range of systemic blood pressures (MAP 80 to 180 mm Hg).