2.1 The Glomerulus And Glomerlar Injury Flashcards

1
Q

What is reabsorption?

A

the movement of a substance from the tubular fluid back into the circulation

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2
Q

What is secretion?

A

the movement of substances from the blood into the tubular fluid via tubular cells (active transport) or intracellular spaces (passive transport)

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3
Q

What is excretion?

A

the removal of waste products from the blood and the net result of filtration, secretion and reabsorption of a substance

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4
Q

What 2 ways can solutes be transported across cells?

A
  1. Paracellular movement – across the tight junctions connecting the cells. Down concentration gradient
    2 Transcellular movement – through the cell. May be down or against concentration gradient. Water follows movement of solutes by osmosis
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5
Q

What is diffusion?

A

The movement of a substance down their electrochemical gradient. Passive. Must be lipid soluble

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6
Q

What is facilitated diffusion?

A

The movement of a substance down their electrochemical gradient, relies on a carrier molecule to transport substances across the membrane. Passive. Faster than diffusion. Relies on a pore, channel or carrier protein.

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7
Q

What is primary active transport?

A

energy dependent process in which substances cross the cell membrane against their concentration and electrochemical gradients.

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8
Q

How is energy for primary active transport attained?

A

hydrolysis of ATP to ADP and Pi to provide chemical energy for the transport mechanism.

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9
Q

What is the most important primary active transporter?

A

Na +/K+ ATPase pump. Found on the basal and basolateral membranes of the tubular cells

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10
Q

What are tubular cells?

A

Cells that line the convoluted tubule

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11
Q

Give examples of primary active transporters?

A

Na+/K+ ATPase
Ca 2+ ATPase
H+/K+ ATPase
H+ ATPase

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12
Q

What is secondary active transport?

A

Transport that uses the energy produced from another process for transporting molecules.

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13
Q

What is a symporter?

A

A membrane channel protein that is a secondary active transporter. Moves a molecule in the same direction as Na + gradient
e.g. Na+/K+ cotransporter or Na+/glucose

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14
Q

What is an antiporter?

A

A membrane channel that is a secondary active transporter. Move ions against electrochemical gradient, opposite to Na+ gradient
e.g. Ca2+/Na+ and the H+/Na+ exchangers

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15
Q

Give examples of primary active transporters?

A
  • H+/K ATPase
  • Proton pump
  • Ca2+ ATPase
  • Na+/K+ ATPase
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16
Q

What are ion channels?

A

Protein pores found on the epithelial cell membranes.

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17
Q

What ion channels are found in the kidney?

A

Channels specific to Cl -, Na+ and K+ are found on apical membrane of tubular cells.

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18
Q

How many L a day are excreted?

A

1.5L

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19
Q

How can we work out the total body fluid?

A

60% of weight (42L in average 70kg man)

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20
Q

Describe the distribution of total body water

A
1/3 is extracellular fluid
- 3/4 is interstitial fluid
- 1/4 intravascular/plasma 
2/3 is intracellular fluid 
- 2L in RBC
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21
Q

Describe the composition of blood?

A

5.5L of blood
2L of water in RBC
3.5L of plasma

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22
Q

Describe the intracellular composition of ions

A

high K+, low Na+, many large organic anions

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23
Q

Describe the composition of extracellular fluid

A

low K+, high Na+, main anion Cl- and HCO3-

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24
Q

How is the difference in ion composition of intracellular and extracellular fluid maintained?

A

By active transport (Na+/K+ ATPase)

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25
Q

What is osmolality?

A

is solute per kilogram of solvent

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26
Q

What is osmolarity?

A

number of osmoles of solute per litre

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27
Q

What is oncotic pressure?

A

osmotic force due to proteins

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28
Q

In what units are oncotic pressures measured?

A

In milli-osmoles

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29
Q

What cannot be filtered out of the glomerulus normally?

A

blood cells and platelets

proteins

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30
Q

Where is the glomerulus found?

A

In the cortex

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31
Q

What is the normal GFR?

A

90 - 120 ml/min

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32
Q

What is the renal plasma flow?

A

800mL/min

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33
Q

What is the filtration fraction?

A

proportion of fluid reaching the kidneys that passes into the renal tubules
GFR-RPF (renal plasma flow)

34
Q

How do DCTs appear different to PCTs on microscopy?

A

DCT have thinner tubule cell walls.

PCT have a less clear lumen

35
Q

What is a fenestration?

A

A gap between endothelial cells of the glomerulus

36
Q

What is a filtration slit?

A

A gap between the podocyte processes (pedicels) surrounding the endothelium

37
Q

How are podocytes adapted to enable selectivity?

A

Podocyte processes are negatively charged to repel negatively charged ions in blood, stopping them from entering filtrate.

38
Q

Why are haemoglobin and serum albumin unable to be filtered?

A

As their molecular weight is too large

39
Q

Why do many disease processes cause proteinuria?

A

As they cause the negative charge on the filtrate barrier to be lost. This allows proteins to be filtered through the filtration slits more easily as they arent repelled.

40
Q

What is the difference between microscopic and macroscopic haematuria?

A
Microscopic = not visible, only detected on further investigations/ under microscope
Macroscopic = blood causes changes in urine colour
41
Q

What is the main driving force of fluid in the renal corpuscule?

A

Hydrostatic pressure in the glomerular capillary, drives fluid out of the capillary into the bowmans capsule.

42
Q

What forces contribute towards filtration at the glomerulus?

A

Hydrostatic pressure in the capillary
Hydrostatic pressure in the Bowman’s capsule
Oncotic pressure difference between
the capillary and tubular lumen - caused by proteins in blood exerting on osmotic pressure

43
Q

How is renal blood flow and glomerular filtration rate regulated?

A

Auto regulation

  • myogenic mechanism
  • tubuloglomerular feedback
44
Q

Describe the mechanism of myogenic regulation

A

Arterial smooth muscle responds to increases and decreases in vascular wall tension. Very rapid (3-10sec).
Predominantly occurs in pre-glomerular arterial vessels ( arcuate, interlobular, afferent arteriole)

45
Q

How does the myogenic regulation react to increases and decreases in renal blood flow?

A

Increased BP: vasoconstriction at the afferent arterial to decrease the GFR
Decreased BP: vasoconstriction at the efferent arterial to increase the GFR

46
Q

Describe the mechanism of action of tubularglomerular feedback

A

Links sodium and chloride concentration at the macula densa with control of renal arteriolar resistance.
Macula densa cells of the DCT epithelium detect osmolality of filtrate
The higher the flow of filtrate the higher the Na+ concentration in cells.
The macula densa cells can send a signal to the juxtaglomerular cells, to trigger a change in smooth muscle tone of the afferent arteriole to maintain RBF and GFR

47
Q

How does the juxtaglomerular feedback regulation react to increases and decreases in blood pressure?

A

Increased BP: high concentration of sodium detected. Detected by macula densa cells in DCT. Signal (ATP) is sent from macula densa cells to juxtaglomerular cells. Vasoconstriction of the afferent arteriole.

Decreased BP = less sodium detected in filtrate at the DCT. Macula densa cells release prostaglandins which reduces the constriction of the afferent arteriole that has been caused by systemic vasoconstriction. Renin produced by the juxtaglomerular cells ( sympathetic nerve stimulation, decreased signals from macula dense and decreased stretch of the afferent arteriole

48
Q

What 3 stimuli cause the juxtaglomerular cells to release renin?

A
  • Sympathetic nerve stimulation (systemic contraction)
  • ↓ stretch of afferent arteriole
  • Signals generated by macula densa cells in response to ↓NaCl delivery (lack of ATP signals)
49
Q

Why is renin released by the juxtaglomerular cells when BP drops?

A

Renin causes angiotensinogen to be converted into angiotensin 1. In lungs, angiotensin 1 converted to angiotensin 2. Angiotensin 2 affects the efferent arterioles, causing constriction. Constriction of the efferent arteriole causes back up of blood in the glomerulus, increasing hydrostatic pressure and GFR. Angiotensin 2 also increases the aldosterone produced by the adrenal glands, so more sodium can be reabsorbed at the distal convoluted tubule, increasing water reabsorption and BP.

50
Q

Why should a patient at risk of poor renal perfusion not be put on NSAIDS?

A

NSAIDS stop the juxtaglomerular cells from producing prostaglandins. Therefore if their BP drops, systemic vasoconstriction will be activated and the dilation of the afferent arteriole will not occur. Patient is at risk of acute renal failure.

51
Q

What is the action of ACE inhibitors?

A

Act to stop angiotensin 1 being converted to angiotensin 2 in the lungs. Means that constriction of the efferent arterioles cannot occur to increase GFR. Useful for patient to reduce BP, esp in diabetic nephropathy. Helps maintain kidney function.

52
Q

What are the 3 different classifications of glomerular disease?

A
  • Hereditary
  • Primary (most common): disease process originates from the glomerulus
  • Secondary to systemic diseases: e.g. systemic lupus erythematosus (SLE), diabetes mellitus, bacterial endocarditis
53
Q

What is glomerularnephritis?

A

Inflammation of the glomerulus

54
Q

What structures in the glomerulus are prone to damage?

A
  • Capillary endothelial cell lining
  • Glomerular basement membrane
  • Mesangium supporting the capillaries
  • Podocytes on the outer surface of the capillary
55
Q

How is nephrotic syndrome characterised?

A

Proteinuria (typically >3g/d).
• Hypoabluminaemia. Sufficient to cause
• Oedema
• Hyperlipidaemia (increased hepatic lipoprotein synthesis secondary to protein losses)

56
Q

How does albumin enter the filtrate in nephrotic syndrome?

A

increased permeability of the glomerular filter to albumin as a result of glomerular basement membrane damage and increase in pore size.

57
Q

How is nephrotic syndrome managed?

A
  • Blood pressure control
  • Reduction in proteinuria using ACE inhibitors
  • Control of hyperlipidaemia
  • Anticoagulation if hypercoaguable (risk of thrombosis increases as albumin decreases)
  • Treatment of underlying cause where possible
58
Q

What is the leading cause of end stage renal disease?

A

Diabetic nephropathy

59
Q

Describe the pathological changes that occur in the glomerulus in diabetic nephropathy

A

Excess glucose in blood binds to proteins. Especially at efferent arteriole. Glycosylation of the BM of the efferent arteriole obstructs blood flow, increases pressure in the glomerulus (Hyaline arteriosclerosis)
Initially increased GFR (hyperfiltration)
High pressure state causes mesangial cells to secrete more structural matrix. This can cause Kimmelstiel-Wilson nodules.
Deposition of matrix causes thickening of BM, enlarging the filtration slits and increasing glomerular permeability
Damage to the glomerulus and nephron eventually causes decrease in GFR and albinuria

60
Q

How is diabetic nephropathy treated?

A

Hypertension
good glycemic control
ACE inhibitors
angiotensin receptor blockers

61
Q

Give examples of nephrotic conditions?

A

Diabetic nephropathy
Minimal change disease
Membranous glomerulonephritis
Focal segmental conditions

62
Q

What is minimal change disease?

A

Most common cause of nephrotic syndrome in children under 6. Proteinuria. No significant renal changes are seen under light microscope. Prognosis good in children, variable with adults.

63
Q

What is membranous glomerulonephritis?

A

Subepithelial deposition of immune complexes (between BM and podocyte). Thickening of BM. 40% adult nephrotic syndrome. Thickening leads to big leaky pores allowing protein to be filtered.

64
Q

What are the causes of membranous glomerulonephritis?

A

idiopathic (85%)
primary or secondary; infections (syphilis, malaria, hep B), tumors, drugs (heroin, mercury), systemic illnesses (systemic lupus erythematosus)

65
Q

How is membranous glomerulonephritis treated?

A

immunosuppressants

treatment of underlying cause

66
Q

What is focal segmental glomerulosclerosis?

A

Damaged podocytes. Proteins build up in glomerulus – hyalinosis (glassy) – leading to sclerosis and scarring of glomerulus . Disease only affects some glomeruli (segmental) not all.

67
Q

What causes focal segmental glomerulosclerosis?

A

Primary: Idiopathic
Secondary: Sickle cell disease, HIV, heroin abuse, kidney hyperperfusion

68
Q

How is focal segmental glomerulosclerosis treated?

A

Steroids.

Inconsistent results can lead to chronic renal failure

69
Q

What are the symptoms and signs of acute nephritis syndrome?

A
  • Oliguria/anuria
  • Hypertension
  • Hematuria – microscopic or macroscopic

• Fluid retention – seen as facial oedema
• Uraemia
• Proteinuria
Also loin pain, headaches, and general malaise.

70
Q

How are nephritic syndromes treated?

A

Steroids

71
Q

Give examples of nephritic conditions? (4)

A

IgA nephropathy (berger’s disease)
Rapidly Progressive Glomerulonephritis
Post-streptococcal glomerulonephritis
Goodpasture’s Syndrome

72
Q

What is IgA nephropathy?

A

Hypertension and IgA levels raised. Deposited in mesangium. Sclerosis of damaged segment. High risk of developing CKD

73
Q

What is the most common primary glomerular disease worldwide causing recurrent haematuria?

A

IgA nephropathy

74
Q

How is IgA nephropathy treated?

A

control BP
antihypertensives
steroids

75
Q

What is rapidly progressive glomerular nephritis?

A

Sever glomerular injury. Leakage of fibrin from BM, macrophages and epithelial cells proliferate. Crescent shape masses form. Reducing glomerular blood supply. Loss of renal function within days to weeks.

76
Q

How is recurrent progressive glomerulonephritis treated?

A

high dose steroids
immunosuppressants
plasma
exchange

77
Q

What is post-streptococcal glomerulonephritis?

A

Presents 1-3 weeks following group A -hemolytic streptococcal infection of tonsils, pharynx or skin.

78
Q

What is the treatment of post-streptococcal glomerulonephritis?

A

antibiotics to treat remaining infection
Prognosis excellent in children
~60% adults recover completely, the rest develop hypertension or renal impairment

79
Q

What is goodpastures syndrome?

A

Antibodies to type IV collagen in glomerular BM develop, causing inflammation. Results in rapidly progressive glomerulonephritis, acute renal failure and lung hemorrhage.

80
Q

How is goodpastures syndrome treated?

A

Plasma exchange to remove antibodies

Corticosteroids to reduce inflammation