Case 2 Flashcards
(248 cards)
1
Q
What is the peritoneum?
A
Flattened mesothelial cells, with an immune function, over a connective base. This lines the abdominal cavity.
2
Q
What two structures is the peritoneal cavity between?
A
The Parietal and Visceral peritoneum.
3
Q
An alternative name for peritoneal cavity is…
*What fluid is here?
A
Potential Space
*Serous Fluid
4
Q
Give two compartments of the peritoneal cavity
A
The Greater Sac and the Lesser Sac
5
Q
Describe where the Greater Sac is
A
Superiorly - behind liver
Inferiorly - between layers of Great Omentum
Infront of Transverse Mesocolon
6
Q
Describe where the Lesser Sac is
A
The space behind the stomach (structures can travel here)
7
Q
How are the Greater and Lesser Sac connected?
A
Through the Epiploic Foramen (can put finger in here)
8
Q
What is the outside layer of Peritoneum called?
A
Parietal Peritoneum
9
Q
When the Parietal Peritoneum dips inwards, folds ( = two layers) and covers an organ, it becomes…
A
Visceral Peritoneum
10
Q
What is the Greater Omentum?
A
4 layers of Visceral Peritoneum
11
Q
Give the 9 quadrant model of the abdominal cavity
A
Right Hypochondriac, Epigastric, Left Hypochondriac
Right Lumbar (flank), Umbilical, Left Lumbar (flank)
Right Iliac Fossa, Hypogastric, Left Iliac Fossa
12
Q
Give the 4 quadrant model of the abdominal cavity
A
Right Upper Quadrant (UQ), Left UQ
Right Lower Quadrant (LQ), Left LQ
13
Q
What is the Lesser Omentum?
A
2 layers of Visceral Peritoneum
14
Q
Describe the location of the Greater Omentum
A
Starts from greater curvature of stomach, descends, covers small intestine (like an apron), folds back, and attaches to anterior surface of transverse colon.
15
Q
Describe the location of the Lesser Omentum
A
Starts from liver and joins the lesser curvature of stomach and proximal duodenum.
16
Q
What is peritonitis?
A
When fluid builds up in the potential space, leading to infection.
17
Q
What is the abdominal cavity in-between?
A
Ribcage and pelvis
18
Q
Women have a greater risk of peritonitis. Why?
A
Peritoneal cavity is not closed because of uterine tubes, uterus and vagina. However, it is rare to develop this disease.
19
Q
Organs outside the/posterior to the peritoneum are called…
A
Retroperitoneal
20
Q
Organs inside the peritoneum are called…
A
Intraperitoneal
21
Q
What are Peritoneal reflections?
A
Folds in peritoneum which attach organs to the abdominal walls or organs to other organs.
22
Q
Name all the ligaments in the body
A
Stomach-Diaphragm = Gastrophrenic Stomach-Intestine = Gastrocolic Stomach-Spleen = Gastrosplenic This joins the greater curvature of stomach to spleen. Has short gastric vessels and left gastro-epiploic vessels. Spleen-Kidney = Splenorenal
Stomach = gastro Diaphragm = phrenic Intestine = colic Kidney = renal
23
Q
What are the peritoneum folds that attach organs to other organs?
A
Ligaments
24
Q
Describe the peritoneum fold that joins the Liver to the abdominal wall
A
Falciform
Triangular ligament - posterior layer of left lobe of liver to diaphragm
-anterior layer continuous with left layer of falciform
25
Describe the peritoneum fold that joins the small intestine to the abdominal wall
Mesentery of SI
| Two layers of visceral peritoneum wrap around SI and attach to wall.
26
What is the small bowel mesentery?
Broad, fan shaped fold of peritoneum connecting jejunum and ileum to posterior abdominal wall.
27
What is the Transverse Mesocolon?
Transverse colon of Left Intestine to wall
-Visceral layer from greater omentum
-Meets Transverse colon and splits
-Wraps around Transverse colon
-Reattaches on other side of Transverse colon
=TM
28
What does the Transverse Mesocolon separate the abdominal cavity into?
Supracolic and infracolic compartment
29
Why is it important that the greater momentum can migrate?
If the appendix bursts, the GO can migrate and wrap around it. This stops infection as appendix has faeces in it.
'Known as 'policemen of the abdomen'
30
Where is the supra colic compartment and what does it contain?
Lies above the transverse mesocolon, between the diaphragm and the transverse colon.
It contains three major organs: the stomach, the liver and the spleen
Has subphrenic recess - space inferior to diaphragm, which is divided into the left and right recesses by falciform.
Has hepatorenal recess (of Morisson) - space between liver and kidney, lowest in supine position.
31
Where is the infra colic compartment?
Below the transverse mesocolon and transverse colon.
32
Where are gutters found?
Supracolic and infracolic compartment
33
What are gutters?
Deep impressions in posterior abdominal region, allow communication between compartments
34
What is an important gutter and why?
Right lateral paracholic gutter
| No ligaments here, so infection can travel up.
35
Where are the paracolic gutters found?
Outside intestines
36
Where are the infracolic gutters found?
Within the intestines
37
What divides the gutters into left and right?
Mesentery of Small Intestine
38
What are three types of gutters?
Lateral
Medial
Infracolic
39
What are medial gutters limited by?
Transverse mesocolon
40
What is the left parabolic space limited by?
Phrenicolic ligament
41
How can infection spread in the peritoneal cavity?
- Fluid builds up in spaces
- Create space between reflections
- Spaces are continuous
- Infection spreads
42
What is Paracentesis?
Surgical drainage of cavity.
| A needle and cannula through the anterolateral abdominal wall to drain fluid.
43
What does extraperitoneal mean?
Position of abdomen and pelvis not within the peritoneum
44
What does sub peritoneal mean?
Lies inferior to peritoneum
45
Describe the development of the gut tube into the duodenum
-Gut tube starts off as simple tube
-Three parts; 1st part of tube/ foregut rotates and makes stomach, liver and 1st part of duodenum.
-midgut/middle part of gut tube makes jejunum, ileum, ascending colon and medial 2/3's of transverse colon.
-hindgut/last part of gut tube makes descending colon, sigmoid colon and rectum.
Mesogastrium is double layered peritoneum attaches foregut to anterior and posterior abdominal walls.
Back - dorsal mesogastrium (greater curve of stomach, spleen grows here)
Front - ventral mesogastrium (lesser curve of stomach, liver grows here)
46
What organs are within the intraperitoneal compartment?
stomach, spleen, liver, bulb of the duodenum, jejunum, ileum, transverse colon, and sigmoid colon
47
Describe the features of a kidney and what they do (not micro anatomical)
- Triangles on outer edge of kidney are Medullary pyramids
- Minor calyces: what Medullary pyramid branches off
- Renal papilla: in between medullary pyramid and minor calyx, urine drains into ureter here
- Major calyces: what Minor calyces branch off
- Renal cortex: outside, on top of Medullary pyramid
- Renal column: in between Medullary pyramids
- Renal artery: drain into Major calyces of renal sinus, joins to abdominal aorta, waste comes in here
- Renal vein: drains into Major calyces of renal sinus, connected to IVC back to heart
- Arcuate artery: boundary between medulla and cortex
- Ureter: drains out of renal pelvis into bladder
- Renal sinus: spaces between Major and Minor calyces.
48
What is the kidney's role?
To filter blood and remove waste.
49
Describe the branching of the renal artery into the kidney
Renal artery - interlober artery - interlobular artery
| Kidney is divided into lobes which become lobules
50
What does the glomerulus do?
Filters blood
51
What does the afferent arteriole do?
Takes blood to glomerulus
52
What does the efferent arteriole do?
Takes blood away from the glomerulus
53
Where are glomeruli found?
Cortex of kidney
54
Where are the loops of henle found?
Medulla of kidney
55
What are vasa recta?
Long, straight vessels which are looped and match up with loops of henle in medulla.
Have red blood cells
56
What does the arcuate vein do?
Above arcuate artery, joins to Renal Vein
57
Describe what happens to blood as it enters kidney
- Blood from heart in aorta
- Blood enters kidney through Renal Artery
- Interlobar arteries
- Arcuate arteries
- Interlobular arteries
- Afferent arteriole
- Blood supplied to nephron
- Blood filtered through glomerulus
- Efferent arteriole
- Peritubular plexus, associated with PCT (Proximal Convoluted Tubule) and DCT (Distal Convoluted Tubule)
- Blood into Vasa Recta as venous drainage
58
The nephron is a simple structure where urine is drained into. True/False?
False
| Urine does drain here, but nephron has many different parts, all with own roles.
59
Where does urine collect in the medullary?
Cortical collecting duct
60
What is the Bowman's Capsule?
Blind end of the nephron
61
What is the role of the Mesangium?
Support for the glomerulus
62
Describe the features of Mesangium
- Fenestrated endothelium: allows filtration into urinary space
- Basement membrane: secreted by endothelium and podocytes
- Podocyte: interlocking foot like processes
- Lamina rare interna: layer over basement membrane
- Lamina densa: in between rara externally and rare international
- Lamina rara externa: outermost layer
63
Describe the structure of the glomerulus
- Surrounded by Bowman's Capsule
- Made of capillaries
- Urinary space allows filtration
- Afferent and efferent arteriole connected to it
64
Where is the cortical labyrinth?
Adjacent to glomeruli
65
What structures are in the cortical labyrinth?
- Efferent arteriole
- Afferent arteriole
- Juxtaglomerular cells (secrete renin which controls BP)
- Mesangial cells
- Lacis cells (type of Mesangial cells, support and involved in phagocytosis)
- Proximal Convoluted Tubules (thick walls to control reabsorption)
66
What structures are in the medulla?
- Vasa Recta
- Collecting duct
- Loops of Henle
67
Describe the features of Loops of Henle
- Different sized walls
- All packed together
- Have supporting cells
- Simple
- Lumen surrounded by walls
68
Describe the lower urinary tract
Renal pelvis - Ureter - Bladder - Urethra
69
What types of muscle are there in the urinary tract?
- Submucosa
- Urothelium lining
- Right spiral muscle
- Loose muscle spiral
70
How does urine move from the ureter to the bladder?
-Muscular walls contract = Peristalsis
| = urine forced down ureter to bladder
71
Describe the structure of the lumen
- Stellate lumen (rings of muscle)
- Smooth muscle around stellate lumen
- Urothelium on outside
72
Describe the structure of the bladder
- 3 layers of smooth muscle
- Submucosal layer below epithelium (made of collagen)
- Urothelium layer which expands when bladder is full
73
Describe the structure of urothelium of bladder
- Bottom layer is cuboidal basal cells
- Intermediate layer is polygonal cells
- Top layer is 'umbrella', dome shaped, binucleate and protect from urine
- Distended flattened layer at top, full of urine. Urine is unable to get out
74
The urothelium of the bladder is in a fixed position. True/False?
False
| It changes structure in different states
75
What are the three phases of kidney development in the embryo?
- Pronephros
- Mesonephros
- Metanephros
76
What happens during pronephros?
- Kidney near head of embryo
| - Transient (non-functional) in humans
77
What happens during metanephros?
-Weeks 4-12 (transient)
-Limited functionality
Week 5: Intermediate mesoderm formed (will become nephrons)
Mesonephric duct formed
Ureteric bud off mesonephric duct
Week 6: Branching
Week 7: Metanephric mass formed
Major Calyx forms
Further branching
Week 8: Major and Minor Calyx fully formed
Lobules formed
Ureter formed
Renal Pelvis formed
78
What happens during mesonephros?
Definitive human kidney formed
| Functional by week 12
79
Describe the migration of a normal kidney
Kidneys move up posterior wall into suprarenal glands (look like hats)
Week 6: Hilum started facing anteriorly (front), as kidneys go up, kidneys rotate and hilum faces medially.
Week 7-9: Transient and renal arteries branch from aorta. Kidneys have fully grown into glands
80
What are the possible development defects in kidneys?
Renal agenesis: 1 or both kidneys fail to develop or migrate. If both, then it is fatal.
Unilateral renal hypoplasia: kidney not fully developed
Supernumerary kidney: extra kidney
81
What are the possible malignation defects in kidneys?
Renal Ectopia: kidney doesn't migrate and remains in pelvis
Abnormal Rotation: hilum is still ventral
Horseshoe kidney: both kidneys fuse at midline
Supernumary (multiple) renal vessels: transient renal vessels don't disappear, trapping ureter. Hydronephrosis can happen, this is when urine builds up.
82
What are the three fluid compartments within the body? (Give their percentage of fluid)
-Intracellular (in cells, 40% of Body Weight)
-Extracellular (outside cells) splits into
Interstitial (outside cells with plasma, 15% of BW) and Plasma (5% of BW)
83
What determines the size of a fluid compartment?
No. of osmotically active particles as water follows these.
84
What happens to the volume of a compartment if there is an increase in osmotically active particles.
Volume increases, because water will move along gradient from other compartments. (Vice versa if particles are lost).
85
Water can freely move across compartments. True/False?
True
86
The osmolality of each compartment is 140mOsm/kg. True/False?
False
| It is actually 280mOsm/kg
87
Which specific particles control the intracellular fluid compartment?
K+, HCO3-, Cl-
88
How does the intracellular compartment react to volume changes?
-Volume goes down
-Membrane can actively take up particles
= increase in fluid
-Na-K pump helps in this regulation
(Vice versa if fluid is gained - particles are removed from compartment)
89
Which particles specifically control the size of the Interstitial and Plasma?
Na+, HCO3- and Cl-
90
Like the intracellular compartment, the Extracellular compartments (Interstitial and Plasma) can also self regulate their volume. True/False?
False
Their volume is determined by Starling forces = proteins are unable the plasma space, so are trapped there.
Proteins are freely permeable across the vascular wall, so if they leave the plasma and enter the Interstitial then the normal state is disturbed.
91
What is Colloid Osmotic pressure?
No. of osmotically active particles and drives water back into capillaries
92
What is hydrostatic pressure?
Pushes fluid out of capillaries into interstitium
93
What happens if COP and HP are balanced?
No net gain or loss of fluid
94
What happens to Starling forces if protein is lost?
```
Decreased COP
Balance disrupted
HP is able to decrease more before COP can act
= Loss of fluid
Blood volume decreases
Interstitium increases in volume
```
95
Why is fluid balance important in blood?
-Control BP
Lose fluid = BP drops
Gain fluid = BP increases
-Enough blood for organ perfusion
96
Why is fluid balance important in the interstitium?
-Stop oedemas forming
97
Why is fluid balance important in cells?
-Protect cells from shrinking or swelling
Water in brain - increase in inter cranial pressure - blood vessels squeeze down on - irreversible cell death = brain pushes down on spinal cord = brainstem compressed = death
Shrinking tears blood vessels and neurones = coma/death
98
Why is fluid balance important in plasma?
Plasma volume decreases = BP increases = stroke
| Plasma volume increases = anoxia (absence of oxygen)
99
What does Starlings suggest?
Starlings hypothesis states that the fluid movement due to filtration across the wall of a capillary is dependent on the balance between the hydrostatic pressure gradient and the oncotic pressure gradient across the capillary.
100
Why is it important to take fluid in slowly?
Rapid changes in water balance can be fatal
101
How does the kidney help maintain fluid balance?
- Controls plasma volume through amount of Na+ in body
- Stretch receptors on vasculature that detect plasma volume as vascular 'stretch'
- Volume receptors detect plasma volume
- Osmoreceptors detect osmolality
102
What is isotonic/isosmotic dehydration?
Amount of Na lost is equal to water lost (H2O=NaCl)
103
How does isotonic/isosmotic dehydration happen?
Internal: ileus, ascites, pleural effusion (fluid lost to lungs)
External: vomiting, diarrhoea, haemorrhage, burns
Mechanism:
-Fluid lost from plasma
-Starlings forces drive fluid from interstitial compartment
= Decrease in ECF volume but no change in ECF osmolality
= no change in ICF volume on osmolality
104
How is isotonic/isosmotic dehydration treated?
Volume loss = isotonic NaCl solution
| Blood loss = whole blood or plasma expander
105
What is hyperosmotic dehydration?
When fluid lost from plasma has more NaCl than water
106
Describe what happens during hyposmotic dehydration
-Fluid lost from plasma
-Plasma volume decreases = hyposmotic when compared to interstitial
-Osmotic gradient pushes water to interstitial = volume increases but osmolality decreases = hyposmotic compared to intracellular fluid
-Osmotic gradient pushes water to intracellular fluid
-volume increases but osmolality decreases
Overall:
decreased Extracellular volume and osmolality
increased intracellular volume and decreased intracellular osmolality
107
What causes hyposmotic dehydration
- Renal loss of NaCl because of adrenal insufficiency (Addison's disease)
- Diuretics
- Vomiting
- Heavy loss of hyposmotic sweat
108
How is hyposmotic dehydration treated?
0.9% NaCl isotonic fluid replacement
109
What is hyperosmotic dehydration?
When the fluid lost is more H20 than NaCl
110
Describe what happens during hyperosmotic Dehydration?
-Fluid lost
-Plasma volume decreases and more hyperosmotic that interstitial
-Starlings Forces and osmotic gradient push water from interstitial compartment = Interstitial volume decreases but osmolality increases
-Decrease in Extracellular compartment volume and increase in osmolality
-Extracellular compartment is more hyperosmotic that Intracellular compartment
-Osmotic gradient pushes fluid from ICF
= ICF volume decreases but osmolality increases
Overall, ECF and ICF volume decreases
ECF and ICF osmolality increases
111
What causes hyperosmotic dehydration?
```
Fever
Diabetes insipidus (increase in urine and thirst)
Diabetes mellitus
Excess loss of skin/breath
Decreased intake of water
Decreased ADH secretion
Stroke
Diarrhoea
```
112
How is hyperosmotic dehydration treated?
Slow water replacement (water that has 10% dextrose)
113
Why is it dangerous if children lose a lot of fluid?
Their fluid proportions are different, so losing a lot of fluid can be fatal - so they should always be treated first.
114
Kidneys get the most blood in the body as they have to filter it. Describe how this blood is distributed in the kidneys.
93% of blood goes to the Cortex
7% goes to Medulla
1% goes to Papilla
115
What types of nephrons are there?
- Superficial
- Mid-cortical
- Juxtamedullary
116
What are superficial nephrons?
- Close to surface
- All in cortex
- Proximal tubule in cortex
- Short loop of Henle
117
What are mid-cortical nephrons?
- Glomerulus in middle of cortex
- Loop of Henle descends into medulla
- Mainly in cortex (blood supply)
118
What a juxtamedullary nephrons?
- Brings blood to medulla
- Glomerulus close to cortical border (between cortex and medulla)
- Long loops of Henle
- Blood from Renal Artery
119
Why does only 7% of blood go to the Medulla?
Urine is produced here
120
Describe the process of blood flow in the superficial and mid-cortical nephrons
- Renal blood in left and right Renal artery
- Artery branches into segmental, interlobar, arcuate and interlobular arteries
- 1 arteriole to 1 nephron
- Covers glomerulus as network of capillaries
- Join together to form efferent arteriole
- Divide to form peritubular capillaries surrounding nephrons
- Peritubular venue, interlobar vein and renal vein leave
121
Describe the process of blood flow in the juxtamedullary nephrons
- Afferent arteriole formed
- Goes to medulla as vasa recta vessels
- Divide to become peritubular capillaries
- Surround medullary segments of nephrons
- Peritubular venue, interlobar and renal vein leave kidney
122
How much CO goes to the kidney?
25%
123
What is happening in the cortex of the kidney?
- Proximal tubules here are the main site of reabsorption of solutes and water
- Waste products and drugs are added to the filtrate
- A high blood supply is needed
124
What is happening in the medulla of the kidney?
- Urine is made here
- Medulla generates a hyperosmotic interstitial
- Low blood flow means it's not washed out
- The medullary blood supply is in a loop, a there can be an exchange of solutes
125
What is the importance of vascular resistance?
It maintains filtration pressure across the length of the capillary bed
This maintains renal blood flow and GFR
126
Where are the sites of vascular resistance in the kidneys?
Afferent and efferent arterioles
127
Hydrostatic pressure drops as you go along the glomerulus and systemic capillaries. True/False?
False
| HP drops in systemic capillaries, but remains constant in glomerulus (this drives filtration)
128
How do Afferent arterioles control vascular resistance?
- Constrict = Increase resistance = Decrease renal blood flow, filtration pressure (FP) and GFR
- Dilate = Decrease resistance = Increase RBF, FP and GFR
129
How do Efferent arterioles control vascular resistance?
- Constrict = decrease in RBF, increase I. FP and GFR
| - Dilate = increase in RBF, decrease in FP and GFR
130
How is Renal Blood Flow measured?
Clearance of PAH
| In a clinical setting, measure using contrast enhanced ultrasound
131
Is renal blood flow affected by systemic pressure?
No
If Systemic pressure increases, then BP will increase and blood flow in systemic circulation will increase
However, RBF stays the same
RBF is independent of systemic pressure
132
Describe the structure of the glomerular apparatus that helps it filter
Distal tubule is folded back on itself
| So when blood flow increases, more water and small molecules filter out.
133
What range of mercury does the kidney auto regulate in?
80-180 mml
134
What would happen if the kidney couldn't auto regulate?
Would depend on systemic BP and blood flow
135
What is the Myogenic Reflex?
```
Used to regulate renal BP e.g.
-Systemic BP increases
-Renal Blood flow increases
-Afferent arteriole stretches (Ca channels open up = influx of Ca+)
-Smooth muscle contraction
-Increase in resistance
-Renal blood flow back to normal
=GFR stabilised
```
136
What is the Tubular Glomerular feedback?
- Systemic BP increases
- Increase in renal blood flow
- Increase in filtration pressure
- Increased amount of fluid and molecules filtered per unit of time
- more NaCl filtered (sensed by Macula Densa cells in juxtaglomerular nephrons)
- NaCl transported to distal tube (more NaCl = more transport)
137
What is adenosine?
Neurotransmitter involved in controlling RBF and GFR
138
How does Adenosine work?
-Adenosine released form Macula Densa cells
-Diffuses to adjacent afferent arteriole
-Acts on A1 receptors
-Ca enters
-Smooth muscle contraction
= afferent arteriole increases
= RBF and GFR stabilised
139
What protective mechanism is put in place when a haemorrhage (bleeding) occurs?
Blood loss = Systemic blood volume and BP goes down = Perfusion of organs decreased
Blood needs to be diverted from the kidneys:
- Decrease in BP stimulates renal sympathetic nerves to release NEP and adrenal gland to release EP
- Angiotension II generated from rise in plasma renin concentration = constriction of renal arteries
140
What is the effect of a high concentration of a vasoconstrictor on afferent arterioles?
- Decrease of renal blood flow
- Decrease in GFR = Blood stays in systemic circulation
* if this happens for too long, then the kidney will die
141
What is the effect of a low concentration of a vasoconstrictor on efferent arterioles?
- Decrease in diameter
- Increase in resistance
- Decrease in RBF
- GFR drops slightly
142
What hormone is released when the kidney is about to die and how does it work?
Decrease in RBF and O2 stimulates medulla to release Prostoglandin
This is a vasodilator - increases RBF, allows perfusion of kidney and stops kidney from dying.
143
What inhibits Prostoglandin?
NSAIDS
| Dangerous to give to women (already have low BP)
144
What stimulates normal NO production?
- Stress (force on blood vessel)
- Histamine (inflammatory)
- Brakykinin ( inflammatory)
- ATP
145
What does NO do?
Causes Vasodilation and Renal Peripheration
146
What is the danger of abnormal production of NO in Diabetes Mellitus and Hypertension?
Too much dilation = damage to blood vessels/vascular damage
147
Where is the retovesical pouch in males?
Between bladder and rectum
148
Where is the vesicouterine pouch in females?
Between bladder and uterus
149
Describe how renal hypertension can happen from a false signal?
-Renal artery is narrowed
-Decrease in RBF
-Increase in Angiotensin II
=Peripheral resistance and aldosterone induced Na reabsorption (=increase in blood volume)
=Hypertension
150
What is the volume of distribution?
The concentration of the drug in the plasma
| concentration of drug when initially taken
151
What affects the volume of distribution?
- How permeable the drug is across the membrane
- Whether it binds to compartments (like proteins)
- pH partition (bases accumulate in acidic compartments)
152
If a drug has a very high volume of distribution, what does that suggest?
It is lipid soluble and has been stored in fatty/adipose tissue.
153
How is the volume of distribution calculated?
Dose (D)/ drug plasma concentration (Co)
154
How can the initial drug plasma concentration be found from a graph?
-Point the plots of the curve
-Extrapolate to when time = 0
= initial plasma concentration of blood
155
What is clearance?
- Not excretion
| - Clearing of drug from plasma per unit of time (e.g. per second)
156
What affects clearance (Cl)?
Metabolism
157
What is a half life (t1/2)?
Time then for the concentration of a drug to half
158
What affects the half life of a drug?
Faster metabolism = short half life = not in plasma long
159
What is used to work out the dosage of a drug?
The half life
160
How is the half life of a drug calculated?
Using graph:
-Choose a point on the concentration side
-See how long it takes for that concentration to half
OR
Use t1/2 = 0.693/Kel (elimination rate constant)
161
How is clearance calculated?
Kel x Volume of Distribution
| Kel = 0.693/ t1/2
162
Draw and describe a graph for a drug that has 1st order kinetics
- Descending curve, touches line
- Concentration on side, time at bottom
- 'At first, the drug is cleared from the plasma at a rate proportional to the plasma level. However, as more drug is given, more drug is cleared out. This is an example of a prescribed drug.
163
Draw and describe a graph for a drug that has 0 order kinetics
- Straight line descending
- Plasma concentration on side, time at bottom
- Drug is cleared at a constant rate (independent of plasma)
- Drugs cleared through enzymes, once these are saturated, this gives a constant rate of clearance
164
What is a steady state (Css)?
The point where the amount of drug given exactly replaces the amount lost
165
What is the therapeutic range?
The concentration of drug at which the patient will experience the desired clinical effect with a minimum of undesirable or adverse reactions.
166
What affects the therapeutic range?
Size of range: determined by the toxicity of the drug.
167
How can the drug plasma concentration be kept within the therapeutic range?
-Give small, frequent doses ( too much = toxic, too little = doesn't reach range)
168
How is steady state calculated?
Bioavailability x Dose / Interval dosing x Clearance
169
What is the loading dose?
Amount of drug initially given
170
How is the loading dose calculated?
Volume of distribution x desired steady state
| Vd x Css
171
What is the maintenance dose?
Frequent doses given after the initial dose to maintain the therapeutic range
Used to replace the drug lost through metabolism and excretion
172
Describe how a steady state is reached through repetitive dosing
1st does - 50% of steady state reached after 1st half life
2nd dose - 75% of Css (25% from 1st, 50% from 2nd)
3rd dose - 87.5% of Css (12.5% + 25% + 50%)
4th dose - 93.75% of Css
5th dose - 97% of Css
173
What is a 'short half' drug?
- Stays in body for a short amount of time
- Effects wear off quickly
- Need to take more of to prolong affects
174
What is a 'long half life' drug?
- Remains in body for longer
| - Take less of
175
How many doses is usually needed to reach a steady state?
5
176
How much of a drug should you give if the therapeutic range needs to be met quickly?
A high amount =
| An increased loading dose will hit the therapeutic range and the benefits of that drug will happen quickly
177
What are the features of the glomerulus?
Endothelial cell layer
Podocytes
Basement membrane
178
Describe the features of the endothelial cell layer and the functions of each feature
- Fenestrated endothelium (space between endothelial cell), looks like sieve
- permeable due to pores (fewer pores = less GFR)
- Movement of water and substances
- Barrier to large proteins
179
Describe the features of the basement membrane and the functions of each feature
- Made up of collagen fibril mesh
- Intertwined fibres
- Fusion of endothelial layer and podocytes
- Has collagen, laminin and proteoglycans
- Filters based on charge and size (this is lost in glomerular disease)
180
Describe the features of the Podocytes and the functions of each feature
- Filtration slits (from extensions crossing over) are 7 x 14nm
- Cover basement membrane facing Bowman's capsule
- Large cell body
- Extensions wrap around glomerulus capillaries
- Filtration slits make sure large molecules don't get through
181
COP changes in systemic circulation. True/False?
False
| Remains constant
182
What causes COP to be altered?
Hypertension and proteinuria
183
Describe the pressure changes in the systemic capillaries
1st half of capillary: HP > COP
2nd half of capillary : HP < COP
Overall, fluid exchange but no net movement
= no net filtration of fluid from blood into interstitium
184
Describe the pressure changes in glomerular capillaries (afferent and efferent)
*Small drop in pressure from afferent to efferent
Constant positive filtration pressure drives fluid and small molecules from blood across glomerular barrier into Bowman's capsule.
Called 'primary filtrate'
185
What happens if the HP = COP?
No/ negligable filtration
186
In the glomerular capillaries, it is always HP > COP. True/False?
True
| The constant net fluid movement means there is a gradual rise in COP along capillary.
187
How is GFR measured?
Measure a substance that is freely filtered at the glomerulus. Cannot be
- reabsorbed/secreted by nephron
- metabolised/produced by kidney
- alter GFR
188
Which substances are used to measure GFR?
Creatinine or Inulin
| The amount filtered = amount secreted
189
How is GFR calculated? (equation)
Urine Concentration (U) x Urine Flow / Plasma Concentration
OR
Uinulin x V (rate of urine concentration) = Pinulin (plasma concentration) x GFR
190
What is GFR?
Clearance of solute from blood that is freely filtered (not secreted/reabsorbed) per ml of blood per min
191
What is the value of Creatinine affected by?
Muscle bulk
| Hydration state
192
What is Creatinine the end product of?
Creatine Phosphate breaking down
193
If GFR drops by 1/2, what happens to the amount of Creatinine in the plasma?
x2
(GFR drops by 3/4, Creatinine x 4
GFR drops by 7/8, Creatinine x 8)
194
In steady state, the Creatinine plasma concentration is matched by its production/loss. True/False?
True
195
What affects GFR?
- Vascular Resistance
- Renal Blood Flow
- Changes in surface area (Kf)
- Changes in HP
- Changes in COP
196
How does vascular resistance affect GFR?
Afferent arterioles:
-Constrict = Decrease in RBF, FP and GFR
-Dilate = Increase in RBF, FP and GFR
Efferent arterioles:
-Constrict = Decrease in RBF, increase in FP and GFR
-Dilate = Increase in BRF, decrease in FP and GFR
197
How does renal blood flow affect GFR?
```
Vasoconstriction: (need ANP to dilate)
-High BP
-Blood vessels damaged
-Glomerulus damaged
-Scar tissue thickens barrier = decrease in GFR
Low BP:
-Hypoxic cell death (in medulla)
-Death of nephrons
-Decrease in functional glomeruli = decrease in GFR
```
198
How does changes in surface area of the glomerulus affect GFR?
Caused by disease (atherosclerosis, diabetic nephropathy, nephrotic syndrome, nephritic syndrome, infection)
Thickening of glomerular barrier (immune response to disease) = barrier becomes leaky to protein
= decrease in GFR
199
How does changes in HP affect GFR?
1. Increase pressure in capillaries = hypertension and volume tension = increase in GFR
2. Renal stones - kinks in ureter = blockage, fluid stuck in nephron = infection = decrease in GFR
200
How does changes in COP affect GFR?
Capillary:
Volume increases and protein decreases = decrease in COP across glomerulus = increase in GFR
Bowman's Capsule:
Protein decreases = increase in COP = increase in GFR
201
What is net HP?
Pressure in capillaries - Pressure in Bowman's space
202
What happens as proteinuria progresses?
- GFR decreases
- Decrease in circulation
- BP drops
- GFR auto regulation drops
- Afferent arteriole vasoconstriction
203
What is filtrate and where is it produced?
Initially, the concentration of the solute from glomerulus
204
What happens in the nephron?
Urine from filtrate comes here. Water and solute modified here.
205
Label a tubule
Glomerulus
| Nephron
206
Describe what happens to blood at the glomerulus
1. Left untouched, so the amount filtered = amount secreted. (Freely filtered)
2. Filtered, then reabsorbed. Amount secreted < amount filtered. (glucose, amino acids, Na+)
3. Filtered, then secreted. Amount secreted > amount filtered (drugs, metabolic end products).
All together = amount of urine
207
How much blood is filtered per day?
180L, 125ml/min of water
208
What is PAH and why is it important?
Para-amino-hippurate
| Tells us about the health of the kidney
209
What happens to glucose at low concentrations?
All reabsorbed in proximal tubule
| This is mediated bu transport proteins, SGLT2 (high capacity, low affinity) and SGLT1 (low capacity, low affinity)
210
Normally, the amount of inulin filtered is...
proportional to Pinulin x GFR
211
How do we use inulin to compare to the molecules?
Molecule in urine < inulin = reabsorbed
Molecule in urine > inulin = secreted
Molecule in urine = inulin is freely filtered
212
Glucose that is normally filtered is not lost in the urine. True/False?
True
213
What is the plasma threshold for glucose?
375mg/min
Initial amount of glucose in the urine is up to 12mM
This is 3x plasma glucose concentration, therefore the kidney does not control plasma glucose
214
Why might someone have excess glucose in their body?
Diabetes or familial glycosuria (defect in SGLT2)
215
How is phosphate handled in the kidney?
-10% of load/amount being filtered
-80% filtered in proximal tubule, 10% in distal tubule
-Transport proteins are NAPi2a and NAPi2c
-Tmax is0.1mM/min (if this is exceeded, then it will spill into the urine)
-Plasma threshold is 1.2mM in plasma phosphate (kidney does control plasma phosphate levels)
-PTH hormone can alter Tmax
Too much phosphate is dangerous
216
How is PAH handled in the kidney?
-Freely filtered and secreted
Rate = PPAH x GFR + secretion rate
-Filtered in glomerulus
-Efficiently secreted by proximal tubule (mediated by anionic transport proteins)
-Tmax is 80mMg/min
-Plasma threshold > plasma PAH
-No PAH left in renal blood (clearance of PAH = renal plasma flow)
217
Give the equation to calculate clearance of PAH
UPAH x V / PPAH
| Urine concentration of PAH X Volume / Plasma concentration of PAH
218
What is TMAX?
Time to Maximum Plasma Concentration/Maximum effect
219
What happens at the proximal tubule?
Solute is reabsorbed = used to create osmotic gradient for water reabsorption. 70% water is reabsorbed.
This is the same is hydrated and dehydrated states.
220
What happens at the Distal tubule connecting tubule?
Solute is reabsorbed = osmotic gradient drives water back into nephron
ADH controls the water reabsorption
4/5 % water is reabsorbed here
221
What happens in the loops of Henle?
```
Interaction of nephron segments
Hyperosmotic gradient around the tubule, so water is reabsorbed in the thin descending limb
No water reabsorbed in ascending limbs
20% of water reabsorbed
Independent of hydration state
```
222
How are water and osmolytes exchanged in the nephron?
Medulla - loops of Henle from mid cortical and juxtaglomerullary nephron have long loops and descend into medulla towards the papilla
There is countercurrent flow of filtrate in nephron (limbs going up and down)
This allows interaction between adjacent nephron segments = exchange of water and osmolytes
223
How is the hyperosmolar environment of the medulla made?
Blood to medulla is from juxtaglomerular efferent arterioles (this is 7 % of renal blood flow). Must stop osmotically active particles washing out to create hyperosmotic environment.
-Selective transport of water and salt in nephron segments
-Build up of NaCl and urea (40% of osmotically active particles in medulla)
= hyperosmolar environment of medulla
Overall, urea trapped in medulla = osmotic gradient
224
What is one concern in a low protein diet?
Reduction in urea in medulla = reduction in ability to make a concentrated urine
225
Describe the 'single effect'
-Filtrate enters the thin descending limb
-This filtrate is the same as plasma (300mOsM) = isosmotic
-Water is lost here
Filtrate enters ascending thin limb
-NaCl lost in ascending limb = 100mOsmM (hyposmotic compared to plasma)
226
What does ADH do to the collecting duct?
The collecting is impermeable to water unless ADH is present. ADH inserts water pores in the CD
227
What happens in the thin descending limb?
- NaCl and urea can't leave/enter
- Passes hyperosmotic interstitium = gradient across the tubule allows water to leave
- 20% of water left = 300mOsmM to 1200mOsM
228
What happens in the thin ascending limb?
-Water can't leave
-Gradient between tubular fluid and interstitium (from trapped urea)
-NaCl leaves tubule lumen
-Increased NaCl in interstitium
=osmolality of interstitium increases
-Decrease in osmolality of tubular lumen
-water driven out of descending tube
-Passive NaCl reabsorption down gradient
229
What happens in the thick ascending limb?
-Water can't leave
-NaCl and urea leave through Na:K:2Cl co transporter on apical side of tubular cell
-Urea can be absorbed
-NaCl increases in interstitium
= increase in osmolality of interstitium and decrease in O of tubular lumen
-Fluid is 100mOsM
-No ADH = dilute urine
-Active NaCl reabsorption from interstitium
230
Why is urea recycled?
To maintain the osmotic medulla
231
What is urea?
Product of protein metabolism
| A small molecule that is freely filtered in the nephron and cleared by the kidney
232
Describe what happens to urea when it reaches the nephron
-Proximal tubule
-50% reabsorbed back into blood
-Goes to thin ascending limb
-50% filtered load added to filtrate
-Thick ascending limb
-30% reabsorbed
Collecting duct
-55% reabsorbed
=15% in urine
233
What happens at the Collecting Duct?
This passes through the hyperosmotic interstitium of medulla.
If ADH is present = water is absorbed and a concentrated/high osmolality urine is produced.
If ADH is not present = no water reabsorbed and a dilute/low osmolality urine is produced.
This is dependent on state of hydration.
234
What makes up the loop of Henle?
Descending thin limb
| Thin and thick ascending limb
235
How is a dilute urine made?
-Fluid is in the descending thin limb
-the hypertonic interstitium removes water
=dilute and hypotonic urine
236
What happens at the vasa recta?
- Blood flows from afferent to vein
- Is permeable to water and solutes
- Osmotic gradient drives water from descending to ascending vessel
- Concentration gradient drives NaCl from ascending to descending vessel
- Water removed from medulla
237
What is diuresis?
Increased production of urine (dilute)
238
How does diuresis happen?
- No ADH
- No water absorbed in CD
- NaCl is absorbed
- Reduction in osmolality of tubular fluid
- Low osmolality urine
239
What is anti-diuresis?
Decreased production of urine (concentrated)
240
How does anti-diuresis happen?
-ADH from posterior pituitary
-Aquaporin water channels placed in CD
-Water and NaCl absorbed in CD
-Water absorption driven by osmotic gradient between tubular lumen and interstitium
=high osmolality urine
241
How is Na handled in the proximal tubule?
- Freely filtered in glomerulus (Rate = PNa x GFR)
- 70% of filtered Na is reabsorbed in proximal tubule
- Na/Cl co transport
- Na/solute co transport
- Passive NaCl absorption
- Na/HCO3 co transport
242
Describe the Na/solute co transport system
- Na gradient established (high ECF, low IF)
- Drives accumulation of solutes
- Uptake of solutes linked to uptake of Na across membrane of proximal tubule cells
* uses energy
* 10% of Na reabsorption
243
Which solutes and transporters are involved in the Na/solute co transport system?
```
Na/glucose uses SGLT1, SGLT2, SGLT3
Na/phosphate uses NaPi
Na/amino acid uses EAAC-1
Na/bile uses ASBT
Na/monacarboxylate uses MCT1
```
244
What is Fanconi Syndrome?
Damage to proximal tubule = solutes in urine
245
Describe how the solutes for the Na/HCO3 co transport system are collected
Need: H+, HCO3 and CO2
Na/H+ brings H+ into tubular lumen
HCO3 freely filtered at glomerulus (amount = PHCO3 x GFR)
CO2 freely permeable to renal proximal tubule's membrane
246
Describe what happens in the Na/HCO3 co transport system
1. HCO3 + H+ <> H2CO3 (Catalysed by carbonic anhydrase)
2.H2CO3 <> CO2 + H20
Reactions are reversed:
3. CO2 + H20 <> H2CO3
4. H2CO3 <> HCO3 + H+
HCO3 leaves the cell via Na/HCO3 transporter of basolateral membrane
Movement of Co2 and gain of Na from Na/H = Na and HCO3 from tubular lumen to proximal tubular lumen
Na leaves via Na K-ATPase at basolateral membrane
*40% of Na reabsorption
*Consumes energy
*in early proximal
247
Describe the Na/Cl co transport system
- Cl freely filtered by glomerulus
- Cl absorbed in exchange for organic anion (lactate, oxalate, formate) through Cl/OA transporter
- Cl leaves through second Cl/OA transporter
- This allows metabolic waste to be removed
- Uptake of Cl linked to uptake of Na
- OA accumulates in cell via TCA/OA exchanger at basolateral membrane
* 15% of Na reabsorption
* consumes energy
* in late proximal
248
Name everything in SADPUCKER
```
Suprarenal Glands
Aorta
Duodenum
Pancreas
Ureters
Colon
Kidneys
Eosophagus
Rectum
```
