Week 6 Flashcards
1
Q
What makes up the urine produced by the kidneys?
A
Removal, from circulating blood, of excess water & electrolytes, & tonic, metabolic waste products such as urea & creatinine
2
Q
How do the kidneys monitor and effect acid/base balance?
A
Excreting H+ during acidosis, or bicarbonate ions during alkalosis
3
Q
What does the secretion of renin by the kidneys do?
A
Indirectly raises blood pressure
4
Q
How often is blood filtered and “cleaned”?
A
Upto 60x per day
5
Q
What secretes erythropoietin?
A
Kidneys
6
Q
What is the fat surrounding the kidneys called?
A
Pararenal/nephric fat
7
Q
What overlies the hilum of the right kidney?
A
2nd part of the duodenum
8
Q
Why do the kidneys move with respiration?
A
Because they are related to the diaphragm
9
Q
What are the 5 parts to a kidney nephron?
A
- Renal corpuscle (glomerulus)
- Proximal convoluted tubule
- Loop of Henle
- Distal convoluted tubule
- Collecting ducts
10
Q
Describe the 2 functions of a nephron?
A
- Ultrafiltration- 180litres filtrate/24hr
2. Reabsorption- 1.5litres urine/24hr
11
Q
Where are the nephrons located in the kidney?
A
Renal pyramids
12
Q
What forms the renal pelvis?
A
Minor calyces converge on major calyces, which themselves form the renal pelvis that tucks into the sinus of the kidney
13
Q
What is the blood supply of the kidneys?
A
- Renal arteries from aorta at L1,2
- Accessory, extrahilar arteries from aorta
- Gonadal
- Common & internal iliac
- Uterine, vaginal
- Vesicle
14
Q
What are the vascular structures entering the renal hilum from anterior to posterior?
A
Vein –> Artery –> Pelvis of Ureter
15
Q
What does the left renal vein receive?
A
Suprarenal & gonadal veins
16
Q
Why is surgery difficult in the right kidney?
A
IVC is to the right of the midline, so the right renal vein is short
17
Q
How many segmental arteries does the renal artery divide into?
A
5
18
Q
What does the segmental artery give off?
A
Lobar arteries, one for each renal pyramid
19
Q
What does the lobar arteries give off before entering the renal substance?
A
2 or 3 interlobar arteries, which run toward the cortex on each side of the renal pyramid
20
Q
What do the interloper arteries give off at the junction of the cortex and the medulla?
A
Arcuate arteries, which arch over the bases of the pyramids
21
Q
What do the arcuate arteries give off?
A
Several interlobular arteries that ascend in the cortex
22
Q
What do the afferent glomerular arterioles arise from and what do they supply?
A
- Arise as branches of the interlobular arteries
- Supply renal corpuscle
23
Q
What is the nerve supply of the kidney?
A
T12 & L1
24
Q
Where does the referred pain of the kidneys go to?
A
Back & lumbar region, as well as loin to groin
25
What do afferents in the vagus cause?
Nausea & vomiting associated with pain
26
Describe the ureter?
- Muscular tube that transports urine to bladder
| - Retroperitoneal
27
Where are the 3 narrowings in the ureter?
1. Pelvi-ureteric junction
2. Crossing the pelvic brim
3. Passing through the bladder wall
28
What do the ureters cross?
Bifurcation of the common iliac artery
29
What should the ureters overlie according to anatomy books?
Lumbar transverse processes
30
What does IVU stand for?
Intravenous urogram
31
What 2 structures does the ureter lie between in the male pelvis?
Vas deferens & seminal vesicle
32
Describe the relationship between the ureter and structures in the female pelvis?
Posterior to ovary, inferior to uterine artery, passing cervix & lateral fornix of vagina
33
What lies in the lateral wall of the ureter (medial) in the pelvis?
- Internal iliac vessels & branches
- Lumbosacral trunk
- SI joint, ischial spine
34
What vascular supply should you perseveres during surgery?
Renal & Inferior vesicle branches
35
What is the lymph drainage of the ureter?
Para-aortic & iliac nodes
36
Describe how the ureters pass through the bladder wall?
Obliquely, creating flap valve that prevents urine backflow
37
What forces the ureters closed?
Pressure of urine in the full bladder
38
How would you describe pain of ureteric calculi?
Colicy due to peristaltic waves
39
What aids bladder emptying?
Raised intra-abdominal pressure
40
What is the epithelial lining of the ureter/bladder?
Transitional/Urothelium which is urine-proof & allows distension
41
Describe the different muscles of the ureter & their purpose?
- Smooth & involuntary, controlled by autonomic, particularly parasympathetic
- External sphincter is striated & voluntary
42
What is the nerve supple of the ureter?
- "Pacemakers" in renal calyces
| - Segmentally T10, 11, 12, L1, S2, 3, 4 from aortic, renal & pelvic plexuses
43
Where does referred pain of the ureter go?
T11 & L2, loin to groin & scrotum/labia
44
What is the bladders detrusor muscle nerve supply?
Parasympathetic S2, 3, 4
45
What is the bladder neck/urethral opening like in the male?
Preprostatic, internal sphincter (sympathetic) to prevent semen back flowing into the bladder
46
What is the bladder neck/urethral opening like in the female?
Bladder neck above the pelvic floor, pressure of pelvic organs & levator ani contribute to urinary continence
47
What happens to the peritoneum as the bladder distends?
It pushes upwards, above & behind so that the bladder then lies directly behind the anterior abdominal wall
48
Describe the urethra of the female?
- External sphincter of striated muscle inferior to bladder neck
- Embedded in anterior vaginal wall
- Opens in vulva as an antero-posterior slit immediately anterior to vagina
49
List the 4 parts of the male urethra?
1. Preprostatic at bladder neck (position of smooth internal sphincter)
2. Prostatic
3. Membranous, surrounded by striated external sphincter
4. Spongy/Penile Urethra
50
What is the arterial supply of the bladder & urethra?
Branches of internal iliac- sup & inf vesicle, internal pudendal
51
What is the venous supply of the bladder & urethra?
Vesical (& prostatic) plexuses converging on internal pudendal & internal iliac veins
52
What is the lymph supply of the bladder & urethra?
Internal & external iliac nodes
53
What communication in the urethra can facilitate tumour spread?
Prostate & valveless veins of vertebral plexuses (Batson)
54
What is the nerve supply of the bladder & urethra?
- Somatic motor for striated muscle
- Autonomic (sympathetic & parasympathetic)
- Sensatiosn from S2, 3, 4, Pudendal nerve, Sympathetic & parasympathetic Pelvic Plexus
55
Describe the 3 stages of Micturition/Urination?
1. STORAGE: parasympathetic to detrusor "switched off" bladder to relax & fill
2. "FULL", CAUSES DESIRE TO MICTURATE: afferents (sensory) to spinal cord, the "M" centre in pons stimulates preganglionic parasympathetic neurones at S2,3,4
3. VOID: 1y neurones stimulate 2y neurones in bladder wall ganglia, causing detrusor contraction. Simultaneous relaxation of external urethral sphincter via pudendal nerve & contraction of abdominal wall
56
What is the usual volume of urine in a male bladder?
| What volume causes pain?
- 400ml norm
| - 500ml pain in lower abdomen & perineum
57
How is Substance Use disorder classified by the DSM-V?
According to type of substance ie. alcohol, opiates, stimulants & sedatives
58
Describe & give examples of depressant substances?
Drugs that dampen down the CNS (alcohol, opioids, benzodiazepines)
59
Describe & give examples of stimulant substances?
Have excitatory effects on CNS (cocaine, amphetamine, nicotine, caffeine, ecstasy)
60
Give examples of hallucinogen substances?
- Cannabis
- LSD
- Mushrooms
- Solvents
61
What are the acute signs of alcohol use?
- Smell
- Slurred speech
- Flushing skin
- Disinhibition
- Tremor
- Agitation
- Mints/perfume
62
What are the acute signs of cannabis use?
- Bloodshot eyes
- Brown fingers
- Drowsiness/slowed down
- Smell
- Lack of focus/concentration
63
What are the acute signs of stimulant use?
- Agitation
- Pressure of speech
- Lack of focus/concentration
- Mood fluctuation
64
What are the acute signs of opiate use?
- Gauching
- "Pinned" pupils
- Signs of injecting
- Brown fingers
- Flu like symptoms (withdrawal)
65
What are the acute signs of sedatives?
- Drowsiness
- Slurred speech
- Poor memory/recollection
66
What are the 3 key policies in Scotland for substance use?
1. The Road to Recovery
2. Hidden Harm
3. Changing Scotland's Relationship with Alcohol
67
What 3 substances have a high >20% addiction potential?
- Heroin
- Methadone
- Nicotine
68
What 6 substances have a moderate 10-20% addiction potential?
- Amphetamines
- Ecstasy
- Cocaine
- Alcohol
- Cannabis
- Benzodiazepines
69
What 2 substances have a low 5-10% addiction potential?
- Inhalants
| - Steroids
70
What are the 6 different models of addiction?
1. Moral models
2. Disease models
3. Biological/Medical models
4. Personality models
5. Behavioural models
6. Biopsychosocial models
71
Describe Moral Models?
- Addiction seen as wilful violations of societal rules & norms, human weakness
- Individual is primary causal factor
- Treatment: moral persuasion, imprisonment or spiritual guidance
- Church, law enforcement & courts are "agents of change"
72
Describe Dispositional Disease Models?
- Primary causal factor is individual
- "Disease" of addiction is irreversible but can be arrested via total abstinence
- Benevolent model for individual & corporate organisations
- AA & NA subscribe in part to this model
73
Describe Biological/Medical Models?
- Genetic & physiological processes in determining addiction, primary causal factor is individual
- Identify unique biological conditions which contribute to addiction ie. disorder of brain function
- Consider pharmacology of substance
- Agent of change is medical
74
What is the evidence supporting Medical Model?
- Addiction is about 50% heritable (Sellman, 2010)
- Physiological processes influence vulnerability & behaviour
- Discrete neural circuits involved in different stages of addiction
75
What are the problems with the medical model?
- Medical treatment effectively reduce harm but are less effective in promoting abstinence
- Treatments do not exist for many addictive behaviours
76
Describe Personality Models?
- Primary causal factor is individual as addiction due to abnormal personality
- Poor impulse control, low self-esteem, inability to cope with stress, egocentricity, manipulative traits, need for control & power
- Resolution requires restructuring of personality, agent of change is psychiatry
77
Describe Behavioural Models?
- Conditioning is the process of behaviour modification whereby an individual comes to associate a desired behaviour with a previous unrelated stimuli
- Substance misuse is a learned behaviour, treatment is "relearning new behaviours"
78
What is the Classical (Pavlovian) Conditioning/ Associated Learning?
Learning by connecting 2 cues, one already elicits a response, the other comes too
79
What is the Operant (Skinnerian) Conditioning/ Instrumental Learning?
Learning by connecting the consequences of actions with preceding behaviours
80
Describe the Cognitive Behavioural Model?
- Changes in addictive behaviour occur due to changes in motivation, cognition & appraisal
- Assumption: changing content of cognition & motivation can influence behaviour
81
Describe controlled/explicit cognitive processing?
- Slow
- Deliberate
- Effortful
- Conscious
- Sequential
82
Describe automatic/implicit cognitive processing?
- Fast
- Unintentional
- No effort required
- Usually out of awareness
- In parallel
83
What 2 cognitive processes does addiction influence?
1. Attention bias
| 2. Memory bias
84
What are the 5 different thinking errors and give examples?
1. "Just a treat" - permission giving
2. "Only one" - minimisation
3. "Haven't used for a whole week, so why not?" - rationalisation
4. "I can use & stay in control" - denial
5. "She made me angry so I had to use it" - blaming
85
Describe the Biopsychosocial Model?
- Concerned with interaction of biological, psycholocial & social factors
- Holistic approach, no factors are dominant
86
What is Psychological formulation?
Understanding the development & function of substance use for an individual in the context of biopsychosocial model
87
What is the 3 step methods of assessment?
1. Self-report
2. Corroboration from other sources
3. Objective assessment methods
88
Describe the 1. Self-report step in assessment?
- Structured clinical interview
| - Standard assessment measures (drug, alcohol, cognitive assessment, mental health)
89
Describe the 3. Objective assessment methods in assessment?
- Drug use: analysis of urine, blood, saliva
- Injecting behaviour: examination of injecting sites
- Dependancy/withdrawal: observation while in withdrawal
- Blood born viruses: blood tests
- General health: full medical history
90
What are the 6 psychological stages of change (Prochaska & DiClemente)?
- Pre-contemplation
- Contemplation
- Preparation
- Action
- Maintenance
- Relapse
91
How do kidneys control water excretion?
Changing concentration of ions in the nephron tubule
92
What is the normal osmolarity of the extracellular fluid when entering the kidney?
300 mOsm/L
93
What is the osmolarity of extracellular fluid reduced to when it enters the distal convoluted tubule (DCT)?
~ 100 mOsm/L
94
Why is osmolarilty further reduced in the DCT & collecting ducts?
Reabsorption of sodium chloride
95
What happens to the DCT & collecting ducts in absence of ADH?
Impermeable to water & tubule fluid becomes more dilute (50 mOsm/L)
96
What does the failure to reabsorb water & continued reabsorption of ions lead to?
Large volume of dilute urine
97
What is type of urine is essential for survival?
More concentrated than plasma allowing conservation of water
98
What is the maximum urine a kidney can make?
1200-1400 mOsm/L which is 3-4x that of plasma
99
What allows the distal tubules & collecting ducts to become permeable to water?
High level of ADH
100
What are the 4 factors that contribute to the build up of osmolarity in the medulla?
1. Passive absorption of ions in thin ascending limb of Loop of Henle
2. Active transport of sodium ions & co-transport of potassium, chloride & other ions out of thick ascending limb of loop of Henle
3. Active transport of ions from collecting duct
4. Facilitate diffusion of urea from medullary portion of collection ducts into medullary interstitium
101
What sets up an osmotic imbalance & gradient?
Diffusion of small amounts of water from the medullary tubules into medullary interstitium, far less than reabsorption of ions that occurs there
102
Describe the different ion transport that can occur in the thin descending limb?
- Impermeable to salt
| - Water moves passively
103
Why does interstitial salt concentration increase as it moves towards hairpin bend?
Both passively & actively moved out of the ascending tubule
104
Describe the different ion transport that can occur in the thin ascending limb?
- Passive Na+ out of the tubule
| - No H2O movement
105
Describe the different ion transport that can occur in the thick ascending limb?
- Active pumping against Na+ gradient
| - No H2O movement
106
Describe the different ion transport that can occur in the collecting tubule?
H2O can move only if ADH present
107
What actively generates a concentration gradient being greater the deeper into the medulla?
The loop of Henle tubular counter-current mechanism
108
What is Step 1 of The loop of Henle tubular counter-current mechanism?
Fluid enters the loop of Henle from the PCT at 300 mOsm/L, the same as plasma
109
What is Step 2 of The loop of Henle tubular counter-current mechanism?
- Active transport of ions from the thick ascending limb establishes a 200 mOsm/L gradient between tubular fluid & interstitial fluid
- 400 mOsm/L in medullary interstitium, 200 mOsm/L in ascending tubule fluid
110
What is Step 3 of The loop of Henle tubular counter-current mechanism?
- Tubular fluid in descending limb now equilibrates with the interstitial fluid as water moves out of the descending limb into medullary interstitial fluid
- Continued transport of ions but not water in the ascending limb maintains the gradient
111
What is Step 4 of The loop of Henle tubular counter-current mechanism?
- Flow of fluid into the loop of Henle from PCT moves the fluid in the limbs on
- The hyperosmotic fluid in descending limb moves on into ascending limb.
112
What is Step 5 of The loop of Henle tubular counter-current mechanism?
- Additional ions are pumped out of the fluid from the ascending limb until a 200 mOsm/L gradient is established between ascending limb tubule fluid & medullary interstitium.
- This time the intersitial osmolarity rises to 500 mOsm/L & the ascending tubule falls to 300 mOsm/L.
113
What is Step 6 of The loop of Henle tubular counter-current mechanism?
- There is again movement of water out of descending limb of the loop of Henle to reach osmotic equilibrium with the medullary interstitial fluid
- This increases osmolarity of the tubule fluid in the descending limb up to 500 mOsm/L which moves on into the ascending limb for the processes of sodium & other ions movement to continue
114
What is osmolality?
Number of solute particles dissolved in 1 litre of water & reflects solution's ability to cause osmosis
115
How is concentrated urine formed?
- More water reabsorption into medullary interstitium
- High levels of ADH collecting ducts become permeable to water & fluid at end of collecting ducts is same osmolarity as renal medulla, about 1200 mOsm/L
116
Normally how much filtered urea is reabsorbed in the PCT?
40-50%
117
What can urea contribute to?
Osmolarity of medullary interstitial gradient when kidney needs to form maximally concentrated urine in dehydration
118
What causes an increase in urea concentration?
Water reabsorption (increase ADH)
119
Where does Urea move from-to when highly concentrated?
Medullary collecting ducts --> medullary interstitial fluid
120
Where in the tubule can a moderate amount of urea move back in?
Inner medullary section of the Loop of Henle & so can recirculate
121
What can Urea recirculation provide?
- Concentration of urea in distal tubular fluid in times of dehydration
- Additional mechanism for formation of hyper osmotic renal medulla
122
What % of total renal blood flow is medullary blood flow?
~5%
123
What does the vasa recta do?
Serves as a counter current mechanism to prevent the washout of solutes from the medullary interstitium
124
What happens to blood when it enters/exits the medullary interstitium?
More hypertonic as it descends into medullary interstitium, less hypertonic as it ascends back towards cortical regions
125
What is the negative feedback when the body senses a water deficit?
Increase extracellular osmolarity --> increase ADH secretion --> Increase plasma ADH --> increase H2O permeability in DT, CD --> Increase H2O reabsorption --> Decrease H2O excreted
126
Where is ADH secreted from?
Posterior pituitary
127
What drugs can cause increase in ADH?
- Morphine
- Nicotine
- Cyclophosphamide
128
What 5 factors causes an increase in ADH?
- Increase plasma osmolarity
- Decrease blood volume
- Decrease blood pressure
- Nausea
- Hypoxia
129
What drugs can cause decrease in ADH?
- Alcohol
- Clonidine (antihypertensive)
- Haloperidol (dopamine blocker)
130
What 3 factors causes a decrease in ADH?
- Decrease plasma osmolarity
- Increase blood volume
- Increase blood pressure
131
What is the difference between glomerular filtration & tubular reabsorption?
Tubular reabsorption is highly selective
132
Describe active transport in the kidney tubular cells?
Sodium-potassium pump transports Na+ from interior of cell across basolateral membrane creating low intracellular Na+ concentration & negative intracellular electrical potential
133
What is active transport?
Move solute against electrochemical gradient & requires energy from ATP
134
What is secondary active transport?
1 substance diffuses down its electrochemical gradient (sodium), the energy released is used to drive another substance (glucose) against its electrochemical gradient, no ATP required
135
What is NHE?
Secondar active transport, Na+/H+ exchanger
136
What is SGLT?
Sodium glucose co-transporter
137
Describe the cellular ultrastructure & primary transport of Proximal tubule?
- 65% filtered sodium & water reabsorbed here
- High capacity for reabsorption with high metabolically active cells
- Sodium pump driven
- Co-transport
- Secretion
- Organic acids/bases
- Metabolic products
- Drugs & toxins
138
Describe the cellular ultrastructure & transport characteristics of the Loop of Henle?
- 20% filtered water & 25% filtered sodium, chloride & potassium reabsorbed
- Thin descending segment permeable to water-diffusion
- Thick ascending limb has active transporters & absorbs sodium chloride & potassium
139
Describe the cellular ultrastructure & transport characteristics of the early & late distal tubule?
- 5% filtered load of sodium absorbed
- Impermeable to water
- Pumps/absorbs sodium, chloride & potassium
- Urine more dilute
- Principle cells absorb H2O & Na+
- Intercalated cells absorb K+ & secrete H+
140
Describe the cellular ultrastructure & transport characteristics of the medullary collecting ducts?
- Absorbs <10% filtered water & sodium ions
- Vital to produce dilute/concentrated urine
- Impermeable to water unless ADH present
- Permeable to urea & has urea transporters
- Secrete H+ so plays role in acid/base balance
141
What is the final site for processing urine?
Medullary collecting ducts
142
What is the site of action of aldosterone hormone?
Collecting tubule & duct
143
What are the effects of aldosterone hormone?
- Increase NaCl & H2O reabsorption
| - Increase K+ secretion
144
What are the sites of action of angiotensin II hormone?
- Proximal tubule
- Thick ascending loop of Henle
- Distal tubule
- Collecting tubule
145
What are the effects of angiotensin II hormone?
- Increase NaCl & H2O reabsorption
| - Increase H+ secretion
146
What are the sites of action of antidiuretic hormone?
- Distal tubule
| - Collecting tubule/duct
147
What is the effect of antidiuretic hormone?
Increase H2O reabsorption
148
What are the sites of action of atrial natriuretic peptide hormone?
- Distal tubule
| - Collecting tubule/duct
149
What is the effect of atrial natriuretic peptide hormone?
Decrease NaCl reabsorption
150
What are the sites of action of parathyroid hormone?
- Proximal tubule
- Thick ascending loop of Henle
- Distal tubule
151
What are the effects of parathyroid hormone?
- Decrease PO4 reabsorption
| - Increase Ca2+ reabsorption
152
Where is aldosterone hormone released?
Adrenal cortex
153
What does aldosterone stimulate?
Sodium-potassium ATPase pump on basolateral side of cortical collecting tubule membrane
154
When does angiotensin II hormone kick into action?
During haemorrhage, loss of salt & water
155
What can angiotensin II stimulate?
Aldosterone release
156
What effects does angiotensin II hormone have on kidney arterioles?
Constricts afferent &/or efferent arterioles
157
What does angiotensin II hormone specifically stimulate in tubular cells?
- Sodium pump on basolateral side of tubular epithelia
| - Sodium-hydrogen exchange on luminal membrane
158
What does ADH bind to?
| What does ADH do?
- Specific V2 receptors
- Through signal transduction mechanisms stimulate the movement of aquaporin 2 to the apical (luminal) surface of the epithelial cells (reversible)
159
What secrete atrial natriuretic hormone?
Cardiac atria when they are distended by increased blood volume
160
What regulatory effects does the sympathetic nervous system have on tubular reabsorption?
- Decrease Na+ and H2O excretion mainly by constricting renal arterioles & so GFR
- Increase angiotensin II
161
What can untreated hypertension lead to?
Vascular & renal damage leading to treatment-resistant state
162
What is associated with increased risk of mortality?
Each 2mmHg rise in systolic blood pressure
163
What is the definition of Stage 1 Hypertension?
- Clinic blood pressure (BP) 140/90mmHg or higher and...
| - ABPM or HBPM average is 135/85mmHg or higher
164
What is the definition of Stage 2 Hypertension?
- Clinic BP 160/100mmHg or higher and..
| - ABPM or HBPM daytime average 150/95mmHg or higher
165
What is the definition of Severe Hypertension?
- Clinic BP 180mmHg or higher or...
| - Clinic diastolic BP 110mmHg or higher
166
How do you diagnose Hypertension?
If clinic BP 140/90mmHg or higher, offer ABPM to confirm
167
What does ABPM stand for?
Ambulatory blood pressure
168
What do you need to ensure when using ABPM to diagnose hypertension?
At least 2 measurements per hr during the persons usual waking hrs, average of at least 14 measurements to confirm diagnosis
169
What do you need to ensure when using HBPM to diagnose hypertension?
- 2 consecutive seated measurements, at least 1 min apart
- BP recorded 2x a day for at least 4 days & preferably for a week
- Measurements on 1st day are discarded, average value of all remaining
170
What people would you offer antihypertensive drug treatment?
- Stage 1 hypertension, are ages under 80 & meet identified criteria
- Stage 2 hypertension at any age
171
What would you consider if under 40 with stage 1 hypertension & without evidence of target organ damage, cardiovascular disease, renal disease or diabetes?
- Specialist evaluation of secondary causes of hypertension
| - Further assessment of potential target organ damage
172
How can you monitor drug treatment?
Clinic BP below:
- 140/90mmHg <80yrs
- 150/90mmHg >80yrs
173
How should you monitor drug treatment for people identified as having "white-coat effect"?
ABPM or HBPM, below:
- 135/85mmHg <80yrs
- 145/85mmHg >80yrs
174
What is definite as "white-coat effect"?
Discrepancy of more than 20/10mmHg between clinic & average daytime ABPM or average HBPM blood pressure measurements at the time of diagnosis
175
What is the drug treatment for hypertensive patients aged under 55yrs?
Step 1: ACE inhibitor/Angiotensin II receptor blocker (ARB)
Step 2: ACE/ARB + calcium-channel blocker (CCB)
Step 3: ACE/ARB + CCB + Thiazide-like diuretic
Step 4: all of above + consider further diuretic or alpha/beta-blocker
176
What is the drug treatment for hypertensive patients aged over 55yrs or black person of African/Caribbean origin?
Step 1: Calcium-channel blocker (CCB)
Step 2: ACE inhibitor/Angiotensin II receptor blocker (ARB)
Step 3: ACE/ARB + CCB + Thiazide-like diuretic
Step 4: all of above + consider further diuretic or alpha/beta-blocker
177
What are 2 additional recommendations for hypertension treatment?
1. Lifestyle interventions
| 2. Patient education & adherence
178
What 2 things control blood pressure?
1. Blood volume
| 2. Wall tension
179
Describe how blood volume controls blood pressure?
- Osmolality monitored by osmoreceptors in hypothalamus
| - Mediated by solutes, mainly NaCl
180
Describe how wall tension controls blood pressure?
- Baroreceptors (stretch)
- Atrial natriuretic peptide (ANP)
- Juxtaglomerular apparatus
181
Where are the low stretch baroreceptors located?
Atria & pulmonary vessels
182
Where are the high stretch baroreceptors located?
Aortic archm carotid sinus & juxtaglomerular apparatus
183
Where is Atrial Natriuretic Peptide found?
Atrial myocytes
184
How can sodium and water be excreted (2)?
- Dilating afferent arteriole of glomerulus
| - Suppressing ADH & renin
185
Describe the 3 parts to juxtaglomerular apparatus?
1. Macula densa cells of distal convoluted tubule monitor sodium
2. Granular cells of the afferent arteriole monitor stretch
3. Sympathetic activity
186
Is renin an enzyme or hormone?
Enzyme so rate limiting step
187
What does renin do?
Converts angiotensinogen into antiotensin I
188
What converts angiotensin I into angiotensin II?
Angiotension converting enzyme (ACE)
189
How does angiotensin II hormone raise blood pressure?
- Vasoconstricting arterioles
- Stimulating aldosterone production from adrenal cortex
- Stimulating thirst centre
- Stimulating ADH release
190
How do ACE inhibitors work?
Prevents formation of angiotension II leading to vasodilatation & decrease BP
191
What does ACE inhibitors bind to?
Tissues & plasma so slow elimination by glomerular filtration
192
What are the potential side effects of ACE inhibitors?
- 1st dose hypotension rare in essential hypertension
- Dry irritating cough due to accumulation of bradykinin
- Hyperkalaemia mediated by reducing of aldosterone
193
How do thiazide diuretics work?
Acts on proximal part of distal convoluted tubule, increase sodium excreting & urine volume leading to reducing in blood volume
194
What is the major effects of thiazide diuretics?
Decrease peripheral resistance due to subtle alterations in the contractile responses of vascular smooth muscle
195
What are the potential side effects of thiazide diuretics?
- Hypokalaemia
- Hyperuricaemia (risk of acute gout)
- Hyperglycaemia (risk of new onset diabetes)
- Hypercalcaemia
- Erectile dysfunction
- Thrombocytopaenia & skin rashes
196
How does Calcium channel blockers work?
Reducing calcium influx into vascular smooth muscle cells & promoting vasodilatation, also direct action on cardiac & GI muscle cells
197
What group of calcium channel blockers are commonly used in hypertension?
Dihydropyridine derivates
198
What are the potential side effects of calcium channel blockers?
- Headache & flushing due to dilatation
- Tachycardia due to reflex activation of sympathetic system
- Ankle swelling due to preferential pre capillary arteriolar vasodilatation
- Gym hypertrophy
199
How do beta blockers work?
Antagonise sympathetic system or circulating catecholamines at beta-1 receptors in heart, kidney, beta-2 lung, peripheral blood vessels & skeletal muscles
200
What are the potential side effects of beta blockers?
- Bronchospasm
- Bradycardia
- Peripheral vasoconstriction
- TATT reduced cardiac output
- Masking hypoglycaemia in IDDM (blunting of sympathetic response)
- Hyperglycaemia (risk of onset diabetes)
201
What is Bicarbonate?
- Extracellular anion
| - Principle buffer of ECF (and blood)
202
What is pH equal to?
HCO-3/pCO2
203
What is CO2 regulated by?
Respiratory system
204
How is H+ added to the body?
Diet & metabolism
205
What is HCO-3 regulated by?
Kidneys
206
How is HCO-3 lost?
Faeces each day
207
What 3 actions does the Kidneys do?
1. Bicarbonate filtration
2. Bicarbonate reabsorption
3. Bicarbonate regeneration by titratable acid excretion, ammonium excretion
208
What is the pH at the start of the proximal tubule?
7.4
209
What is the glomerular filtration rate?
180 litres/day
210
What is the normal plasma bicarbonate?
24 mmol/l
211
Where is bicarbonate freely filtered into?
Bowman's capsule
212
How much filtered bicarbonate is reabsorbed in the proximal convoluted tubule?
85-90%
213
How much filtered bicarbonate is reabsorbed in the distal convoluted & collecting tubule?
Remaining 10-15%
214
What is the 3 ion processes common to both distal & proximal convoluted tubule?
- H+ pass into tubular lumen from the cell
- CO2 pass into cells from the tubular lumen
- HCO3 pass into blood from the cell
215
What allows the movement of H+ into tubular lumen in proximal reabsorption?
Secondary active Na/H transport on the apical membrane
216
What ion allows the movement of HCO3 into blood in proximal reabsorption?
Na moving into blood
217
What allows the movement of H+ into tubular lumen in distal reabsorption?
H+ active transport mediated by ATP
218
What ion allows the movement of HCO3 into blood in distal reabsorption?
Cl- moving into cell
219
Acid is _______ produced?
Continually
220
What is the buffering system?
When protons consume bicarbonate
221
Where will the bicarbonate be raised during bicarbonate regeneration?
Renal vein to a level higher than in the artery
222
What are the 2 processes for bicarbonate regeneration?
1. Titratable acid excretion (constant)
| 2. Ammonium excretion (increase markedly)
223
Describe the Titratable acid excretion?
- Protons bufferent by non-bicarbonate buffers esp. phosphate
- Steep inward directed sodium gradient
224
How to non-bicarb buffers enter the lumen during titratable acid excretion?
By filtration
225
What is the equation for Titratable acid excretion?
H+ + HPO4 --> H2PO4-
226
What are the 3 other buffers in the urine?
- Urate
- Creatinine
- Beta-hydroxybutyrate
227
At plasma pH of 7.4 what is the % of monoprotic form?
80%
228
Describe ammonium excretion?
- Derived from glutamine
| - Ammonium excretion can increase dramatically when faced with acidaemia
229
When does renal compensation occur?
Primary respiratory disorder
230
Describe the 6 steps to Respiratory Acidaemia?
1. Rise in pCO2
2. Parallel change inside the renal tubule cells
3. Intracellular acidaemia
4. Increase uptake & use of glutamine & hence ammonium excretion
5. Increasing bicarbonate regeneration
6. Low intracellular pH increases tubular proton secretion & ensures optimum reabsorption of bicarbonate
231
Describe the 5 steps to Respiratory Alkalaemia?
1. Fall in pCO2
2. Parallel change inside renal tubule cells
3. Intracellular rise in pH
4. Proton secretion falls
5. Bicarbonate reabsorption falls
232
What are the factors which increase bicarbonate reabsorption & regeneration?
- Increasing pCO2, H+, angiotensin II, aldosterone
- Decreasing ECF volume
- Hypokalaemia
233
What are the factors which decrease bicarbonate reabsorption & regeneration?
- Decreasing pCO2, H+, angiotensin II, aldosterone
- Increasing ECF volume
- Hyperkalaemia
234
What does decreasing ECF volume/ increasing angiotensin II do?
- Stimulates sodium reabsorption
- Stimulates activity of Na/H exchange mechanism
- Ratio bicarb/H+ in tubular lumen falls
- Excess H+ in tubules
- Bicarb fully reabsorbed & new bicarb forming
235
What 4 things can happen when kidney function is impaired?
- Renal failure
- Damage to glomerulus & tubule
- Will result in metabolic acidaemia
- Decrease in ammonium secretion by tubule
236
How common are the different durations of UTI's?
- Single/isolated attack (90%)
| - Recurrent attacks (10%)
237
What are the different types of recurrent attacks of UTI's?
- Relapse (20%)
| - Reinfection (80%)
238
What are the associated diseases of complicated UTI's?
- Diabetes mellitus
- Sickle cell disease/trait
- Analgesic abuse
239
What are the causes for abnormal excretion urography/CT urogram in complicated UTI's?
- Stones
- Obstruction
- Polycystic kidneys
- Vesicoureteric reflux
240
What do complicated UTI's increase the risk of?
Kidney damage & septicaemia
241
What are the bacterial attributes which favour UTI's?
- Capsular antigens
- Hemolysins
- Urease
- Adhesion to uroepithelium
- Introital colonisation
242
What are the host factors which favour UTI's?
- Renal calculi
- Ureteric reflux
- Tumours in/adjacent to urinary tract
- Pregnancy, bladder stones
- Incomplete bladder emptying (residual urine)
- Loss of sphincter control
- Prostatic hypertrophy
- Short urethra in women
- Catheterisation
243
What is the most common cause of UTI's?
E. coli
244
What are the different serogroups of Uropathogenic E. coli?
- O (somatic)
| - K (capsular)
245
What does UPEC stand for?
Uropathogenic E. coli
246
What are the 3 virulence factors for UPEC?
- Fimbriae (adhesions
- K antigen
- Haemolysin
247
What are the 2 types of fimbriae (pili) on E. coli?
- Type 1
| - Type P
248
What is the bacterial response to adhesion?
- Iron acquisition machinery activated via siderophores
- Stimulates growth & reproduction
- Once a monolayer has formed a biofilm may develop
249
What can happen to bacteria with type 1 fimbriae?
Internalised in phagocytes & epithelial cells
250
Describe the E. coli K antigen?
- Polysaccharide
- Forms micro-capsule
- Confers resistance to phagocytosis
251
Describe the E. coli haemolysin?
- Cytolytic exo-protein
- Damages tissue membranes in vivo
- Causes kidney damage
252
Describe Proteus Mirabilis?
- Gram negative
- Facultative anaerobe
- Bacillus
- Peritrichous flagellae
- Produces urease
- Swarming ability
253
What are the 2 gram negative bacteria which can cause UTI's?
1. Escherichia coli
| 2. Proteus mirabilis
254
Describe Staphylococcus saprophyticus?
- Gram positive
- Coagulase negative
- Normal microbiota of female perineum & vagina
- Sexual activity increases risk of UTI
- Commonly causes community aquired UTI's
- Symptomatic cystitis
255
What are the 3 other causes for UTI's?
1. Candidia albicans
2. Trichomonas vaginalis
3. Schistosoma haematobium
256
Describe Candida albicans?
- Diploid fungus
- Commensal
- Candidiasis (thrush)
- Important opportunistic pathogen in immunocompromised
- Associated with antibiotic use
257
Describe Trichomonas vaginalis?
- Protozoan
- Pear-shaped flagellate
- T. vaginalis is pathogenic
- Other species are commensal
- Trichomoniasis
- Less common in males
258
What pH does Trichomonas vaginalis prefer?
~ 6.0
259
Describe Schistosoma haematobium?
- Trematode worm
- Schistosomiasis
- Contaminated water
- Access through skin
- Matures in liver
- Eggs travel to & penetrate bladder
260
What is the treatment for Schistosoma haematobium?
Praziquantal
261
What does MSU stand for?
- Mid-stream specimen of urine
| - Significant bacteriuria >10x5 per ml
262
What does CSU stand for?
- Catheter specimen of urine
| - Significant bacteriuria, lower number of micro-organisms than MSU
263
When would you see bacteria in suprapubic aspiration of bladder urine?
Schistosoma haematobium & other rare occasions
264
What 2 readings show infection in a urine dipstick test?
- Leukocyte esterase
| - Nitrite
265
What are the host defences?
- Urine (osmolality, pH)
- Sloughing of epithelial cells
- Urine flow & micturition
- Mucosal inhibitors of bacterial adherence
- Complement activation
- Inflammatory response
- Immune responses
- Commensals
266
Give an example of proanthrocyanidins and what they do?
- Cranberry juice
| - Prevent E. coli from adhering to urinary tract epithelial cells by affecting the surface properties of bacteria
267
What are the 6 potential oral antibiotics for UTI's?
1. Co-trimoxazole
2. Nitrofurantoin
3. Nalidixic acid
4. Co-amoxiclav
5. Trimethoprim
6. Ciprofloxacin
