GIT case 5-9 Flashcards
1
Q
prostate gland fluid secretion contents
A
calcium, citrate ion, phosphate ion, clotting enzyme, profibrinolysin
slightly alkaline
2
Q
Lower urinary Tract symptoms
A
- storage symptoms: frequency, urgency, nocturia, urge incontinence
- voidance symptoms: dysuria, hesitancy, poor stream, terminal dribbling, sensation of incomplete emptying
3
Q
micturition mechanisms
A
- urethral relaxation before detrusor contraction
- simultaneous relaxation of pelvic floor muscles
- “funnelling” of bladder neck to facilitate flow of urine into proximal urethra
- detrusor contration occurs to forcefully expel urine
- -> underlying activity:
- increase parasympathetic neuronal activity: removal of central inhibition
- voiding initiated by pontine medullary centres
4
Q
different types of incontinence
A
- urge
- overflow (obstruction): dangerous because can build up and cause back flow
5
Q
How to measure LUTS
A
International Prostate Symptoms Score IPSS: sefull to see changes over time
6
Q
examination for prostate (+ LUTS)
A
- abdominal and genitals (palpable bladder, phimosis)
- DRE
7
Q
investigations for prostate
A
-UEs, creatinine, eGFR
-PSA
-mid stream urine for infection/haematuria
(-ultrasound urinary tram-kidney and bladder residual volume)
8
Q
prostate function
A
- antegrade ejaculation
- contributes to 25% ejaculate volume
- sperm nutrition, milieu to thrive, antimicroial (Zn, selenium)
- PSA enzyme for semen coagulation and liquefaction
9
Q
pathogenesis of benign prostate hyperplasia
A
- trauma from voiding bladder causes damage to urethra in transitional zone: produces inflammatory response: local enlargement of cells + lack of apoptosis
- proliferation of prostate glands, smooth muscle, connective stroma
-age and testosterone are important
10
Q
alpha adrenergic receptors in prostate
- location
- type
A
- alpha-1 adrenergic receptors
- mainly neck of bladder
11
Q
alpha 1 blockers
- names
- advantages
- SE
A
- tamsulosin (flomax)
- alfuzosin (Xatral)
- Doxazosin (Cardura)
advantages:
rapid onset, safe, doesn’t alter PSa, symptoms improvemet maintained
SE: postural hypertension, retrograde ejaculation, headaches (maybe more)
12
Q
formation, storage and release of thyroid hormones
A
- iodide topping (active transport from blood into cytosol by Na+/I- cotransport)
- synthesis of thyroglobulin (in RER, modified in Golgi complex and packaged into secretory vesicles) and exocytosis into follicular lumen
- oxidation of iodide: 2I- –> I2 and pass into follicle lumen
- iodination of tyrosine: T1 or T2 –> TGB + iodine atoms = colloid
- coupling of T1 and T2: T3 or T4
- Pinocytosis and digestion of colloid: merge with lysosomes in follicular cells : digestive enzymes break down TGB and cleave T3/T4
- secretion of thyroid hormones: diffusion into blood (lipid soluble)
- transport in blood: combine wit TBG (thyroxine-binding globulin)
13
Q
actions of thyroid hormones
A
- increase basal metabolic rate: stimulate use of cellular oxygen to produce ATP: increase of metabolism of carbohydrates, lipids and proteins
- additional Na+/K+ ATPases synthesis: calorinergic effect (increase use of ATP and more heat produced)
- stimulation of protein synthesis + increase use of fatty acids and glucose (for ATP) + stimulates lipolysis, cholesterol excretion
- up regulation of beta receptors: increase HR, BP
- accelerate body growth, especially nervous and skeletal systems
14
Q
what is basal metabolic rate
A
rate of oxygen consumption under standard or basal conditions (awake, at rest and fasting)
15
Q
control of thyroid hormone secretion
A
- low blood levels of T3(/T4) or low metabolic rate stimulate hypothalamus to secrete TRH
- TRH stimulates thyrotrophs to secrete TSH (in pituitary gland)
- TSH stimulates all aspects of thyroid follicular cell function
- thyroid gland release T3 and T4
- elevated T3: negative feedback inhibition of TRH and TSH
16
Q
calcitonin production: where and how, actions
A
parafollicular cells
high levels of Ca2+ stimulates calcitonin (controlled by neg feedback)
inhibits osteoclasts activity (bone resorption): decrease blood calcium and phosphate levels
17
Q
effect of parathyroid hormone on bone
A
increase number and activity of osteoclasts: increase bone resorption: increase Ca2+ and HPO42- (phosphate) release in blood
18
Q
effect of parathyroid hormone on kidney
A
- slows rate that Calcium and magnesium are lost in urine
- increases loss of phosphate in urine
- promote calcitriol formation (active form of vit D): increase rate of calcium, phosphate and magnesium absorption in GIT
19
Q
adrenal glands structure
A
adrenal cortex: zona glomerulus, fasciculata, reticular
adrenal medulla
20
Q
secretions of adrenal cortex and adrenal medulla
A
zona glomerulus: mineralicorticoids
zona fasciculata: glucocorticoids
zona reticularis: androgens
adrenal medulla: noradrenaline and adrenaline
21
Q
thyroid hormone receptors
A
- TR alpha 1 and 2
- TR beta 1 and 2
TR alpha 2 does not bind T3 (the rest of the receptors binds with more affinity to T3)
TR beta 2 only found in the brain (the rest are found throughout the body)
22
Q
cellular action of thyroid hormones
A
- thyroid hormones receptors found in nucleus (form dimers either between 2 hormone receptors or with retinoid acid receptor)
- in absence if thyroid hormone, TR receptor binds to DNA and represses gene transcription (with co-repressor), in presence of thyroid hormone, co-repressors replaces by co-activators: gene transcription activated
23
Q
bodily effects of thyroid hormone
A
cardiovascular: increased cardiac output, increase HR and stroke volume, decreased systemic vascular resistance, increased systolic pressure
metabolic effects: increase BMR, increased oxygen consumption, increased thermogenesis, increased protein turnover
neurological effects: enhances wakefulness, memory, alertness, reflexes, normal emotional tone
growth and development: fatal growth neural development, normal bone growth and birth, normal tooth development
Reproduction: essential for normal reproductive function
24
Q
propanolol
A
beta blocker:
use: ischemic heart disease, chronic heart failure, atrial fibrillation, supra ventricular tachycardia, hypertension
MOA: reduce force of contraction and speed of conducting in the heart (block beta1 adrenoreceptors)
25
what enzyme deiodinates T4 to T3
iodinase
26
action of thyroid peroxidase (TPO)
iodide ions to iodine atoms
27
MOA of carbimazole
inhibit TPO
28
MOA of propylthiouracil
inhibits TPO + stops conversion from T4 to T3
29
blood supply of kidney
renal artery --> segmental --> interlober --> arcuate --> cortical radiate --> afferent arteriole --> glomerulus --> efferent arteriole --> peritubular capillaries/vasa recta --> cortical radiate vein --> arcuate --> interlobal --> segmental --> renal
30
three layers of glomerulus
- endothelium
- basement membrane
- podocytes
31
charge barrier of glomerulus
glycocalyx (heparin sulfate)
32
auto regulation mechanisms of kidney
- myogenic
| - tubuloglomerular feedback
33
how do you measure GFR (renal clearance)
volume of plasma which is cleared of substance x per uni of time: (urinary concentration of x * urine volume per unit time)/ plasma concentration of x
34
how much sodium reabsorbed in different parts of nephron
PCT: 67%
loop of Henle: 25%
DCT and CD: 8%
35
what are the four processes of Motivational Interviewing?
- engaging
- focussing
- evoking
- planning
36
how do you measure proteinuria?
- PCR (protein:creatinine ratio)
| - ACR (albumin:creatinine ratio)
37
stages of injury of diabetic nephropathy
```
hyperfiltration
microalbuminuria
macroalbuminuria
proteinuria
declining renal function
```
38
pathology of diabetic nephropathy
```
-glomerular:
GBM thickening
mesangial cell expansion
nodular sclerosis
advanced sclerosis
```
- tbulo-interstitial
- vascular
39
treatment goals for diabetic nephropathy
-glycaemic control
-BP control
-RAAS bockade
-lipid lowering
-reduce other CV risks
(SGLT2 inhibitors)
40
renal replacement therapy
peritoneal dialysis
haemodialysis dialysis
haemofiltration dialysis
transplant
41
pathogenesis of viral hepatitis
non-cytopathic virus:
- immune-mediated hepatocyte damage
- Ag recognition by cytotoxic T cells causing apoptosis
- hemokine driven recruitment by Ag-non-specific cells
42
which hep is only acute
hep A
43
when do you define hepatitis as chronic
persistence of infection > 6 months
44
hep A virus
- name/types
- incubation period
- complications
- diagnosis
```
-RNA virus
picornavirus
-30 days (4-6 weeks)
- prolonged cholestasis, liver failure
-acute infection HAV IgM, recovery/vaccination: HAV IgG
```
45
hep E virus
- name/types
- incubation period
- genotypes
- complications
- diagnosis
- RNA virus herpevirus
- 40 days
- genotype 1,2 waterborne outbreaks, genotype 3,4 zoonotic
- higher mortality in cirrhotics, pregnant women, acute neurological syndromes, type 3, 4 can become chronic in immunosuppressed patients
- HEV IgM (Hep E IgG, HEV RNA blood, stool)
46
hep B virus
- name/types
- incubation period
- complications
- diagnosis
- treatment
- DNA virus (hepadnaviridae)
- 75 days (6 weeks to 6 months)
- end stage liver disease (cycles of inflammation and repair lead to fibrosis) and liver cancer
- HBsAg, core Ab: chronic infection, core Ab: previous exposure
- interferon, tenofovir, entecavir
47
hep Delta virus
- name/types
- infections routes
- complications
- diagnosis
- treatment
- defective RNA virus (needs Hep B to replicate)
- blood, sexual: simultaneous or superinfection with HBV (uses surface antigen for enveloppe)
- severe hepatitis, cirrhosis, hepatocelullar carcinoma
- hep delat IgM, IgG, HDV RNA
- PEG IFN
48
hep C virus
- name/types
- incubation period
- complications
- diagnosis
- treatment
- RNA Flavivirus
- 2 weeks- 6 months
- chronic infection
- HCV Ab pos and HCV RNA pos: chronic infection, HCV Ab pos and HCV RNA neg: prior exposure
- treatable because life cycle takes place in cytoplasm (no viral reservoirs)
49
liver zone 1
periportal
- aa catabolism
- gluconeogenesis
- cholesterol synthesis
--> requires a lot of oxygen
50
liver zone 3
pericentral
- lipid synthesis
- ketogenesis
- glutamine synthesis
- drug metabolism
51
where does fibrosis start in the liver
zone 3
52
space between sinusoid and hepatocyte
space of Disse
53
bile composition
- bile acids/salts (+phospholidpids and cholesterol)
- bilirubin (conjugated)
- metabolites of hormones and drugs
- heavy metal ions
- electrolytes (HCO3- and wate)
54
synthesis of bile acids/salts
cholesterol --> chalice acid --> (bacteria) deoxycholic acid + glycine (conjugated)
cholesterol--> chenodeoxycholic acid --> (bacteria) lithocholic acid + taurine (conjugated)
55
apical secretion of bile acids/salts transporters
- BSEP (bile salt export pump)
- MRP2 (multidrug resistance-associated protein 2)
- -> both ABC transporters (ATP binding cassette)
56
lipid soluble bilirubin
unconjugated
57
where is conjugated bile salts absorbed in GIT and by which transporters
terminal ileum
ASBT (Na+ bile salt cotransporter
OST (organic transporter)
58
flippase action
maintains asymmetry in phospholipids on the outside and inside of cells: important for signalling
59
heme breakdown
heme --> (heme oxygenase)
biliverdin --> )biliverdin reductase)
bilirubin
by phagocytosis
60
bilirubin excretion
conjugated bilirubin --> (baceria) urobilinogen (unconjugated and colourless) --> stercobilin (brown or urobilin (yellow)
61
epithelial cells of bile duct
cholangiocytes
62
fluid secretion by cholngiocytes
```
30-50% of hepatic bile
-secondary active transport of Cl- and HCO3-
-paracelular Na+ transport
-isosmotic water flow
(secreted by secretin, VIP and glucagon)
```
63
reabsorption by gall bladder epithelium
- Na+ with NHE (secondary active transport)
- Cl- reabsorbed for HCO3- + H+ secretion
- isosmotic H20 absorption
64
bilirubin and drug binding to proteins
displaces it so more free drug
65
phases of metabolism of drugs
phase 1: functionalisation (produce/uncover chemically reactive functional groups i.e. oxidation): pharmacological activation
phase 2: conjugation (water soluble and easily excreted: pharmacological inactivation
66
CYP polymorphisms: different types of metabolisers and genes associated
poor (homozygous for defective gene)
intermediate (heterozygous for defective gene)
extensive (homozygous for functional gene)
ultra-rapid (extra copies of functional gene)
67
paracetamol metabolism
1. paracetamol --> glucuronide and sulphate conjugates of -OH group --> inactive metabolite
2. paracetamol --> N-hydroxylation CYP450 --> re-arragemen: N-acetyl-p-benzoquinone imine --> glutathione conjugation --> inactive metabolite
(N-acetyl-p-benzoquinone mine can cause hepatotoxicity and cell death)
68
illegal intoxication limit for alcohol
0.08 g/dL
69
average elimination rate of alcohol
0.015 g/dL/hr
70
non-alcoholic fatty liver disease
- fatty change
- non-alcoholic steatohepatitis (NASH)
- fibrosis
- cirrhosis
71
cirrhosis what is is and causes and effects
- disease of all the liver with parenchymal nodule and surrounding fibrosis
- causes: alcohol, liver, metabolic diseases, autoimmune
- effects: liver failure, portal hypertension and HCC
72
what problems happen with liver failure?
protein synthesis: low albumin
coagulation factors: bleeding
jaundice
encephalopathy: confusion
73
what problems happen with portal hypertension
ascites
varices
splenomegaly
74
what signs with hepatocellular carcinoma
raised serum alpha-fetoprotein levels
75
which organs sense glucose and what do they release
- brain: sympathetic/parasympathetic
- gut: incretins
- beta cells: insulin
76
ER stress on beta cells effect
protein misfolding and apoptotic cell death + accumulation of amyloid fibrils
77
what are normal levels of fasting glucose and post prandial?
fasting: 4-<6 mol/L
post prandial <7.8 mmol/L
78
gastroperesis and diabetes
slower gastric emptying: high levels of glucose can damage vagus nerve
79
epsilon cells of pancreas production
gherlins: increase appette
80
PP cells of pancreas production
pancreatic polypeptide: promote GI fluid secretion and satiety
81
glycation
covalent bonding of a sugar molecule to a protein or lipid molecule (ie HbA1c)
82
insulin receptor mechanism
2 insulin molecules binds to alpha chains leading to autophosphorylation of tyrosine kinase within beta chain: recruit adaptor proteins (i.e. insulin receptor substrate protein) with increases PI3K activity
--> insertion of GLUT in cell membrane
83
incretins
- names
- function
- GIP (glucose dependent insulinotropic polypeptide)
- GLP-1 (glucagon like peptide-1)
functions: reduce glucagon secretion, increase insulin secretion, satiety, reduce glucose synthesis in liver, slow gastric emptying
84
dysregulation of incretins in diabetes
GLP-1 secretion is reduced and sensitivity of beta cells to it is decreased
GIP response is reduced
85
neuroglycopenia: what is in and when do you experience it
shortage of glucose in brain
| at 3 mmol/L
86
at what level of glucose do you experience sever neuoglycopenia?
1 mol/L
87
treatment options for DM
- insulin secratogogues: GLP-1 receptor antagonists, DPP4 inhibitors, sulphonylureas/meglitinides
- insulin sensitisers: hiazolinadions, biguanides
- decrease glucose reabsorption in kidney: SGLT2 inhibitors
- slow glucose absorption: alpha-glucosidase inhibitors
88
what is adiponectin
protein in adipocyte: insulin sentising and anti-atherogenic
89
what is resistin
neutralising antibodies: reduce insulin resistance
90
adipose tissue and IL6
- correlation between IL6 and insulin resistance
| - viscerl fat secretes 2x more IL6 than subcutaneous fat
91
adipose tissue: endocrine release
```
adiponectin
TNFalpha
Resisting
leptin
interleukin 6
```
92
effects of leptin
- muscle: increase glucose uptake and glycogenolysis
- liver: decrease gluconeogenesis, increase glycogenolysis, increase beta oxidation
- adipose: increase lipolysis, decrease lipogenesis
- beta cells: decrease insulin synthesis and secretion
- brain (hypothalamus): inhibition of feeding and increase of sympathetic output
93
PPAR gamma activation effects
-increase adipogenesis --> decrease leptin and TNFalpha, increase FA disposal and glucose uptake --> increase insulin receptor function -->increase beta cell function and decrease HGO, glycogenolysis
94
PPAR
| what it stands for and what type of receptor
peroxidase Proliferator Activated Receptor
nuclear hormone receptor family, dimerises with retinoid X receptor (RXR)
95
BMI values
- 18.5-24.9: healthy weight
- 25-29.9: overweight
- 30-34.9: obesity 1
- 35-39.9: obesity 2
- +40: obesity 3
96
body weight distribution names
gynaecoid: lower fat obesity (doesn't have CV risks)
android: upper fat obesity
97
insulin release from beta cell mechanism
glucose enters cell --> increase ATP which blocks K+ ATP channel --> incur intracellular ca2+ --> insulin exocytosis
98
tests for DMT1 diagnosis
- GAD antibodies
- Islet cell antibodies
- insulin antibodies
- C peptide/Insulin/glucose levels
99
treatment of DKA
```
IV fluid
potassium replacement
insulin replacement
replacement of electrolytes
LMWH, antibiotics
```
100
biguanides MOA
increase sensitivity to insulin
101
thiazolidinediones MOA
insulin sensitiser: activated PPARgamma: increase insulin action
102
example of TZD
pioglitazone
103
example of sulphonylurease
glicazide
104
DDP-4 inhibitors MOA
stimulate insulin and inhibit glucagon (glucose dependent)
105
alpha 1 blockers examples
tamsulosin
alfuzosin
doxazosin
106
what converts testosterone to dihydrotestosterone
5 alpha reductase
107
example of 5 alpha reductase inhibitors
finasteride
| dutasteride
108
surgical options for prostate cancer
transurethral resection of prostate (TURP)
Holmium enucleation of prostate (HoLEP)
109
red flags with the prostate
```
urinary incontinence
renal impairement
haematuria
recurrent urinary infections
raised PSA
```
110
which nerves supply the bladder and with receptor/neurotransmitters associated
- pelvic nerve (parasympathetic): ACh/M3 receptor (+)
- hypogastric (sympathetic): NA/beta3 receptor (-) and in urethra: NA/alpha1 receptor (+)
- pudental nerve (somatic): ACh/nicotinic receptor (+)
111
three histological varieties in kidney malformation
- hypoplasie (too few nephews)
- dysplasia (undifferentiated kidney sometimes with cysts)
- agenesis (absent kidneys)
112
three histological varieties in kidney malformation
- hypoplasia (too few nephews)
- dysplasia (undifferentiated kidney sometimes with cysts)
- agenesis (absent kidneys)
113
renal coloboma syndrome
optic nerve malformation (blindness)
smal, malformed kidneys (kidney failure)
PAX2 transcription factor
114
causes of acquired kidney failure
- pre-renal causes: shock, cardia and liver failure
- intrinsic kidney disease: glomerular and tubular disease
- post-renal causes: urinary flow impairment
115
different zones of the prostate
transitional zone
central (surrounding ejaculatory duct)
peripheral
116
how many men are diagnosed with prostate cancer in the UK
1/8
117
symptoms of prostate cancer
LUTS
metastatic (ie pain)
systemic (fatigue, weight loss)
118
different types of prostate biopsy
- transrectal ultrasound guided (TRUS) biopsy (through rectal wall with ultrasound)
- template biopsy (transperineal)
119
what scoring system do you use for prostate cancer
Gleason Score
| score from 3-5 are considered cancerous
120
action of TPO
thyroglobulin + I- --> thyroglobulin containing thyroid hormone (in coloid)
121
which thyroid hormone has the longer half life
T4
122
what can fT4 be turned into
T4 --> T4 --> rT3 or T3
123
what can fT3 be turned into
T3 or T2
124
What type of hormone is thyroid hormones
steroid
125
where is T4 converted into T3
liver and kidney
126
primary hypothyroidism aetiology
- autoimmune thyroiditis
- drugs (amiodarone, iodides, lithium)
- iodide deficiency
- congenital
- post-ablative radioiodine/post-operative
127
secondary/tertiary (hypopituitarism/hypothalamic) hypothyroidism aetiology
- pituitary adenoma, congenital deficiency, irradiation
| - sarcoid, infection
128
investigations in hypothyroidism
- thyroid function tets
- nomochromic, normocytic anaemia
- macrocytosis, mixed dyslipidaemia
- increase serum AST, creatine kinase
- hyponatremia
129
aetiology of hyperthyroidism
- Grave's disease
- toxic nodules
- pituitary adenoma or thyroid resistance syndrome
- trnasiet
- pharmacological
130
investigations primary hyperthyroidism
- ultrasound: homogenous (Graves) or heterogenous (NMG)
| - uptake sacan (homogenous or isolated 'hot nodules')
131
treatment of hyperthyroidism
thionamide
| radioiodine or surgery
132
what are symptoms that are specific to Grave's disease
all the hyperthyroidism symptoms +
- tyroid eye disease/Graves orbitopathy
- peritibial myxoedema
133
What is Graves orbitopathy/thyroid eye disease
inflammation of extra ocular muscles: increase retro-orbital pressure --> proptosis
+ glycosaminoglycan deposits and fibrosis
134
problems of pregnancy and Grave's disease
- spontaneous abortion
- premature labour
- small birth weight
- congestive cardiac failure
- pre-eclampsia
135
HPA axis
circadian rhythm + stress --> (hypothalamus) CRH --> (anterior pituitary) ACTH --> (adrenal cortex) cortisol --> (neg feedback on hypothalamus and anterior pituitary)
136
what is cortisol transformed into in the peripheral tissues
cortisone
137
over production of mineralocorticoids syndrome
Conn syndrome
138
over production of glucocorticoid syndrome
Cushing syndrome
139
secondary adrenal gland under production cause and effect
hypopituitarism, loss of ACTH (aldosterone secretion preserved)
140
what increase blood glucose levels
glucagon, catecholamines, cortisol, groth hormones
141
drugs that prevent production of cortisol
metyrapone
ketoconazole
mitotane
142
hormones that regulate BP
- angiotensin 2
- aldosterone
- cortisol
- catecholamines
- calcium/PTH
- growth hormones
143
tumour of adrenal medulla
pheochromocytoma
144
Addison's diease
primary hypoadrenalism: decreased glucocorticoid, mineralocorticoid an sec steroid production
145
(EBM) what is odds
likelihood of an event/outcome occuring
146
how do you calculate odds
nb of individual with outcome/nb of individuals without outcome
147
in regards to odds, when is an event more likely to happen than not
when greater than 1
148
when odds ratio (relative odds) used?
used to compare whether likelihood of certain event occurring is same for row groups
149
how do you calculate odds ratio?
odds of outcome in one group/odds of outcome other group
150
fat soluble vitamin absorption
facilitated diffusion and/or endocytosis
151
water soluble vitamins names
B and C
152
water soluble vitamins absorption
```
specific transporters (facilitated and secondary)
B12 by endocytosis
```
153
what are the two types of Chi-square tests
goodness of fit
| test of independence
154
what does the goodness of fit Chi square test test
observed frequency distribution differs from theoretical distribution
155
what does the test of independence Chi square test test
paired observation on two variables expressed in a contingency table, are independent of each other
156
what does false negative and false positive mean
false positive: have positive result but don't actually have the disease
false negative: have negative results but actually have disease
157
what is sensitivity (EBM)
probability of correctly diagnosing a condition (true positives)
158
what is specificity
probability of correctly identifying a non-disease person (true negatives)
159
how do you calculate sensitivity
true positives/ (true positives+ false negatives)
160
how do you calculate specificity
true negatives/ (true negatives + false positives)
161
what is the positive predictive value
probability that disease is present when test is positive
162
how do you calculate the positive predictive value?
true positives/ (true positives + false positives)
163
what is the negative predictive value?
probability that the disease is not present when the test is negative
164
how do you calculate the negative predictive value
true negatives / (false negatives + true negatives)
