Chem Path ✔ Flashcards
(290 cards)
1
Q
Name the 3 forms of Calcium in the body and proportions of each:
A
Free (ionized) - biologically active (50%)
Protein-bound - (40%)
Complexed with citrate/phosphate (10%)
2
Q
what is normal ‘total serum Ca’ levels?
A
2.2-2.6 mmol/L
3
Q
what is the ‘adjusted’ serum Ca?
A
serum Ca +0.02 *(40-serum albumin in g/L)
4
Q
what happens in the body to ensure Calcium hemostasis when low Calcium is detected?
A
dec Ca –> PTH release by parathyroid –> ‘obtain’ Ca from 3 sources (kidney, gut, bones)
5
Q
name of hormone that activates Calcium in the kidney?
A
renal 1-alpha-hydroxlyase activation
6
Q
what does the release of PTH cause?
A
increased bone and renal Ca resorption, increased 1,25 OH vitamin D levels
7
Q
what does increased 1,25 OH Vitamin D cause?
A
increased intestinal Ca absorption
8
Q
what two hormones are involved in calcium homeostasis?
A
PTH & Vitamin D
9
Q
what is the role of PTH in the body?
A
bone & renal Ca resorption
renal Pi wasting
1,25-OH Vitamin D synthesis
10
Q
when cholecalciferol is activated in the liver, what does it become?
A
25-hydroxycholecalciferol (25-OH D3)
11
Q
when PTH stimulates the kidney, what changes happen to 25-OHD3?
A
25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol
12
Q
what is the physiologically active form of vitamin D?
A
1,25 (OH)2 D3
13
Q
what is the pathway of synthesis of Vitamin D?
A
100% of absorbed vitamin D is hydroxlyated at the 25 position by 25-hydroxylase
then 25-hydroxy D is inactive, stored and measured
14
Q
what is the pathway of activation of Vitamin D?
A
1-alpha hydroxylase in the kidney activates 25-hydroxy D into 1,25-OH D3
15
Q
what is 1-alpha hydroxylase and where does it come from?
A
from the kidney, activates vitamin D
16
Q
what is 25-hydroxylase and where is it made?
A
in the liver, hydroxylates vitamin D for storage
17
Q
what is vitamin D deficiency in children vs adults?
A
children - rickets
adults - ostemalacia
18
Q
what are some features of a child with vitamin D deficiency?
A
bowed legs, chostocondral swelling, widened epiphysis at the wrist, myopathy
19
Q
if someone has low Ca, low Pi, raised ALP - what do you suspect?
A
osteomalacia
20
Q
what is the blood chemistry of someone with ostemalacia?
A
low Ca, low Pi, raised ALP
21
Q
what are Looser’s zones?
A
pesudo fractures from ostemalacia
22
Q
what type of medication can induce osteomalacia in adults?
A
anticonvulsants
23
Q
what is the biochemistry in osteoporosis?
A
NORMAL Ca but reduction in bone density
24
Q
what DEXA T score is definitive of osteoporosis?
A
T
25
what DEXA T score is definitive of osteomalacia?
T score between -1 & -2.5
26
if someone has a T score of T
A
27
if someone has a T score of T=-1 on their DEXA scan, what do you suspect?
A. Osteporosis
B. Osteomalacia
C. Paget's Disease
B. Any T score between -1 & -2.5
28
list some causes of osteoporosis in a systematic way:
Lifestyle: sedentary, EtOH, smoking, low BMI/nutritional
Endocrine: hyperprolactinaemia, thyrotoxicosis, Cushings
Drugs: steroids
Others eg genetic, prolonged intercurrent illness
29
name 5 biological (medical) treatments for osteoporosis
1) Vitamin D/Ca
2) bisphosphonates (alendronate)
3) PTH derivative (terparatide)
4) strontium
5) HRT (estrogens)
6) SERMs (raloxifene)
30
name the symptoms of hypercalcemia:
polyuria/polydipsia
constipation
neuro (confusion, seizures, comas)
'bones, stones, moans, groans'
31
at what level of calcium would you see hypercalcemia symptoms?
Ca > 3.0 mmol/L
32
what is the normal hormonal response to hypercalcemia?
PTH suppression
33
what are potential causes of hypercalcemia if PTH is NOT suppressed? (one common, one rare)
primary problem with PTH regulation
common - primary hyperparathyroidism
rare - familial hypocalcuric hypercalcemia (FHH)
34
what are potential causes of hypercalcemia if PTH is suppressed?
common - malignancy
| rare- sarcoid, vitamin D excess, thyrotoxicosis, milk alkali syndrome
35
what is the commonest cause of hypercalcemia?
primary hyperparathyroidism
36
what bone chemistry do you expect to see in primary hyperparathyroidism?
increased Ca
increased/normal PTH (inappropriate!)
decreased serum phosphate
urine increased Ca
37
what is the CaSR and what does it do?
parathyroid - PTH release
| renal - Ca resorption
38
what genetic condition is associated with CaSR mutations?
FHH - higher 'set point' for PTH release leading to some constant mild hypercalcemia
39
what hypercalcemia is associated with malignancy?
humoral hypercalcemia (PTHrp; small cell lung Ca)
bone mets
hematological malignancy
40
what non-PTH driven hypercalcemia causes are there?
sarcoidosis, thyrotoxicosis, hypoadrenalism, thiazide diuretics, excess vitamin D
41
what is the treatment of hypercalcemia?
fluids fluids fluids!
| Treat any underlying cause
42
what are the clinical signs of hypocalcemia?
neuro-muscular excitability
| Chvostek's sign, Trosseau's sign, hyperreflexia, convulsions
43
what causes of hypocalcemia are PTH driven?
surgical (eg post thyroidectomy)
auto-immune hypoparathyroidism
congenital absence of parathyroids (eg DiGeorge's)
Mg deficiency
44
if calcium is low, what do you expect PTH to do?
increase
45
what cause of hypocalcemia can progress to tertiary hypoparathyroidism?
CKD
46
what can CKD progress to with regards to Ca homeostasis?
secondary hypoparathyroidism progression to tertiary
47
what are non-PTH driven causes of hypocalcemia?
```
vitamin D deficiency
CKD
PTH resistance ('pseudohypoparathyroidism')
```
48
what is the key factor of blood chemistry in Paget's disease? (think Ca, ALP, Albumin, PTH....)
elevated alkaline phosphatase
49
bone chemistry of osteoporosis: Ca, Pi, PTH, Vit D, ALP
```
Ca: Normal
Pi: Normal
PTH: Normal
Vit D: Normal
ALP: Normal
```
50
```
Diagnose the Calcium issue from this chemistry -
Ca: Normal
Pi: Normal
PTH: Normal
Vit D: Normal
ALP: Normal
```
osteoporosis
51
bone chemistry of osteomalacia/rickets:
```
Ca: decrease or normal
Pi: decrease or normal
PTH: increase
Vit D: decrease
ALP: increase
```
52
```
Diagnose the calcium issue from this chemistry -
Ca: decrease or normal
Pi: decrease or normal
PTH: increase
Vit D: decrease
ALP: increase
```
ostemalacia
53
bone chemistry of Paget's disease:
```
Ca: normal
Pi: normal
PTH: normal
Vit D: normal
ALP: increase
```
54
```
diagnose the calcium issue from this chemistry -
Ca: normal
Pi: normal
PTH: normal
Vit D: normal
ALP: increase
```
Paget's disease
55
bone chemistry of parathyroid bone disease:
```
(inc. PTH)
Ca: increase
Pi: decrease
PTH: increase/ normal
Vitamin D: normal
ALP: increase or normal
```
56
```
Diagnose the calcium issue from this chemistry -
(inc. PTH)
Ca: increase
Pi: decrease
PTH: increase/ normal
Vitamin D: normal
ALP: increase or normal
```
parathyroid bone disease
57
bone chemistry of renal bone disease
```
Ca: decreased or normal
Pi: increased
PTH: increased
Vitamin D: normal (1 -alpha-hydroxylase is low)
ALP: increased/normal
```
58
Diagnose the calcium issue from this chemistry -
Ca: decreased or normal
Pi: increased
PTH: increased
Vitamin D: normal (1 -alpha-hydroxylase is low)
ALP: increased/normal
renal bone disease
59
name that biochemical abnormality: pH 6.92, PCO2 =3
metabolic acidosis
60
what is the pH and PCO2 in metabolic acidosis?
pH LOW
| PCO2 LOW
61
name that biochemical abnormality: pH 7.70, PCO2 = 3
respiratory alkalosis
62
what is the pH and PCO2 in respiratory alkalosis?
pH HIGH
| PCO2 LOW
63
what is the pH and PCO2 in respiratory acidosis?
pH LOW
| PCO2 HIGH
64
name that biochemical abnormality: pH 6.92, PCO2 = 7
respiratory acidosis
65
what is the pH and PCO2 in metabolic alkalosis?
pH HIGH
| PCO2 HIGH
66
name that biochemical abnormality: pH 7.70, PCO2 = 10
metabolic alkalsosi
67
what does abbreviation ROME stand for in biochemistry values?
Respiratory Opposite
| Metabolic Equal
68
what is normal PCO2 concentration on blood gas?
PCO2 = (approx.) 4 -5
69
what is the formula for calculating osmolality?
Osmo = 2(Na+K) + Urea + Glucose
70
what is formula for calculating anion gap?
AG = (Na+K) - bicarbonate - chloride
| positives minus negatives
71
what is the normal level of lactate?
Normal Lactate < 2.0 mM
72
Definition of type 2 diabetes (in fasting glucose and plasma)?
Fasting glucose > 7.0 mM
GTT with plasma glucose > 11.1 mM at 2 hours
(If the 2 hour value is between 7.8 -11.1 mM then called 'impaired glucose tolerance')
73
how does type 4 renal tubular acidosis cause hyperkalemia?
reduced renin --> less angtiotensins --> less aldosterone --> less potassium secretion --> k+ inc.
74
how do you get type 4 renal tubular acidosis?
end stage diabetic nephropathy
75
how does CKD cause hyperkalemia?
reduced GFR
76
what is a cause of reduced GFR?
CKD
77
how can ACE inhibitors cause hyperkalemia?
less angiotensin II --> less aldosterone --> less potassium secretion in kidneys
78
how can ARBs cause hyperkalemia?
angiotensin receptor blockers block angiotensin II --> less aldosterone --> less potassium secretion
79
how does Addison's disease cause hyperkalemia?
less aldosterone --> less potassium secretion
80
how does aldosterone antagnosists cause hyperkalemia?
block the production of aldosterone --> less potassium secretion
81
what are the biochemical processes to hyperkalemia? (think of 3!)
1) rhabdomyolysis (e,g. crush injuries)
2) acidosis (maintaining electro-neutrality)
3) reduced GFR/renin
82
what are the main causes of hyperkalemia? (think of 4!)
1) renal impairment (CKD, reduced renal excretion)
2) drugs ( ACEi, ARBs, spironolactone)
3) Addison's disease (low aldosterone)
4) rhabdomyolysis
5) acidosis
6) type 4 renal tubular acidosis/diabetic nephropathy
83
what are the 3 main causes of hypokalemia?
1) GI Loss
2) renal loss
3) cellular redistribution
84
what changes will you see in hyperkalemia?
ECG changes: peaked T -waves
85
what are the acute dangers of cocaine use?
cardiac dysrhythmias,
acute heart failure
MI
86
how do you manage a patient with hyperkalemia? (5 parts; include dosage)
1) 10 mL 10% calcium gluconate
2) 50 mL 50% dextrose
3) 10 units of Insulin (with dextrose)
4) nebulized salbutamol
5) treat underlying cause
87
what do loop diuretics do in the loop of Henle?
block sodium, potassium, chloride reabsorption in the ascending loop which leads to increase sodium delivery to the distal nephron (DCT)
88
what is the relationship between Na+ and K+ in the kidney?
Na+ absorbed
| K+ lost
89
4 causes of hypokalemia:
1) GI Loss
2) Hyperaldosteronism (excess cortisol)
3) osmotic diuresis
4) insulin, beta-agonists
5) alkalosis
6) renal tubular acidosis type 1 and type 2
90
what biochemical abnormality does hyperaldosteronism cause?
hypokalemia
91
what biochemical abnormality does alkalosis cause (think Na, Bicarb, K, Cl...)
hypokalemia
92
what biochemical abnormality does renal tubular acidosis type 1 & type 2 cause?
hypokalemia
93
what biochemical abnormality does renal tubular acidosis type 4 cause?
hyperkalemia
94
what biochemical abnormality does insulin cause?
hypokalemia
95
what biochemical abnormality does acidosis cause (think Na, Bicarb, K, Cl...)
hyperkalemia
96
what are the clinical features (presenting symptoms) of hypokalemia?
muscle weakness
cardiac arrthymia
polyuria
polydipsia
97
what are the clinical features (presenting symptoms) of hyperkalemia?
often asymptomatic (may be weak, nauseous, fatigued...)
98
if someone presents with polyuria/polydipsia - what biochemical blood tests do you want to look for?
low potassium
high calcium
(cause resistance to effects of ADH)
99
what screening test would you order in a patient with hypokalemia & hypertension?
aldosterone:renin ratio (would see high aldosterone inhibiting renin; low renin)
100
what endocrine disorder has a high aldosterone:renin ratio: (high aldosterone, low renin)?
Conn's syndrome
101
3 steps of managing a patient with hypokalemia (potassium 3.0-3.5 mmol/L) with doses?
1) oral potassium chloride (2 SandoK tabs TDS, 48 hrs)
2) recheck potassium levels
3) treat underlying cause
102
2 steps of managing a patient with hypokalemia (potassium <3.0 mmol/L) with doses?
1) IV potassium chloride (max rate 10mmol/hr)
| 2) treat underlying cause
103
hyperkalemia is a side-effect of which of the following drugs?
a. Fruosemide
b. Bendrofluoromethazide
c. Salbutamol
d. Ramipril
d. Ramipril (ACE inhibitor)
104
hypokalemia is a side-effect of which diuretic drug(s)?
thiazide
frusemide
salbutamol
105
hypokelaemia is a side effect of which of the following drugs?
a. Spironolactone
b. indomethacin
c. perindopril
d. Fruosemide
frusemide
106
what is the aldosterone - potassium relationship?
aldosterone causes potassium loss
107
what type of diuretic is spironolactone?
potassium-sparing
108
what are the causes of hypovolemic hyponatremia? (4)
diarrhea
vomiting
diuretics
salt-losing nephropathy
109
what are the causes of euvolemic hyponatremia? (3)
hypothyroidism
SIADH
adrenal insufficiency
110
what are the causes of hypervolemic hyponatremia? (3)
cardiac failure
cirrhosis
nephrotic syndrome
111
what is the process by which someone becomes hypovolemic hyponatremic?
reduced ECF volume & reduced sodium --> low blood volume stimulates ADH release --> retain water, sodium concentration drops
112
normal values of Na +?
135 - 145 mmol/L
113
normal values of K+?
3.5 - 5.0 mmol/L
114
normal values of urea?
3.0 - 7.0 mmol/L
115
what tests do you want to do to if someone is euvolemic and hyponatremic?
TFTs
short synacthen test (adrenal insufficiency; acth test)
plasma & urine osmolality (SIADH)
116
sodium low, potassium high, pigmentation, postural hypotension -- name that condition!
Addison's disease
117
diagnosis of SIADH:
plasma osmolality LOW
urine osmolality HIGH
no hypothyroidism or adrenal insufficiency
118
causes of SIADH
```
brain pathology
lung pathology
drugs (SSRI, TCA, opiates, PPIs,)
tumors
surgery
```
119
what investigations do you do in suspected diabetes insipidus and why:
```
serum glucose (exclude diabetes mellitus)
serum potassium (exclude hypokalemia)
serum calcium (exclude hypercalcemia)
plasma & urine osmolality
water deprivation test
```
120
what does ADH do?
acts on V2 receptors in renal tubular cells in collecting duct, insertion of aquaporin-2
acts on V1 receptors at higher concentration - vasoconstriction (vasopressin)
121
when does the body release ADH?
- when serum osmolality increases (e.g. don't drink), release ADH & reabsorb water to bring osmolality down
- low blood volume/low BP (as sensed by baroreceptors)
122
how does cardiac failure cause hyponatremia (hypervolemic)
reduced CO --> reduced BP --> sensed by baroreceptors --> increased ADH --> increased water retention --> decreased [Na]
123
how does cirrhosis cause hyponatremia (hypervolemic)
increased NO --> vasodilation --> reduced BP --> sensed by baroreceptors --> increased ADH --> increased water retention --> decreased [Na]
124
how does hypothyroidism cause hyponatremia (euvolemic)
reduced cardiac contractility --> reduced BP --> sensed by baroreceptors --> increased ADH --> increased water retention --> less [Na]
125
how does adrenal insufficiency cause hyponatremia? (euvolemic)
low cortisol --> low BP --> more ADH --> more water --> less [Na]
126
do you give normal saline to someone with SIADH?
NO!
| You are adding more water to someone retaining water, causing hyponatremia to drop further. You will make them sicker.
127
how do you treat hyponatremia from SIADH?
fluid restriction, treat underlying cause
128
how do you treat someone with hyponatremia that is hypovolemic?
normal saline 0.9%
129
how do you treat someone with severe hyponatremia?
reduced GCS, at risk of seizures. Need urgent hypertonic saline (2 or 3%). You want to increase it slowly (no more than 8-10 mmol/L in 24 hours).
130
how do you treat someone with euvolemic hyponatremia?
fluid restriction, treat the cause
131
what is the most important risk in correcting hyponatremia?
must NOT be corrected by >8-10 mmol/L in 24 hours due to risk of osmotic demyelination (Central Pontine Myelionlysis)
132
what happens in central pontine myelionlysis (osmotic demyelination)?
quadriplegia, dysarthria, dysphagia, seizures, coma, death -- all 2-6 days after treatment
endothelial shrinkage --> disrupted BBB --> cytotoxic complements can penetrate BBB
133
if water restriction is insufficient, what drugs can be used to treat SIADH?
demeclocycline (causes ADH resistance, monitor U&Es)
| tolvaptan (V2 receptor antagonist)
134
what are the causes of hypernatremia?
```
loss of water:
GI Loss (diarrhea/vomiting) if not replacing with water, or because not enough ADH (e.g. diabetes insipidus)
```
135
how do you treat hypernatremia? (4 steps)
1) fluid replacement (NOT with normal saline)
- -> 5% dextrose
2) correct any ECF volume depletion (with 0.9% saline)
3) serial 4 hrly Na level checks
4) treat underlying cause
136
suppose a patient has significant GI losses and
a) are drinking water
b) are not drinking water
will they have hyponatremia or hypernatremia?
a) hypo
| b) hyper (not replacing GI losses)
137
someone comes into A&E unconscious, known diabetic. Cannot swallow. What are the steps of treatment? (3 steps)
1) IV Access
2) 50ml of 50% glucose or 100 mls of 20% glucose
3) if difficult to do any of the above, consider IM/SC 1mg glucagon
138
what are the 4 steps the body naturally does when glucose is running low and in what order?
1) reduce peripheral uptake of glucose
2) increase glycogenolysis
3) increase gluconeogenesis
4) increase lipolysis
139
name the oral hypoglycemic drugs that can be given for diabetes TMD2 (3 classes)
sulfonylureas
GLP-1 agents
meglitinides
140
name the syndrome that can occur when DM Type 2 is concurrent with Addisons and what is it?
polygladular autoimmune syndrome
| hypos common
141
what is c-peptide?
product of insulin cleavage (takes longer to clear in the blood system)
142
name some causes of hypoglycemia with low insulin, low C-peptide levels?
```
fating/starvation
critical illness
strenous exercise
hypopituitarism
liver failure
anorexia nervosa
(any appropriate response to hypoglycemia)
```
143
which metabolic disorders can cause neonatal hypoglycemia? what will insulin & C-peptide levels be?
suppressed insulin, suppressed C-peptide, low ketones -->
FAOD
GSD type 1
MCADD
Carnitine disorders
144
name that cause: neonatal hypoglycemia, raised fatty acids, normal/low ketones
```
Fatty acid defects
metabolic issues (eg MCADD)
```
145
name that cause: neonatal hypoglycemia, normal/low fatty acids, normal/low ketones
hyperinsulinism
| hypopituitarism
146
name that cause: neonatal hypoglycemia, with raised FFA, raised ketones.
glycogen storage issues
drug toxicitiy (if lactate high)
glucocorticoid deficiency
septicemia
147
what are the 3 causes of pancreatic islet cell hyperplasia?
infant of a diabetic mother
Beckwith Weidemann Syndrome
Nesidioblastosis
148
spot diagnosis: low glucose, high insulin, high C-peptide, having fits
endogenous insulin production if high c-peptide. Thus, insulinoma or sulphonylurea abuse.
149
spot diagnosis: decreased glucose, increased insulin, decreased c-peptide
factitious (extra external )insulin
150
spot diagnosis: decreased glucose (persistent despite glucose infusion), decreased insulin, decreased c-peptide, decreased FFA, ketones negative
non-islet cell tumor hypoglycemia (paraneoplastic syndrome from secretion of IGF2)
151
6 aspects of normal liver function:
```
intermediary metabolism
protein synthesis
xenobiotic metabolism
horomone metabolism
bile synthesis
reticulo-endothelial system
```
152
what 3 types of chemical modification occurs in the liver?
P450 enzyme system
acetylation/de-acetylation
redox
153
what 3 types of hormones are metabolised in the liver and how?
vitamin D - hydroxylation
steroid hormones - conjugated/excreted
peptide hormones - catabolised
154
what is the purpose of Kupffer cells in the liver?
clearance of infection/LPS
antigen presentation
immune modulation (cytokines)
155
what are the immune modulating cells of the liver?
Kupffer cells
156
what are the two parts of the liver that make up reticuloendothelial function?
Kupffer cells
| EPO
157
what 6 tests fall under LFTs?
```
ALT
AST
ALP
GGT
PT
AFP
```
158
what 4 LFT tests show serum markers of liver cell damage?
ALT, AST, ALP, GGT
159
what two LFT tests show marker of function?
albumin
| PT
160
when are ALT and AST raised?
when hepatocytes die -
| AST specifically in alcoholic liver disease, cirrhosis
161
when is GGT raised?
in chronic alcohol use; bile duct disease; hepatic metastasis
162
when is ALP raised?
markedly elevated if obstructive jaundice or bile duct damage, less elevated in viral hepatitis or alcoholic liver disease
163
when is albumin low?
low production, loss (gut, kidney), sepsis or '3rd spacing'
164
is unconjugated or conjugated bilirubin raised in pre-hepatic causes of jaundice?
pre-hepatic cause = hemolysis so, unconjugated raised
165
is unconjugated or conjugated bilirubin raised in hepatic causes of jaundice?
hepatic causes: genetic, hepatitis, drugs
| both unconjugated & conjugated are raised
166
is unconjugated or conjugated bilirubin raised in post-hepatic causes of jaundice?
post- hepatic causes are bile duct obstruction, drugs
| conjugated bilirubin is raised in post-hepatic
167
what dye tests are used to measure hepatic blood flow and excretory capacity of the liver?
indocyanine green
| bromsulphalein
168
what breath tests are used to measure reisdual functioning liver cell mass?
aminopyrine
| galactose (carbon 14)
169
what is the purpose of doing ALT/AST/GGT/ALP?
help to locate site/cause of inflammation or cell damage in liver
170
what is the purpose of albumin/PT tests?
represent the 'synthetic' function of liver, prognostically important in acute and chronic liver disease
171
List the six anterior pituitary hormones & what stimulates their release:
```
GH - controlled by GHRH
prolactin - controlled by TRH
TSH - controlled by TRH
LH/FSH - controlled by LHRH
ACTH - controlled by CRH
```
172
what will patients present with in pituitary failure?
galactorrhea/amenorrhea (in females)
| subtle/nothing often seen in males
173
when is a pituitary tumor termed to be macroadenoma?
>1cm
174
what complication of a large pituitary tumor should you watch out for?
bitemporal hemianopia
175
spot diagnosis: 30 year old with galactorrhea, never had sexual intercourse, prolactin 30,000
large tumor, prolactinoma
176
Pituitary Function testing:
LHRH + TRH + stress (hypoglycemia) administered --> then measure ACTH/GH, cortisol
should increase cortisol --> ACTH and GHRH --> GH
177
what is a 'Triple Test' with regards to pituitary?
hypoglycemia (must be <2.2mM glucose)
TRH
LHRH
should stimulate TSH, prolactin, ACTH, GH if no pituitary failures
178
If someone is in complete anterior pituitary failure - what order does replacements need to be? (5 steps)
1) hydrocortisone
2) thyroxine
3) estrogen
4) GH replacement
5) treat prolactinoma with dopamine agonist (bromocriptine or cabergoline)
179
what effects do non-functioning pituitary adenomas have?
press on stalk causing pituitary failure cause hyperprolactinemia
180
adrenal failure:
fludrocortisone, not hydrocortisone
181
what test can we use to confirm acromegaly?
glucose tolerance test (should suppress GH to zero) or IGF1
182
what is the best treatment for acromegaly?
octreoide or pituitary surgery
183
what does the zona fasciculata of the adrenal make?
cortisol
184
what does the zona glomerulosa make in the adrenal gland?
aldosterone
185
spot diagnosis: very high TSH with low free T4
primary hypothyroidism
186
spot diagnosis: high TSH, high free T4
TSH producing pituitary adenoma
187
what deficiency is suggested by hyponatremia, hyperkalemia?
deficiency of mineralocorticoid (aldosterone)
188
spot diagnosis: low sodium, high potassium, low glucose
adrenal failure --> Addison's disease
189
what is Schmidt's Syndrome?
Addison's disease + Primary Hypothyroidism
190
how do you test for Addison's disease?
short synacthen test (ACTH); measure cortisol and ACTH before and after injection. Check at 30 minutes, 60 minutes. If don't rise in cortisol, then positive
191
possible adrenal masses:
phaeochromocytoma (adrenaline secreting)
Conn's syndrome (aldosterone secreting)
Cushing's syndrome (cortisol secreting)
192
phaeochromocytoma treatments:
urgent - alpha blockers (phenoxybenzamine)
then add beta-blockers,
then long-term - surgery
193
spot diagnosis: hypertension, low potassium, raised aldosterone, suppressed renin
Conn's syndrome
194
in a hypertensive with low potassium, what do you need to think of?
aldosterone (raised) and renin (suppressed) via Conn's syndrome
195
spot diagnosis: hypertensive woman with bruising, sodium borderline high, potassium low, renin low, aldosterone low
Cushing's syndrome
196
what tests do you do for cushing's?
9 am cortisol (meant to be high)
12 am (midnight) cortisol (meant to be low)
dynamic test: dexamethasone suppression test
197
what are potential causes of cushing's syndrome? (4)
1) oral steroids treatment for something else
2) cushingoid tumor (ectopic ACTH, 5%)
3) pituitary dependent Cushing's disease (in 85% not on steroid)
4) adrenal adenoma (10%)
198
what is the normal result (non pathological) of dexamethasone suppression test?
should fall to undetectable levels
199
spot diagnosis: low dose dexamethasone does not suppress but high dose dexamethasone does suppress
pituitary dependent Cushing's disease (do pituitary MRI for microadenomas)
200
spot diagnosis: low dose dexamethasone does not suppress, high dose dexamethasone does not suppress
ectopic ACTH, or lung cancer (do CXR to look for an ectopic source)
201
which of the following commonly presents with depression?
a) hyperkalemia
b) hypokalemia
c) hypercalcemia
d) hypocalcemia
e) uraemia
c) hypercalcemia
202
what does hypocalcemia?
irritability, fits, tetany
203
spot diagnosis: abdominal pains and frank blood
renal stones
204
what are the two reasons why enzyme levels may increase?
cell necrosis/damage & leaky membranes
205
where is alk phos (ALP) found?
in high concentrations in liver, bone, intestine, placenta
206
causes of raised ALP (two bone, two liver)
bone: pagets, osteomalacia
liver: cholestasis, cirrhosis
207
what are the 3 forms of CK (creatine kinase) and where are they found?
CK-MM: skeletal muscles
CK-MB: cardiac muscles (1&2)
CK-BB: brain (minimal even in severe brain damage)
208
causes of raised CK (creatine kinase)?
```
Muscle damage due to any cause
Myopthy e.g. Duchenne muscular dystrophy (>10xULN)
Myocardial Infarction (>10xULN)
Severe exercise (5xULN)
Physiological – Afro-Caribbean (<5xULN)
Polypharmacy
High-dose statin
```
209
what are the 3 cardiac markers of MI?
CK-MB
Cardiac Troponin
Myoglobin
210
what is the relation between PTH and calcium?
inverse - if calcium goes up, PTH is no longer produced
211
spot diagnosis: high calcium, 'normal' PTH, many fractures
primary hypoparathyroidism
| inappropriately normal PTH
212
spot diagnosis: high calcium, low PTH, many fractures
cancer (mets)
213
what are 40-60% of renal stones composed of?
calcium oxalate or phosphate (will be radioopaque)
214
what are staghorn renal stones made of?
struvite (magnesium ammonium phosphate)
215
emergency treatment for hypercalcemia?
fluids (0.9% saline) -4L in 24 hours via IV access
induce diuresis with furosemide
if patient has known cancer --> IV pamidronate 30-60mg
216
non-urgent treatment for hypercalcemia?
keep hydrated, avoid thiazides. Use surgery (parathyroidectomy)
217
spot diagnosis: BHL on CXR, suppressed PTH, hypercalcemia
sarcoidosis
| treatment - high dose steroids
218
how does sarcoidosis cause high calcium?
unregulated macrophages in the lungs producing 1-alpha hydroxylase and activating vitamin D. This causes more absorption of the calcium.
219
name 4 causes of pre-renal AKI
Hypotension
Oedematous states
Selective renal ischaemia
Drugs affecting glomerular blood flow
220
how do we classify` AKI?
pre-renal
renal
post-renal
221
T or F: Pre-Renal AKI is not associated with structural renal damage and responds immediately to restoration of circulating volume
T
222
what is the hallmark of post-renal AKI?
obstruction to flow in the kidneys
223
list 3 possible causes of post-renal AKI:
```
Ureteric obstruction (bilateral)
Prostatic / Urethral obstruction
Blocked urinary catheter
```
224
T or F: Immediate relief of obstruction (post- renal AKI) restores GFR fully, with no structural damage
T
225
what is the hallmark of intrinsically renal AKI?
abnormality of any part of nephron
226
list 4 possible causes of renal AKI:
Vascular Disease eg vasculitis
Glomerular Disease eg glomerulonephritis
Tubular Disease eg ATN
Interstitial Disease eg analgesic nephropathy
227
list 3 causes of direct tubular injury in kidneys:
drugs /contrast - exogenous toxins
myoglobin, Igs - endogenous toxins
ischemic
228
what two chemical measures do we have for the severity of an AKI?
creatinine & urine output
229
what is a normal level of GFR?
>90
230
what are 6 causes of CKD?
- Diabetes
- Atherosclerotic renal disease
- Hypertension
- Chronic Glomerulonephritis
- Infective or obstructive uropathy
- Polycystic kidney disease
231
T or F: Whereas AKI is irreversible, CKD is reversible
F (opposite)
232
list 5 consequences of CKD:
1]Progressive failure of homeostatic function
- Metabolic Acidosis (treat w/oral Na bicarb)
-Hyperkalaemia (ECG Changes - wide QRS with peaked T wave)
2]Progressive failure of hormonal function
-Anaemia (Normochromic, normocytic )
-Renal Bone Disease (hyperparathyroidism)
3]Cardiovascular disease
-Vascular calcification
-Uraemic cardiomyopathy (LV hypertrophy, dilatation, dysfunction)
233
what test confirms Diabetes Mellitus Type 2?
Fasting plasma glucose > 7.0mM
2 hour GTT plasma glucose > 11.1 mM
Hba1c > 6.5% (currently in WHO discussions)
234
3 causes of metabolic alkalosis:
sodium bicarbonate ingestion
loss of H + (vomiting)
hypokalemia
235
what is the relationship between hypokalemia and alkalosis?
hypokalemia & alkalosis cause each other. the process of not having enough K+ into cells means that H+ goes into cells - thus raising the pH and causing an alkalosis. the presence of H+ brings K+ into cells, thus causing a hypokalemia
236
what is the relationship between sodium and potassium in the collecting duct? (think hypokalemia... hyponatremia...)
Two separate processes.
Sodium is controlled in the distal collecting duct of the kidney by aldosterone. When aldosterone is increased, SODIUM absorption is increased as is H2O (via ADH). ADH levels and water then determine sodium concentration.
i.e. by the same pathway, SIADH would lead to more water absorption and decreased sodium concentration
Meanwhile, potassium is controlled by the osmotic and electrochemical gradients of the DCT. Thus when aldosterone brings sodium out, the lumen is more negative and potassium moves from ICF to ECF in the lumen to make it more positive. Potassium fixes the gradient. Osmotic diuresis also has an effect on the potassium - as glucose will take out H20 and Potassium with it. .
237
what is the most common cause of primary hypercholesterolaemia?
familial hypercholesterolaemia, due to loss of function mutations of the LDL receptor and apoB-100 genes or gain of function mutations of the PCSK9 gene
238
how does one have primary HYPOcholesterolaemia?
Primary hypolipoproteinaemia (hypolipidaemia) is always of genetic origin and includes abetalipoproteinaemia, due to recessively inherited mutations of microsomal triglyceride transport protein (MTP); familial (homo or heterozygous inheritance of apoB gene mutations), or Tangier disease
239
where is cholesterol (i.e. lipid) transport in the plasma volume?
- LDL carries 70% of cholesterol
| - HLDL/VLDL carry about half of the remainder each
240
in comparison, where is the most of the triglyceride transport in plasma volume?
- VLDL alone carries about 55% of the body's triglycerides
| - LDL carries about 30%
241
what is the 'life cycle' of the triglyceride and cholesterol in the blood?
-bile salts and cholesterol picked up from bloodstream by chylomicrons --> move remnant FFA to liver --> the liver converts VLDL into LPL, IDA, FFA, adipose tissue. The adipose tissue can be brought back to the liver with FFA/Albumin combined
242
when do tendon xanthomas present?
hypercholesteremia
243
how does H+ come out into the kidneys?
- DCT
- when Na + comes out, exchange for H+
- bicarbonate regenerated and comes out into the body
- Bicarbonate reabsorption also in the proximal tubule
244
how is CO2 regulated in the body?
- CO2 is produced in protein, carb, and fat metabolism and excreted from the lungs
- CO2 excretion controlled by chemoreceptors in the hypothalamic respiratory centre
- CO2 transported in the blood with water: CO2 + H20 --> H + HCO3
- the bicarbonate is used for balance, the H+ combines with hemoglobin
245
what happens in the body in metabolic acidosis?
- increased H+ (decreased pH) with decreased bicarbonate
- either because we've made too much H+, are not excreting enough H+ or lost too much bicarbonate
- -> DKA (too much), Rental Tubular Acidosis (can't excrete enough), intestinal loss (losing bicarb)
- this stimulates the respiratory center to compensate (as seen by fall in PCO2 - rise in RR)
246
what is acronym ROME referring to in acid-base balance?
Respiratory Opposite
Metabolic Equal
looking at PCO2 & pH and the direction out of normal values that it lies (eg metabolic acidosis - pH dec, and PCO2 dec)
247
what happens in the body in respiratory acidosis?
Increased CO2 --> increased H+ --> decreased pH, increased HCO3
Causes: poor lung perfusion, poor air intake, impaired gas exchange (ie. too much CO2 kept in); eg- pneumonia, copd
Metabolic compensation: increased renal excretion of H+ combined with generation of bicarbonate (leading to inc. bicarb and CO2 levels remaining) --> pushes from 'acute' to 'chronic' resp acidosis
248
what happens in the body in metabolic alkalosis?
*decreased H+ --> increased pH; increased bicarb.
Causes - either ingesting too much biarcbonate; losing too much H+ (GI loss) or decreased K+ (as K+ ECF means H+ ICF for electrochemical gradient)
Compensated --> respiratory center inhibited so rise in pCO2
249
which acid-base imbalance is hypokalemia associated with?
metabolic alkalosis:
A low K+ concentration outside the cell will lead to the raising of the pH of the fluid outside the cell because of H+ ions from outside the cell being exchanged for K+ ions from inside the cell. (lower H+ = higher pH)
250
what happens in the body in respiratory alkalosis?
-happens when the body is getting rid of CO2 too quickly, so that shifts the balance of the H+ + HCO3 - H2C03 CO2 + H2O so that H+ and HCO3- must also decrease
Causes: hyperventilation (eg panic attack)
Metabolic compensation:
If prolonged resp. alkalosis this leads to decreased renal excretion of H+ and less bicarbonate generation (pCO2 low, bicarb low)
251
define positive and negative predictive value, i.e. PPV and NPV:
PPV - True positive / Total positive
| NPV - true negative/ total negative
252
name some tests on Guthrie card for newborns -
```
PKU from 1969
Congenital hypothyroidism added 1970
Sickle cell disease added 2006
Cystic fibrosis
Homocystinuria
Maple Syrup Urine Disease
MCADD
+ urea cycle, AA, fatty acid oxidation, organic aciduria disorders
```
253
what sort of presentation would make you wonder if somebody has a uric cycle disorder?
RED FLAGS
- vomiting w/o diarrhea
- respiratory alkalosis
- hyperammonemia
- neuro: encephalopathy, coma, confused
- avoidance/change in diet causing these effects
254
how would you treat someone presenting with a uric acid cycle disorder?
- means that they are unable to deal with ammonia in the body, which is toxic when it builds up
- treat by reducing ammonia produced and removing the ammonia present
255
what is the inheritance & pathophysio of uric acid cycle disorders?
- usually Auto Recessive (except OTC def which is x-linked)
- 7 possible defects
- all lead to hyperammonemia
256
when would you suspect someone of having an organic aciduria?
Adult/Child:
- Hyperammonaemia with metabolic acidosis and high anion gap
- cheesy/sweaty smell
- recurrent episodes of ketoacidotic coma, Reye syndrome
Neonate:
- abnormal smell (cheesy/sweaty)
- lethargy
- feeding problems
- hypocalcemia
- neutropenia/pancytopenia
- truncal hypotonia / limb hypertonia, myoclonic jerks
257
what is Reye syndrome?
Presents with vomiting, lethargy, increasing confusion, seizures, decerebration, respiratory arrest
Triggered by: e.g. salicylates, antiemetics, valproate
258
how would we test for Reye syndrome?
```
Plasma/blood ammonia
Plasma / urine amino acid
Urine organic acids
Plasma/blood glucose and lactate
Blood spot carnitine profile - will stay abnormal in remission
```
259
when do we suspect that somebody may be presenting with a fatty acid oxidation abnormality (eg MCADD)?
Hypoketotic hypoglycaemia
Hepatomegaly
Cardiomyopathy
(Bloods will show abnormal blood ketones, acylcarnitine profile, and urine organic acids)
260
what is the most common carbohydrate metabolism disorder?
galactose-1-phoshate uridyl transferase (Gal-1-PUT) is the most severe and the most common. It will cause liver & kidney disease
261
how do carbohydrate metabolism disorders present?
-D&V
-conjugated hyperbilirubinemia
-hepatomegaly
-hypoglycemia
-sepsis
Almost always in neonate (w/o treatment won't become adult). bilaterial cateracts as kids from carb abnormal metabolism SE
262
Besides digesting and metabolizing carbohydrates, we also need to store them appropriately - how would someone with a glycogen storage disorder present?
```
Hypoglycaemia
Lactic acidosis
Neutropenia
Hepatomegaly
Nephromegaly
```
263
what is MELAS and how does it present?
MELAS ('mitochondrial encephalopathy, lactic acids and stroke-like episodes')
- mitochondrial disorder
- usually presents in ages 5-15
- lactic acid in blood
- stroke-like episodes
- mito. encephalopathy
264
what is Kearns-Sayre disorder and how does it present?
-mitochondrial disorder
-usually presents over the age of 15
Presents with: Chronic progressive external ophthalmoplegia, retinopathy, deafness, ataxia
265
what tests do you want to run when you suspect a mitochondrial disorder?
- Elevated lactate (alanine) – after periods of fasting, before and after meals
- CSF protein (raised in Kearns-Sayre syndrome)
- CK
- Muscle biopsy
266
When we store glycogen and then utilize it later, we need to glycosylate. How might someone with a glycosylation disorder present?
-Multisystem disorders
-associated with cardiomyopathy, osteopenia, hepatomegaly
E.g. CDG type 1a - abnormal subcutaneous adipose tissue distribution with fat pads and nipple retraction.
Check: blood serum transferrin glycoforms
267
If a perioxosomal disorder is not detected at birth, how might neonate present?
peroxisome - Metabolism of very long chain fatty acids and biosynthesis of complex phospholipids
* severe muscular hypotonia
* seizures
* hepatic dysfunction (including hyperbilirubinaemia
* retinopathy often with sensorineural deafness
* mental deficiency
X-ray: Bony changes involve a large fontanel which late, osteopenia of long bones, and often calcified stippling
Profile: very long chain fatty acids in neonate/child's blood
268
Lysosomal storage diseases present in a very severe fashion at a very young age. What would the infant be suffering with?
*organomagaly (connective tissue, solid organs, cartilage, bone and nervous tissue)
*consequent dysmorphia and regression
May be detected on urine - mucopolysaccharides / oligosaccharides
Treatment requires bone marrow transplant.
269
what is the 'classic' presentation of mitochondrial disorders?
chronic muscle weakness with hyperlactataemia.
270
at what age do glycogen storage disorders usually present?
3-6 months
271
what are common disorders seen in low birthwright neonates?
- Intraventricular haemorrhage
- Patent ductus arteriosus
- Central pontine myelinolysis
- Bronchopulmonary dysplasia (RDS)
- necrotising enterocolitis
272
in neonates presenting with jaundice, what are we most worried about?
Kernicterus may develop if total bilirubin exceeds 340 mol/l in the term neonate; this
273
what happens in neonates with hypercalcemia?
High foetal ionised calcium concentration causes suppression of the foetal parathyroid. Transient post-natal hypocalcaemia is the norm.
274
what can cause hypernatremia in neonate?
beyond 2 weeks of age - usually dehydration
| before 2 weeks of age -often due to drugs, skin loss of ECF, RR, not having as developed kidneys...
275
what can cause hyponatremia in the neonate?
CAH - congenital adrenal hyperplasia. Increased levels of 17-OH-progesterone and a blockage from creating aldosterone/cortisol....
- hyponatremia
- hyperkalemia
- marked dehydration
- hypoglycemia
- females have ambiguous genitalia from birth
276
what can cause neonatal jaundice in under 24 hours of age?
Always pathological -
Haemolytic disease (ABO, rhesus etc)
G-6-PD deficiency
Crigler-Najjar syndrome
277
what are some causes of conjugated hyperbilirubinemia, presenting with prolonged neonatal jaundice?
```
hepatitis
sepsis
inherited metabolic disorders
biliary atresia
choledocal cyst
polysplenia,
ascending cholangitis in TPN
```
278
what is the biochemistry in osteopenia of prematurity in neonates?
Calcium: within reference range
Phosphate <1mmol/L
Alk phos >1200 U/l ( 10 x adult ULN)
Vitamin D rarely measured in neonate
279
how does the hypothalamic-THYROID axis work?
*TSH controls iodine uptake and conversion by thyroid to iodide. This iodinates tyrosine which joins with itself to form thyroxine - T3/T4
- hypothalamus releases TRH to stimulate pituitary to release TSH which stimulates the above in thyroid. Thyroid releases the T3/T4 ... converted by type 1 monodeiodinase which makes it tri-iodothyronine and causes effects
* The T4 provides negative feedback to TSH from pituitary which provides negative feedback to hypothalamus
280
what is the biochemistry in hypothyroidism?
Since T4 is not eliciting negative feedback effect on pituitary - TSH is high.
T4/T3 is low - not producing enough in hypothyroidism.
Can use TRH stimulating test to distinguish if cause is pituitary or hypothalamus. If TRH stimulating test leads to increase in TSH - problem is in the hypothalamus not producing TRH. If it does NOT lead to increase - TSH cannot be stimulated in pituitary... so pituitary is the problem
281
what happens to thyroid biochemistry when somebody is severely ill?
'sick euthyroid'
TRH: normal
TSH: high-normal (trying to stimulate thyroid), later on will decrease
T3/T4: low
282
what side effects do we worry about if somebody with previous hyperthyroidism is placed on PTU or carbimazole?
Rare SE of agranulocytosis (<1%). Warn to stop if sore throat or fever and check FBC. Routine tests of no value
283
what are the two types of differentiated thyroid carcinomas and how do we investigate thyroid cancer?
Papillary thyroid cancer
Follicular thyroid cancer
Give thyroglobulin - ought to suppress TSH. If continues to express TSH -- must be malignant cells
284
who gets medullary carcinoma of the thyroid and what investigative test can help determine it?
MTC can be sporadic, familial, associated with MEN
- C cells of thyroid
- CEA antigen test
285
what is lesch-nyan syndrome?
a complete deficiency of HGPRT enzyme involved in purine catabolism.
While babies present as quite normal at birth, they quickly develop to have developmental delay apparent by 6 months and choreiform movements by 1 year. They have mental retardation in growth and uncontrollable self-mutilation urges in childhood/adolescence. Bloods - Hyperuricaemia
286
what is the pathophysiology of gout?
* Monosodium urate crystals build up into exquisitely acutely painful tophi on joint (red,hot, swollen)
* post-pubertal males, post-menopausal females
* Usually 'big toe joint' (1st MTP)
* Can be acute (Podagra) or chronic (Tophaceous)
287
the way you manage an acute gout flare-up is different from chronic condition. What is the management of acute gout?
-NSAIDs
-Colchicine
-Glucocorticoids
Do NOT attempt to modify plasma urate concentration
288
what is the management of chronic gout (between flare ups)
allopurinol (unless on Azathioprine!)
| hydration/dietary changes
289
how do we tell the difference between gout and pseudogout?
gout- Monosodium urate crystals; negatively birefringent
| pseudogout- calcium pyrophosphate dihydrate crystals; positively birefringent ( along axis)
290
what is pseudogout and who gets it?
- osteoarthritis patients
- self limiting in 1-3 weeks (no need for chronic allopurinol, etc)
- calcium pyrophosphate crystals (not urate)
