MEH conditions Flashcards
(204 cards)
1
Q
What is the effect of G6DP deficiency?
A
- Reduced activity of the enzyme so low level of NADPH. NADPH is required for reduction of oxidised glutathione back to active reduced form
- Reduced glutathione is needed for oxidative damage protection
2
Q
Why are red blood cells particularly affected by G6DPH deficiency?
A
The only source of NADPH they have is from the G6DP reaction. This results in haemoglobin cross linkage due to oxidative damage and formation of Heinz bodies.
3
Q
What is the cause of Galactosaemia?
A
Lack of Galactokinase enzyme and galactose-1-phosphate Uridyl transferase enzyme (more common).
4
Q
What is galactosaemia?
A
- Lack of galactokinase results in accumulation of galactose
- Lack of Galactose-1-phosphate uridyl transferase enzyme and UDP epimerise enzyme results in increase in Glalactose and Galactose-1-Phosphate.
- Accumulation of galactose results in aldose reductase reducing it to galactitol and depleting NADPH.
5
Q
What is the effect of galactosaemia?
A
- In the eye it causes cataracts due to lens structure damage via cross linking of proteins by disulphide bonds. There also could be non enzymatic glycosylation of the lens protein due to high lactose which contribute to cataracts
- There could be increased intra-occular pressure applied on the eye due to accumulation of galactose and galacticol therefore causes glaucoma
- Damage to liver, brain, kidney due to galactose 1 phosphate accumulation
6
Q
What cause essential fructosuria?
A
Fructose kinase missing
7
Q
What causes fructose intolerance?
A
Aldolase missing. The fructose 1 phosphate accumulates in the liver leading to liver damage
8
Q
What smell is present on the breath of untreated type 1 diabetic patients?
A
Smell of acetone.(nail polish remover)
9
Q
What is the cause of ketoacidosis?
A
High concentrations of acetoacetate and beta hydroxybutyrate.
10
Q
What is the mechanism of action of Statin?
A
They inhibit HMG-CoA reductase so less cholesterol is synthesised.
11
Q
What is the effect of excessive alcohol consumption on the liver?
A
-Decrease in NAD+/NADH ratio and the increased availability of acetyl CoA lead to increased synthesis of fatty acids and ketone bodies.
-Newly synthesised fatty acids are converted to triacylglycerols
-Lack of lipoprotein synthesis causes a fatty liver
In some cases ketone body production is sufficient to cause ketoacidosis
12
Q
What is used as an adjunct in treatment for alcohol dependance?
A
Disulfiram. Causes accumulation in acetaldehyde and causes a hangover.
13
Q
What can damage to hepatocytes lead to?
A
- Hyperbilirubinaemia due to reduction in the liver capacity to take up conjugate bilirubin which may produce jaundice
- Oedema due to low serum albumin
- Decreased in capacity to produce urea so this leads to hyperammonaemia and increased level of glutamine
- Decreased amounts of clotting factors lead to increase in blood clotting time
14
Q
What is chronic pancreatitis?
A
Inflammation of the pancreas due to chronic heavy alcohol consumption. Symptoms are
- constant pain in the upper abdomen that radiate to the back
- weight loss due to malabsorption causes by insufficient enzyme production
- if the beta pancreatic cells are damaged, lack of insulin leads to hypoglycaemia and glycosuria
15
Q
What is produced when a toxic dose of paracetamol is ingested?
A
NAPQI which is a strong oxidising agent and is conjugated with glutathione depleting its levels. This causes oxidative stress
16
Q
What the treatment for paracetamol overdose?
A
Acetylcysteine (within 8 hours) to replenish the glutathione levels so liver can safely metabolise the NAPQI. Beyond 8 hours, death as a result of liver failure may be inevitable
17
Q
What is the cause and symptoms of phenylketonuria?
A
Defective phenylalanine hydroxylase enzyme which so phenylalanine accumulates in tissues and blood. It is metabolised in other pathways which causes the production of phenylpyruvate which is excreted in the urine.
If untreated results in inhibition of brain development due to inhibitor of pyruvate uptake into mitochondria by phenylpyruvate.
18
Q
How is phenylketonuria diagnosed?
A
Phenylketone detected in the urine
Measurement of the blood phenylalanine concetration
At birth the Heel prick test
19
Q
What is homocystinuria?
A
Rare autosomal recessive defect in methionine metabolism in which the 1 is caused by a deficiency in cystathionine B-synthase (CBS) enzyme. Levels of homocysteine increase in blood and some of this is converted to methionine. Increase in plasma levels of homocysteine can cause disorders of connective tissue, muscle, CNS and cardiovascular system. Detected by high levels of methionine and homocysteine in plasma and homocysteine in urine.
20
Q
How does homocystunuria present in children and why is this important?
A
Similar symptoms to marfan’s syndrome so can be misdiagnosed. The fibrillin-1 protein structure is affected.
21
Q
What is refeeding syndrome?
A
When nutritional support is given to severely malnourished patient, due to the enzyme in the urea cycle not being induced to handle the amount of nitrogen being introduced, it can result in a toxic ammonia concentration which can cause death. Therefore it is important to gradually raise to their full needs over a week.
22
Q
What does defect in one of the enzyme in the urea cycle result in?
A
-Hyperammonaemia
-Accumulation and/or excretion of particular urea cycle intermediate
Symptoms
-Irrittability
-Vomiting
-Lethargy
-Mental retardation
-Seizures
-Coma
-Death
23
Q
What is the treatment for defect in enzyme in the urea cycle?
A
Low protein diets or a diet in which the keto acids of the essential amino acids are used to replace the amino acids themselves which used NH4+ so lowers it concentration
24
Q
What is Von gierke’s disease?
A
Glucose-6-phosphatase deficiency
25
What is McArdle disease?
Muscle glycogen phosphorylase deficiency
26
What is the effect of defect of enzymes in the glycogen cycle?
```
Increased or decreased amounts of glycogen which may cause:
-Fasting Hypoglycaemia
-Tissue damage if excessive storage
-Poor exercise tolerance
-Glycogen structure may be abnormal
Usually liver and/or muscle affected
```
27
What can disorder in lipoprotein metabolism lead to?
Atherosclerosis and Coronary artery disease
28
What causes unstable lipoproteins of abnormal structure?
Deficiency in the LCAT enzyme. Less conversion of cholesterol to cholesterol ester using fatty acid derived from lecithin. Failure in the lipid transport process.
29
Why are LDL particles more likely to lead to formation of atherosclerotic plaques?
Longer half life so therefore increased chance of oxidative damage
30
What is familial hypercholesterolaemia?
Absence (Homozygous) or deficiency (heterozygous) of functional LDL receptors. The condition is characterised by elevated levels of LDL and cholesterol in plasma. Extensive atherosclerosis in homozygous sufferers early in life and later in life for heterozygous.
31
What is the cause of type 1 hyperlipoproteinaemia?
Caused by defective lipoprotein lipase. Chylomicrons in fasting plasma.
32
What is the cause of type 2a hyperlipoproteinaemia?
Caused by defective LDL receptor.
33
Which type of hyperlipoproteinaemia are linked with coronary heart disease?
Type 2a, 2b, 3, 4, 5
34
What is the cause of hyperlipoproteinaemia 3?
Defective apoprotein E. Raised IDL and chylomicron remnants.
35
What is the cause of hyperlipoproteinaemia 5?
Raised chylomicrons and VLDL in fasting plasma.
36
What are the clinical sign of hypercholesterolaemia?
- Xanthelasma
- Tendon xanthoma
- Corneal Arcus
37
What is the result of a splenectomy?
- Increased risk of infection by encapsulated bacteria
| - Increased risk of sepsis
38
What can cause hereditary spherocytosis?
Gene mutations in membrane associated proteins. (ankyrin, band 3, protein 4.2, spectrin)
39
What is iron deficiency ?
It is a symptom and not a diagnosis. Clinicians must treat the underlying cause which can be:
- excessive bleeding
- pregnancy
- insufficient intake or poor absorption
40
What is hereditary hemochromatosis?
An autosomal recessive disorder characterised by excessive absorption of dietary iron. Iron accumulates in tissues and organs disrupting their normal function as there is no system for iron secretion. Defect is in HFE gene which normally binds to transferrin receptor to reduce its affinity for iron-bound transferrin.
41
What is the presentation in a patient with hereditary hemochromatosis?
- Cirrhosis
- Adrenal insufficiency
- Heart failure
- Arthritis
- Diabetes
42
What is the treatment for hereditary hemochrombtosis?
Therapeutic phlebotomy to remove excess iron
43
What are the symptoms of acute onset anaemia?
- Fatigue
- Dyspnoea
- Palpitations
- Headache
- Angina and intermittent claudication in older patients
Clinical signs are
- Pallor
- Tachycardia
- Systolic murmur
44
Why might anaemia develop?
- Abnormal erythropoiesis (chemotherapy, radiating parvovirus, autoimmunity, chronic kidney disease)
- Abnormal haemoglobin synthesis (iron deficiency)
- Chronic disease (macrophages reduce RBC lifespan, IL-6 increase production of hepcidin)
- Globin gene mutation (Thalassaemia, sickle cell anaemia)
- Deficiencies in building blocks for DNA synthesis (folate, Vitamin B12)
- Deficiency in red cell metabolism (G6DPH deficiency, Pyruvate kinase defciency)
45
What are myeloproliferative neoplasms?
A group of diseases of the bone marrow in which excess cells are produced
46
What is the common molecular pathogenesis of myeloproliferative neoplasms?
Mutation of the gene coding for the tyrosine kinase Janus Kinase 2(JAK2)
47
What is thrombocythaemia?
Excess production of platelets by megakaryocytes
48
What is polycythaemia vera and its clinical features?
Characterised by overproduction of red blood cells.
Clinical features are
- Thrombosis
- Haemorrhage
- Burning pain in the hands and feet
- Pruritis
- Splenic discomfort, splenomegaly
- Gout
- Arthritis
49
What is myelofibrosis?
Characterised by replacement of the haematopoietic tissue by connective tissue leading to impairment of the generation of all blood cells.
50
What is the treatment of polycythaemia vera?
- Phlebotomy to maintain haematocrit below 45%
| - Aspirin is due to its anti-platelet effects may be prescribed unless contraindicated
51
What are the causes of polycythaemia?
- Increase in number of erythrocytes
| - Decrease in the plasma volume
52
What is the cause of acromegaly?
-Excess growth hormone secretion
53
What are the symptoms of acromegaly in an adult?
Gradual change in features over years
- Broad nose
- Coarse facial features
- Thick lips
- Prominent supraorbital ridge
- Enlargement of hands and feet
- Greasy skin with excessive sweating
- Deepening of the voice
54
What are the long term complications of acromegaly?
- Premature cardiovascular death
- Increased risk of colonic tumours
- Increased risk of thyroid cancer
- Hypertension and diabetes mellitus
55
What does excessive secretion of growth hormone in childhood lead to?
Gigantism
56
What is the test for excessive growth hormone secretion?
-Oral glucose tolerance test with GH response
-Failure to suppress GH
-Elevated IGF-1 level
-
57
What are 3 types of treatment for patient with acromegaly?
- Surgery to remove adenoma
- Radiation therapy
- Drug therapy (Pegvisomant, Carbegoline)
58
What are the structure surrounding the pituitary gland?
| you don't to remember according to lecturer but appreciate the effect of the tumour
Optic chasm(vision) - Superior
Oculomotor nerve and trochlear nerve (eye movement) - Lateral
Ophthalmic nerve and Maxillary nerve (Pain) - Medial
Internal carotid artery (blood supply) and Abducens nerve (lateral eye movement) - twist around it
59
What is the effect of growth of the tumour in the pituitary?
- Visual field loss
- Double vision and pain
- Eye compressive problems
60
What is the cause of hypopituitarism?
```
Commonly as a result of a pituitary adenoma
Rarer causes are:
-Radiation therapy
-Inflammatory disease
-Head injury
```
61
What is the deficiency of all anterior pituitary hormones called? Which hormones are affected first?
Panhypopituitarism
- GH
- LH/FSH
62
How is deficiency in growth hormone tested?
-Check response to hypoglycaemic stress
Growth hormone goes up in hypoglycaemia
63
How is an excess in GH tested?
-Suppress with glucose load
Growth hormone should decrease
64
What the indications of Gonadotropin deficiency?
- Lack of libido
- Infertility
- Oligomenorrhea or Amenorrhea in women of reproductive age
- Impotence in men
65
What is the classical change in appearance for Cushing disease?
- Round pink face (moon shaped)
- Abdominal obesity
- Skinny and weak arms and legs
- Thin skin and easy bruising
- Red/Purple stretch marks on abdomen
- High blood pressure
- Hyperglycaemia
- Osteoporosis
- Buffalo hump
66
What is the cause of diabetes insipidus?
Lack of vasopressin(ADH) so aqua porin channels are not opened so water isn't reabsorbed so increased urine.
Can be cranial (pituitary) or nephrogenic (kidney)
67
What are the consequence of untreated Diabetes insipidus?
- Severe dehydration
| - Very high sodium levels - reduced consciousness, coma and death
68
What is a prolactinoma?
Prolactin secreting tumour . The larger the tumour the higher the prolactin
69
What does hyperprolactinaemia in women cause?
- Menstrual disturbance
- Fertility problems
- Galactorrhea
- Hard breast tissue
70
What does hyperprolactinaemia in men cause?
- Usually presented later due to lack of periods
- Usually larger tumour
- Symptoms of low testosterone are not specific (Loss of sex drive, erectile dysfunction)
- May present with mass symptoms such as visual loss
71
Why is hypogonadism caused by the hyperprolactinaemia?
Higher level of dopamine (PIH) in the hypothalamus which inhibits GnRH secretion from the hypothalamus therefore FSH and LH secretion from anterior pituitary.
72
What is the treatment for prolactinoma?
Drugs such as Cabergoline and Bromocriptine. Not treated with surgery.
73
What are the causes of hyperprolactinaemia?
- Pregnancy
- Suckling
- Stress
- Exercise
- Antipsychotics
- Antidepressants
74
What situation of hyperprolactinaemia requires surgery?
Rare case where the prolactin increases due to disinhibition by dopamine as a result of a pituitary tumour blocking the secretion of dopamine. This may also inactivate ACTH or LH/FSH
75
What is marasmus?
A type of protein energy malnutrition common in children under 5.
76
What are the indications of marasmus?
- Emaciated with obvious signs of muscle wasting
- Loss of body fat with no oedema
- Hair is thin and dry.
- Diarrhoea is common
- Anaemia may be present
77
What is kwashiorkor?
A condition commonly seen in children who have a diet with low protein content and some carbohydrates. Typically with occurs in young children
78
How does kwashiorkor result in oedema?
There is insufficient amino acid for the liver to make a normal level of blood proteins such as albumin so the plasma oncotic pressure drops increasing net flow of fluid out of the vessel into the interstitium.
79
What are the signs of kwashiorkor?
- Apathetic
- Lethargic
- Anorexic
- Generalised oedema
- Abdomen distended due to hepatomegaly or ascites
80
What are the presentations of Type 1 diabetes?
Symptoms
- Polyuria : excess urine production. Loss of isosmotic reabsorption at the end of the proximal nephron so extra glucose remain in the tubule which means less water is also reabsorbed into blood so excess urine.
- Polydipsia : due to excess water loss
- Weight loss : fat and protein metabolism
Patient
- Usually young
- Presence of ketones
- Elevated venous plasma glucose
81
How can type 1 diabetes be diagnosed?
-Measured by plasma glucose levels. It is elevated due to lack of glucose.
82
What can type 1 diabetes cause if not dealt with urgently?
Diabetic ketoacidosis which is a life threatening crisis
83
What is glucosuria?
Glucose in the urine. Result of diabetes
84
What are the presentations of ketoacidosis?
- Prostration
- Hyperventilation
- Nausea
- Vomiting
- Dehydration
- Abdominal pain
85
What is it important to test for in a diabetic patient?
Ketones in the urine to assess diabetes control
86
What is the presentation of type 2 diabetes in a patient ?
- Polyuria : excess urine production. Loss of isosmotic reabsorption at the end of the proximal nephron so extra glucose remain in the tubule which means less water is also reabsorbed into blood so excess urine.
- Thirst : due to excess water loss
- Weight loss : fat and protein metabolism
- Lack of energy
- Persistent infections
- Particularly thrush infections of genitalia
- Foot infections
- Slow healing minor skin damage
- Visual problems
87
How can type 1 diabetes be cured?
It cannot. It has to be managed for the rest of the patients life with insulin injections. Increased dose with infections or trauma. This is done along an appropriate diet and exercise.
88
How can type 2 diabetes be managed?
- Managed by diet or oral hypoglycaemic drugs such as sulphonylureas that increase insulin release from the remain B-cells and reduce insulin resistance and particularly the suphonylurea called metformin that reaches gluconeogenesis
- Done alongside exercise and diet
89
What are the metabolic consequences of hyperglycaemia?
- Uptake of glucose into cells of tissues such as peripheral nerves, eye, kidney is determined by extracellular glucose concentration and not insulin dependant
- In hyperglycaemia, the intracellular concentration of glucose in these tissues increased. Glucose is metabolised via the aldose reductase enzyme to sorbitol
- Reaction depletes cellular NADPH and leads to increased disulphide bond formation in cellular proteins altering their structure and function.
- Accumulation of sorbitol causes osmotic damage to cells
90
How does persistent hyperglycaemia affect plasma proteins?
They undergo glycation that leads to disturbances in the proteins function.
91
What is the percentage of glycated haemoglobin a good indicator of?
Percentage of Glycated haemoglobin is a good indicator of how effective blood glucose control has been.
92
What does having over 10% of haemoglobin glycated indicate in a diabetic?
Poor controlled diabetes
93
What are the macroscopic complications of long term diabetes?
- Increased risk of stroke
- Increased risk of myocardial infarction
- Poor circulation to the periphery
94
What are the microscopic complications of long term diabetes?
- Diabetic eye disease
- Diabetic kidney disease
- Diabetic neuropathy
- Diabetic feet
95
What is the cause of diabetic eye disease?
- Due to diabetic retinopathy.
- Damage to blood vessels into the retina can lead to blindness.
- Damaged blood vessels may leak and form protein exudates in the retina or can burst to lead to bleeding into the eye. In addition new blood vessels may form which are weak and easily bleed
- Also arise from changes to lens due to osmotic effects of glucose and possibly cataracts
96
What is diabetic kidney disease?
- Kidney is affected by damage to glomeruli.
- Poor blood supply because of changes in kidney blood vessels
- Damage from infections the urinary tract which are more common in diabetics.
97
What is diabetic neuropathy?
Damage to peripheral nerves producing a variety of effects
- Change or loss of sensation
- Changes due to alteration in the function of the autonomic nervous system.
98
What is diabetic feet?
-Poor blood supply, damage to nerves and increased risk of infection all conspire to make the feet of the diabetics particularly vulnerable.
99
What is type 1 diabetes?
- Characterised by progressive loss of all or most of the pancreatic beta cells. It is rapidly fatal if not treated and must be treated with insulin. It is autoimmune
- Commonest type in young
100
What is type 2 diabetes?
- Affects a large number of usually older individuals
- Characterised by slow progressive loss of all or most of the pancreatic beta cells along with disorder of insulin secretion and tissue resistance to insulin. May be present for a long time before diagnosed
101
What can measurement of C-peptide be used for?
It is used to monitor any endogenous insulin secretion as it is released in equimolar amount with insulin.
102
What are the actions of aldosterone?
- Acts on distal tubules and collecting ducts of nephrons in the kidney causing reababsorpton of Na+ and water and secretion of K+ into tubular lumen. Upregulates the expression of the basolateral Na+/K+ pump.
- Upregulates the ENaCs in the collecting duct and also colon promoting Na+ absorption
103
Why should time always be recorded when taking cortisol measurements?
-Cortisol levels varies during the day from a peak at a 7am and a trough at 7pm so the time at which the measurement is taken should be repeated at the same time of day
104
What is the effect of over secretion AcTH on the adrenal glands?
Hyperplasia and over-production of cortisol
105
What are the clinical effects of excess cortisol secretion and why does it occur?
Cushing's syndrome. This is due to
- Increased activity of the adrenal cortex due to primary cortisol producing adrenal adenoma
- Disorders in the secretion of ACTH caused by a pituitary adenoma (Cushing's disease) or in rare cases ectopic secretion of ACTH from a tumour at a site remote from the pituitary.
106
What are the sign and symptoms of excess cortisol secretion?
-Hyperglycaemia (polyuria, polydipsia)
Increased muscle proteolysis and hepatic gluconeogenesis.
-Muscle weakness and thin arms and legs
Increased muscle proteolysis leads to wasting of wasting of proximal muscle and producing thin arms and legs and muscle weakness
-Buffalo hump
-Abdominal obesity
-Plethoric moon shaped face
-Acute weight gain
Increased lipogenesis in adipose use leading to deposition of fat in abdomen , neck and face
-Purple striae on the lower abdomen, upper arms and thigh
Due to catabolic effects on protein structure in the skin and leading to easy bruising because of thinning of skin and subcutaneous tissue
-Acne and bacterial infection
Immuno-supppresive and anti-inflammatory and anti allergic reactions of cortisol
-Back pain and collapse of ribs
Due to osteoporosis caused by disturbances in calcium metabolism and loss of bone matrix protein
-Hypertension
Mineralocorticoid defects of excess cortisol leads to sodium and fluid retention
107
What is the difference between Cushing's disease and Cushing's syndrome?
- Cushing's syndrome refers to generalised symptoms resulting from chronic excessive exposure to cortisol
- Cushing's disease refers to the specific case of benign ACTH secreting pituitary adenoma.
108
What is the common cause of Cushing's syndrome?
Patients receiving long term treatment with glucocorticoids from various chronic inflammatory conditions. Examples include Hydrocortisone, Dexamethasone and Prednisolone
109
What are the clinical effects of too little cortisol and what are the possible causes?
Decreased activity of the adrenal cortex (Addison's disease) may be due to
- Disease of adrenal cortex such as auto immune destruction reduces glucocorticoids and mineral corticoids
- Disorders in pituitary or hypothalamus that lead to decreased secretion of ACTH or CRF - affects glucocorticoids
110
What are the symptoms of Addison's disease?
- Lethargy
- Extreme muscular weakness
- Extreme dehydration
- Anorexia
- Vague abdominal pain
- Weight loss and occasional dizziness
- Increased skin pigmentation - Due to increased in ACTH as well as other products of POMC which stimulates melanocytes to produce melanin
- Decreased blood pressure due to sodium and fluid depletion. Postural hypotension
- Hypoglycaemic - lack of glucocorticoid
111
What is Addison's crisis?
An acute life threatening emergency due to adrenal insufficiency. Precipitated by
- Sever stress
- Salt depravation
- Infection
- Trauma
- Cold exposure
- Over exertion
- Abrupt steroid drug withdrawal
112
What is Conn's syndrome?
Aldosterone secreting adrenal adenoma. Can be caused by one or both adrenal glands.
113
What are the signs of hyperaldosteronism?
- Hypertension at young age
- Hypokalaemia
- Stroke
- Hypernatraemia
- Left ventricular hypertrophy
114
What can be used as a marker for primary hyperaldosteronism?
- High aldosterone with decreasing renin
| - High aldosterone:Renin ratio
115
What is congenital adrenal hyperplasia?
An autosomal recessive disorder causing adrenal crisis and ambiguous genitalia.
Caused by a block in adrenal cortex pathway due to an enzyme defect and result in increased secretion of androgens
116
What is the effect of the lack of enzyme in CAH?
- Low cortisol and aldosterone
| - High male hormone
117
What is the presentation in CAH?
- Hypotension
- Hyponatraemia
- Hyperkalaemia
- Hypoglycaemia
- Virilisation
118
What are the types of primary hyperaldosteronism?
- Aldosterone secreting adrenal adenoma (Conn's syndrome)
| - Bilateral idiopathic adrenal hyperplasia
119
What is the treatment for adrenal crisis?
- Treated with venous cortisol (hydrocortisone)
- Rapid Fluid replacement to avoid death.
- Correction of hypoglycaemia
- Search for precipitating cause (Addison's for example)
120
What is the most common enzyme in ACH?
21 hydroxylase
121
What are the types of secondary hyperaldosteronism?
- Renin producing tumour
| - Renal artery stenosis
122
What is the indication of secondary hyperaldosteronism?
- High renin levels
| - Low aldosterone:renin ratio
123
What are the treatment for hyperaldosteronism?
Depends on the type
- Aldosterone-producing adenomas removed by surgery
- Spironolactone (mineralocorticoid receptor antagonist)
124
What is the common enzyme defect in CAH?
21-hydroxylase deficiency
125
What are the clinical features of Addison's crisis?
- Dehydration
- Coma
- Pigmentation
- Hypotension
- Vascular collapse
126
What are the characteristics of pheochromocytoma?
- Severe hypertension
- Headaches
- Palpitations
- Diaphoresis
- Anxiety
- Weight loss
- Elevated blood glucose
- SUDDEN DEATH
127
What are the tests for suspected adrenal insuffiency?
- Electrolytes : low Na, High K in aldosterone deficiency
- 0900 basal cortisol low : when it should be high
- Stimulation test : inject with synthetic ACTH (synacthen)
128
What are the tests for suspected adrenal insufficiency?
- Electrolytes : low Na, High K in aldosterone deficiency
- 0900 basal cortisol low : when it should be high
- Stimulation test : inject with synthetic ACTH (synacthen)
129
What are the test for suspected adrenal hormone excess?
- Electrolytes : high BP, low K
- Midnight cortisol high - should be low
- 24h urine cortisol high
- Suppression test - failure to suppress
- Androgens and derivatives high
130
What is the biochemical assessment for adrenal medulla?
- 24h urine catelchoamines - adrenaline, noradrenlaine, dopmine, 3-methyl-tyramine
- 24h urine metanephrines - met adrenaline, normatadrenaline (metabolites of adrenaline and noradrenaline)
- Plasma metanephrines - more sensitive than 24h urine
avoid certain foods such as coffee, coke, bananas, chocolate, vanilla
131
What are the different radiological assessment of adrenal disease?
- CT scan
- MRI scan
- MIBG scan
- PET scan
132
How is Addison's disease controlled?
Lifelong treatment with glucocorticoid (prednisone, hydrocortisone) and mineral corticoid (fludrocortisone)
Education to prevent crises - double dose of glucocorticoid at times of illness, Steroid card and bracelet and Emergency hydrocortisone if vomiting.
133
What are the symptoms of ACTH deficiency and when does in occur?
- Occurs in any case of hypopituitarism
- Similar symptoms to adrenal failure
- No pigmentation as ACTH not raised
- No hyperkalaemia as no mineralocorticoid deficiency
- Hyponatraemia due to effect of cortisol on free water secretion.
134
What is steroid-induced hypoadrenalism?
ACTH suppressed with long term steroids so abrupt withdrawal can cause hypo-adrenal crisis
Important to consider in any unwell patients on steroids
135
What is the presentation of adrenal cushing's syndrome?
```
ACTH suppressed
Androgenic symptoms may be present such as
-Hirsutism
-Acne
-Greasy skin
```
136
What are the treatment for phaeochromocytoma?
- Alpha blockade (phenoxybenzamine)
- Betablackage (bisoprolol)
- Surgical excision
137
What is an indication of nephropathy?
Increase in the amount of protein in urine. (microalbuminuria)
138
What is the principle components of the calcium hydroxyapatite crystals?
Calcium and phosphate
139
What is the major portion of the mineral phase of the bone made of?
Calcium Hydroxyapatite crystals
140
What regulates the calcium and phosphate levels?
- Parathyroid Hormone
- Calcitriol
- Calcitonin
141
Where is most calcium located?
Bone. 1Kg
142
What is a major source of calcium in the diet?
Dairy products
143
What states does calcium exist in plasma?
- As free ionised Species
- Bound to anionic sites on serum proteins
- Complexed with low molecular weight organic anions
144
What is the result of hypocalcaemia?
Results in hyperexcitiability in the nervous system including the neuromuscular junction leading
- Parathesia
- Tetany
- Paralysis
- Convulsions
145
What is the result of chronic hypercalcaemia?
- Formation of kidney stones
- Constipation
- Dehydration
- Kidney damage
- Tiredness
- Depression
146
What are the actions of parathyroid hormone?
- Raises calcium levels in short term regulation
- Reduced renal phosphate reabsorption
- Stimulates calcium reabsorption in kidney
- Stimulates bone resorption and increased calcium release into circulation
- Stimulates hydroxylation of
147
What is action of Vitamin D?
- Increase intestinal absorption of dietary calcium and renal reabsorption of calcium
- Increase bone resorption
148
What is action of calcitonin?
-Counteracts the effects of PTH
149
How does hypercalcaemia affect plasma calcium levels?
- Decreased PTH secretion
- Less calcitriol from kidney so less calcium from gut and calcium reabsorption in the kidney
- Less Ca2+ taken from the gut
- Less bone breakdown and increase bone building
- This all acts to decrease the plasma calcium levels.
150
How does hypocalcaemia affect plasma calcium levels?
- Increased PTH secretion
- Increased calcitriol from the kidney which means more calcium absorbed form the gut and increase calcium reabsorption in the kidney.
- Increased bone breakdown and decreased bone building
- This all acts to increase the plasma calcium levels
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What is the effect of chief cells?
Produce parathyroid
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What is the active form of vitamin D and how is it produced?
- Vitamin D from the sun exposure, food and supplements is biologically inert
- Must undergo two hyrodxylation reaction to be activated in the body to form calcitriol
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What is the half life of parathyroid hormone?
4 minutes
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What can be secreted by some tumours which can lead to hypercalcaemia?
Parathyroid hormone related peptide.
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Why doesn't calcitriol levels increase in humeral hypercalcaemia of malignancy?
Parathyroid hormone related peptide doesn't cause an increase in calcitriol concentration as it doesn't increase renal C-1 hydroxylase.
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True/False. Hypo or Hyper secretion of Calcitonin has a large effect on calcium.
False. Has very little function. Thyroid gland removal has no apparent effect on calcium homeostasis
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When is calcitonin suggested to have an impact?
During pregnancy it is suggested to preserve the maternal skeleton.
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Can parathyroid be stored?
Yes but has very little stores. It is synthesised continually
-Chief cells synthesise the hormone and degrade it.
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How does increase calcium levels affect parathyroid release?
- Increased serum calcium levels.
- Binding to specific receptor
- GPCR activated
- Decrease in transcription and release of parathyroid
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What does the body prioritise calcium levels or structural integrity?
Maintaining serum calcium is more important to the body than maintaining structural integrity.
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What are the actions of PTH in the bone referencing the cells?
Osteolysis
- PTH induces osteoblastic cells to synthesise and secrete cytokines on cell surface
- Cytokines stimulate differentiation and activity in osteoclasts and protect them from apoptosis
- PTH decreases osteoblasts activity exposing bony surface to osteoclasts
- Reabsorption of mineralised bone and release of phosphate and Ca2+ into extracellular fluid
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Why does the reabsorption of calcium and reabsorption of phosphate need to be regulated?
- Calcium and phosphate need to be regulated as they can be reacted.
- PTH increases calcium reabsorption and decrease phosphate reabsorption to stop the reaction and formation of hydroxyapatite crystals in kidney.
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How is Calcitriol formed?
- Cholecalciferol is hydroxylated in the liver to form 25-hydroxycholecalciferol
- 25-hydroxycholecalciferol is hydroxylated to form 1,25-dihydrocholecalciferol(calcitriol) using the enzyme 1-alpha-hydroxylase
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Which cells secrete calcitonin?
-Secreted by parafollicular cells or C cells of thyroid gland
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What are the pathological consequences of hypocalcaemia?
Hyperexcitability of neuromuscular junction
- Pins and needles
- Tetany
- Paralysis
- Convulsions
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What are the pathological consequences of hypercalcaemia?
| hyperparathyroidism
- Kidney stones
- Kidney damage
- Constipation
- Dehydration
- Tiredness
- Depression
- Polyuria
stones, mones and groans
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What is calcium in the clotting cascade?
Factor IV
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What has to be given to recipients of massive blood transfusions?
Intravenous Calcium. To allow clotting
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What are the common cancers that metastasise to bone causing lytic lesions and hypercalcaemia?
- Breast
- Lung
- Renal
- Thyroid
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Prostate cancer causes osteoblastic metastases that does not cause hypercalcaemia. True/False
True
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What is the aetiology of hypercalcaemia in a hospital setting?
- Malignant osteolytic bone metastases
| - Multiple myeloma
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What are the common sites for metastases?
Vertebrae, Pelvis, Proximal parts of the femur, Proximal part of the humerus and Skull. More than 90% of metastases are found in this distribution
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What is primary hyperparathyroidism?
One of the 4 parathyroid glands develops an adenoma and secretes excessive parathyroid hormone. This causes serum calcium rise and serum phosphate to fall
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What is secondary hyperparathyroidism?
All 4 parathyroid glands become hyperplastic.
-Due to vitamin D deficiency. Renal failure or dietary
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What can occur when the thyroid gland is taken out in surgery?
Accidentally take out the parathyroid
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What does an increased serum alkaline phosphatase show?
Increased bone turnover
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What does sever hypercalcaemia result in if polyuria continues?
Dehydration which exacerbates hypercalcaemia. this can lead to
- Lethargy
- Weakness
- Confusion
- Coma
- Renal failure
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What is the mainstay treatment for dehydration as a result of severe hypercalcaemia?
Rehydration is the mainstay of treatment.
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When is symptomatic hypocalcaemia seen?
Seen mostly in post total-thyroidectomy patients. Symptoms can develop when serum calcium falls below 2.10 mmol/l and can start within 6 hours of thyroidectomy.
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What are the sensory symptoms of hypocalcaemia?
Tingling around the mouth and in fingers
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Why does hypocalcaemia need treating quickly?
Hypocalcaemia can kill due to laryngeal muscle tetany, so needs treating quickly
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What is osteoporosis?
Decreased bone density with a normal ratio of mineral to matrix. There is normal bone but not enough of it.
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What does osteoporosis lead to?
Leads to brittle bones that are prone to fractures
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What is osteomalacia?
The ratio of mineral to matrix is decreased. It is an abnormality that can affect bone building in children or bone mineralisation in adults. Leads to soft bones that are prone to bending.
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What can cause osteomalacia?
- Dietary, environmental. In children it is called rickets
| - Chronic renal disease - renal osteodystrophy
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What are the symptoms of osteomalacia in adults?
- Bone pain
- Muscle weakness
- May lead to deformity
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What are the risks factors for osteoporosis?
- Post menopausal women
- Low body mass index (BMII)
- Long-term oral steroid use
- Heavy drinking
- Smoking
- Prolonged inactivity such as bed rest
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What are the 2 main levels of control of energy ?
- Changing activity of enzymes in metabolic pathways
| - Altering which substances can enter cells from the blood
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What is metabolic syndrome?
A cluster of most dangerous risk factors associated with cardiovascular disease
- Diabetes
- Raised plasma glucose
- Abdominal obesity
- High cholesterol
- Blood pressure
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What is the cause of metabolic syndrome?
```
Insulin resistance
Central obesity
Genetics
Physical inactivity
Ageing
```
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What are the acute complications of hypoglycaemia?
- Coma
| - Brain needs glucose. Caused by hypoglycaemic therapy
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How does insulin resistance occur in the young?
Insulin resistance present before onset of hyperglycaemia and development of overt type 2 diabetes
Initially:
-Beta cells compensate by increasing insulin production in order to maintain normal blood glucose
Eventually
-Beta cells unable to maintain increased insulin production so impaired glucose intolerance
Finally
-Beta cells dysfunction leads to relative insulin deficiency so overt type 2 diabetes
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What does insulin do?
Increases glucose uptake inc ells and glycogen synthesis
- In the liver it increases glycogen synthesis by stimulating glycogen formation and by inhibiting breakdown
- In muscle it increase uptake of amino acids promoting protein synthesis
- In liver inhibits breakdown of amino acids
- In adipose tissue increases the storage triglycerides
- Inhibits the breaks of fatty acids
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How is diabetes diagnosed?
- Random venous plasma glucose contraction of ≥ 11.1 mmol/L or
- A fasting plasma glucose concentration ≥7.0 mmol/L (whole blood ≥6.1 mmol/L) or
- Plasma glucose concentration ≥11.1 mmol/L 2 hours after 75g anhydrous glucose in oral glucose tolerance test
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What is paracetamol broken down into within it therapeutic window?
Glucuronide and sulphites
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How does increased alcohol intake exacerbate gout?
- Decreased utilisation of lactate by liver cells
- Increased accumulation in the blood and may cause lactic acidosis
- Increased levels of lactate decrease kidneys ability to excrete uric acid which may exacerbate gout
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How does fasting hypoglycaemia occur with increased alcohol intake?
- Low NAD+ level combined with the inability of the liver cells to use lactate and glycerol
- Gluconeogenesis cannot be activated and fasting hypoglycaemia may become a serious problem
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What are used as markers of damaged hepatocytes?
- AST
- ALT
- Gamma Glutamyl Transpeptidase
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Why are mitochondrial DNA paticularly sensitive to ROS damage?
mtDNA is situated near the inner mitochondria membrane where ROS are formed. It is also not protected by histones
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What is a Heinz body?
Red blood cels with precipitated cross linked haemoglobin
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How do free radical scavenger battle oxidative stress?
Donate Hydrogen atom to free radicals in non enzymatic reaction
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What is chronic granulomatous disease?
Defect in NADPH oxidase complex which causes enhanced susceptibility to bacterial infections
- Atypical infections
- Pneumonia
- Abscesses
- Impetigo
- Cellulitis
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What is the action of glutamine synthetase and glutaminase?
- Conversion of glutamate to glutamine using ammonium ions.
- Glutamine is transported to the liver and the kidney where it is hydrolysed by glutaminase releasing ammonia
- Ammonia can disposed of in the urine or converted to urea
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What is the significant of the glutamate dehydrogenase enzyme?
- Catalyses the reaction of ammonia and alpha ketoglutarate to form glutamate in mitochondria.
- Remove alpha ketoglutarate from the TCA cycle which slows, disrupting energy supply to brain cells
