BIOCHEMICAL INVESTIGATION OF HTN Flashcards
INTRODUCTION
Hypertension can be defined as Systolic BP of 140mmhg or more OR a Diastolic BP of 90mmhg or more OR taking of antihypertensive medication
Normal; Systolic lower than 120 and Diastolic lower than 80
PreHypertension; 120-139, 80-89
Stage 1; 140-159, 90-99
Stage 2; Systolic greater than 160 and diastolic greater than 100mmhg
AHA(American Heart Association)
Classsifies it into 2
Elevated BP; when systolic is 120-129 and diastolic is lower than 80
Stage 1 HTN; 130-139 for systolic and diastolic 80-89mmhg
HYPERTENSION MAY BE
Primary; Due to environmental and Genetic causes
Secondary; Due to and underlying aetiology which could be endocrine, renal and vascular causes
SUGGESTIVE SIGNS OF SECONDARY HTN
1.Severe or resistant Htn
2. Age of onset lesser than 30yrs
3. Malignant or accelerated Htn (sudden rise in Bp associated with target organ damage)
4. Sudden acute rise of Bp from prev stable readings
SECONDARY CAUSES OF HTN (ENDOCRINE CAUSES PART 1)
1.)PRIMARY ALDOSTERONISM
—Aldosterone producing Adenomas (APA)
—Idiopathic Adrenal Hyperplasia(IAH)
—(GRA) Glucocorticoid Remedial Aldosteronism
Aldosterone production exceeds the body’s requirements and is unchecked by the renin-angiotensin II system(RAAS), resulting in increased Na+ reabsorption via amiloride-sensitive epithelial Na channels(ENaC) within the distal nephron.
TESTS
a. Plasma K+; hypokalemia in a hypertensive patient is a valuable clue of the presence of PA
b. Urine K+; Kaliuria may be observed
c. Aldosterone/renin ratio(ARR): MOST RELIABLE SCREENING TEST. Plasma aldosterone con of 10ng/dl and plasma renin activity of 1ng/dl/h highly suggests PA
Dynamic tests like; Captopril test, fludrocortisone suppression test and Saline infusion test can also be carried out
(Other conditions of Mineralocorticoid excess)
2.) CONGENITAL ADRENAL HYPERPLASIA
Deficient secretion of cortisol
Approximately 90% of CAH cases are caused by 21- hydroxylase deficiency, which does not result in hypertension.
Deficiencies of 11b-hydroxylase or 17a-hydroxylase cause hypertension and hypokalemia because of hypersecretion of the mineralocorticoid Deoxycorticosterone (DOC).
—11b-hydroxylase deficiency causes approximately 5% of all cases of CAH
Tests:
+Plasma DOC, 11-deoxycortisol, androstenedione, testosterone, and (DHEA-S) are elevated.
+Germline mutation testing.
—17a-Hydroxylase deficiency is a very rare cause of CAH;
Tests:
+ Plasma DOC and corticosterone are elevated BUT Plasma androstenedione, testosterone, DHEA-S, aldosterone, and cortisol are either low or at the lower quartile of their respective references ranges.
+Genetic testing.
3.) DOC producing tumor
Tests: A high level of plasma DOC and a large adrenal tumor appearing on computed tomography (CT) confirm the diagnosis
4.) Apparent Mineralocorticoid Excess Syndrome
TESTs; Abnormally high ratio if Cortisol to Cortisone in a 24 hr urine Sample (10 fold the normal value)
5.) LIDDLE SYNDROME
It is a RENAL disorder that presents similar to PA including HYPERTENSION, HYPOKALEMIA AND KALIURESIS. However plasma aldosterone and Renin are low and its been termed PSEUDO ALDOSTERONISM
TESTS;
+ low aldosterone and renin levels in a hypokalemic hypertensive patient should consider Liddle syndrome.
+ Genetic testing.
(Done with Mineralocorticoid excess)
6.) PHEOCHROMOCYTOMA
Cathecolamine secreting tumors
—10% are outside the adrenal medulla, 10% are bilateral and 10% are malignant
— it should be excluded in a young adult with paroxysmal or persistent HTN for no reason or Refractory HTN or showing the classic TRIAD (Headaches, Sweating and Tachycardia associated with HTN)
— potentially curable by surgery
TESTS;
+Daily urinary catecholamines— (adrenaline, noradrenaline and dopamine)
+Urinary METANEPHRINES— (which are metabolites of catecholamines) are PREFERABLE because they are more sensitive than catecholamines.
Dynamic tests: Clonidine or Pentolinium suppression tests: In normal individuals, concentration of urinary and plasma catecholamines should decrease after the administration of a suppressing agent.
In phaeochromocytoma, there is autonomous catecholamine secretion and no suppression.
Imaging studies include abdominal computerized tomography, magnetic resonance imaging (MRI)
SECONDARY CAUSES OF HTN
ENDOCRINE CAUSES (PART 2)
Those that aren’t Mineralocorticoid (includes pheochromocytoma)
7.) NEUROBLASTOMAS
Malignant tumors in the Sympathetic Nervous Tissue ussually occuring in Children
—About 40% occurs in the adrenal medulla and 60% are extra adrenal
—Plasma Cathecolamine conc may be as high as in patients with pheochromocytoma
The METABOLITE OF Dopamine HVA (Homovanillic acid) is the Urinary marker of this disease. I.e Urinary HVA is the marker of this DX
- CUSHING’s SYNDROME
Characterized by excessive circulating glucocorticoids
May be iatrogenic or from excessive steroid therapy
—HTN occurs in 75 - 80% of patients with Cushing’s syndrome
Tests: plasma cortisol, 24 hr urinary cortisol, late night salivary cortisol, dexamethasone suppression tests, plasma ACTH assay.
9.) THYROID DYSFUNCTION
Hyper and Hypothyroidism
TESTS of thyroid dysfunction include: +free and total plasma T3 and T4 assay
+plasma TSH assay
+anti-TSH assay
+assays for antibodies to thyro-peroxidase, and thyroglobulin (anti-TPO, anti-tg),
+thyroid binding globulin assays, radioactive iodine studies.
9.) ACROMEGALY
Tests:
+Plasma GH
+plasma insulin-like growth factor 1 assays
+Glucose suppression test.
11.) Hypercalcemia and primary hyperparathyroidism.
The most common cause of hypercalcemia is primary hyperparathyroidism.
Hypercalcemia is associated with an increased frequency of hypertension. The frequency of hypertension in patients with primary hyperparathyroidism varies from 10% to 60%.
TESTS;
+Serum parathyroid hormone assay
+serum calcium
+24-hour urinary calcium excretion.
RENAL AND VASCULAR CAUSES
RENAL;
—Secondary hyperaldosteronism reflects pathologicall y elevated aldosterone levels due to activation of the renin-angiotensin axis;
Situations associated with secondary aldosterone excess include renal artery stenosis from atherosclerosis or fibromuscular dysplasia, renal infarction, volume depletion states, renal hypoperfusion related to cardiac or hepatic failure, (rarely) primary overproduction of renin from a juxtaglomerular tumor.
Other renal causes of hypertension:
Include renal parenchymal diseases e.g.
—Polycystic kidney disease
—Chronic kidney disease
—Urinary tract obstruction etc.
VASCULAR;
— Coarctation of Aorta
— Vasculitis
— Collagen Vascular Diseases
DRUGS TOO
Drugs that can cause hypertension include: Alcohol, Cocaine, Cyclosporine, tacrolimus, NSAIDs, Erythropoietin, Adrenergic medications, Decongestants containing ephedrine, Herbal remedies containing licorice , Nicotine, Oral contraceptive pills etc.
OBSTRUCTIVE SLEEP APNEA(OSA)
OSA is repeated partial (hypopnea) or complete (apnea) airway closure during sleep.
It is characterized by sleep disruption, intermittent hypoxemia and hypercapnea, and changes in intrathoracic pressure.
— OSA is strongly associated with hypertension; this is particularly true with resistant or difficult-to-treat hypertension.
It is more likely in persons with
—body mass index >30 kg/m2
—older >65 years
—have an enlarged neck circumference (men, >43 cm; women, >37 cm), a small upper airway, and/or retrognathia or micrognathia.
TESTS:
+Polysomnography. The definitive diagnosis of OSA requires evaluation by polysomnography. Historically, sleep technicians monitored patients in a sleep laboratory. Recently, however, there is growing use of home sleep monitoring systems for diagnosing OSA.
