2: Hypertension Flashcards
1
Q
Types of hypertension
A
Primary
- unknown cause
- interacting genetic and environmental factors
Secondary
Malignant
- rapidly rising blood pressure leading to death in 1-2 years
2
Q
Causes of secondary hypertension
A
○ Renal § Renal artery stenosis § Glomerulonephritis § Chronic renal disease § Renal vasculitis § Polycystic disease ○ Endocrine § Adrenocorticoid hyperfunction § Exogenous hormones § Phaeochromocytoma § Acromegaly § Hyperthyroidism ○ Neurologic § Raised ICP § Sleep apnoea § Acute stress § Psychogenic ○ Cardiovascular § Coarctation of aorta § Polyarteritis nodosa § Increased vascular volume § Increased cardiac output ○ Pre-eclampsia
3
Q
What are the main factors influencing blood pressure regulation?
A
- BP = CO x TPR (Total Peripheral Resistance)
- CO = SV x HR
- Renin secreted by the kidneys in response to decreased blood pressure in afferent arterioles
○ Renin cleaves angiotensinogen to angiotensin I
○ Endothelial catabolism produces angiotensin II
○ Regulates blood pressure by increasing vascular SMC tone and increasing adrenal aldosterone secretion
○ Increasing renal sodium resorption
4
Q
Mechanisms of primary hypertension
A
Result of interacting genetic and environmental factors
Blood volume increased by sodium and mineral corticoids
Insufficient renal sodium excretion
Vasoconstrictive influences
Environmental factors
5
Q
Mechanisms of secondary hypertension
A
○ Renovascular
§ Renal artery stenosis causes decreased glomerular flow and pressure in afferent arteriole of the glomerulus
§ Induces renin secretion leading to increased blood volume and vascular tone via angiotensin and aldosterone pathways
○ Primary hyperaldosteronism
§ Idiopathic
§ Aldosterone-secreting adrenal adenomas
○ Single gene disorders
6
Q
Morphological features of hypertension
A
- Hyaline arteriolosclerosis
○ Luminal narrowing - intima compressed by media
○ Pink hyaline thickening- Hyperplastic arteriolosclerosis
○ Laminated onion skin thickening of walls - consists of SMCs with thickened reduplicated basement membrane
○ Luminal narrowing
○ Thickened smooth muscle cells due to basement membrane reduplication
○ More likely seen in sever or malignant hypertension - Malignant hypertension
○ Fibrinoid deposits
○ Vessel wall necrosis
○ Neutrophil infiltration
○ Circumferential bright pink area of necrosis with protein deposition and inflammation
- Hyperplastic arteriolosclerosis
7
Q
Features of pressure-overload hypertrophy
A
○ Increased afterload ○ Causes § Hypertension § Valvular stenosis ○ New sarcomeres predominantly assemble din parallel to long axes of cells -> concentric increase in wall thickness
8
Q
Features of volume-overload hypertrophy
A
○ Increased preload ○ Causes § Valvular regurgitation § Myocardial infarction ○ New sarcomeres assembled in series within existing sarcomeres -> ventricular dilation
9
Q
Features of physiological hypertrophy
A
○ Proportional increase in cell length and width
○ Proportional increase in muscle and lumen size
§ Increased capillary density
○ Normal cardiac function
○ Leads to decreased resting HR and BP
○ Seen in children, pregnancy and athletes
Associated with aerobic exercise
10
Q
Consequences of hypertrophy
A
○ Ischaemia-related decompensation -> cardiac failure ○ Interstitial fibrosis ○ Arrythmias ○ Ischaemic heart disease ○ Sudden cardiac death
11
Q
Causes of left sided heart failure
A
§ Ischaemic heart disease
§ Hypertension
§ Aortic and mitral valvular disease
§ Primary myocardial disease
12
Q
Clinical features of left-sided heart failure
A
○ Symptoms § Dry cough § Dyspnoea ○ Signs § 3rd or 4th heart sounds § Tachycardia § Pulmonary oedema - course crackles on auscultation § Atrial fibrillation
13
Q
Causes of right-sided heart failure
A
Left-sided heart failure
Cor pulmonale
14
Q
Clinical features of right-sided heart failure
A
○ Symptoms Leg swelling Weight gain Fatigue ○ Signs Cyanosis Distended neck veins Marked hepatojugular reflex Ascites Confusion and irritability
15
Q
Define cor pulmonale
A
Abnormal enlargement of the right side of the heart as a result of disease of the lungs of pulmonary blood vessels
16
Q
Causes of cor pulmonale
A
○ Diseases of pulmonary parenchyma § COPD § Pulmonary fibrosis § Pneumoconiosis § Cystic fibrosis § Bronchiectasis ○ Diseases of pulmonary vessels § Recurrent PE § Primary pulmonary hypertensin ○ Disorders affecting chest movement § Kyphoscoliosis § Marked obesity § Neuromuscular diseases ○ Disorders inducing pulmonary arterial constriction § Metabolic acidosis § Hypoxemia § Chronic altitude sickness
17
Q
Morphological features of left-sided heart failure
A
§ Heart □ Depends on disease process □ Hypertrophy/dilation of left ventricle □ Secondary dilation of left atrium □ Nonspecific microscopic changes § Lungs □ Heavy wet lungs □ Widening of alveolar septa □ Haemosiderin-laden macrophages
18
Q
Morphological features of right-sided heart failure
A
○ Heart § Depends on cause § Hypertrophy / dilation of right ventricle ○ Liver and portal systems § Congestive hepatomegaly § Centrilobular necrosis § Cardiac cirrhosis § Congestive splenomegaly ○ Pleural, pericardia and peritoneal spaces § Effusions ○ Subcutaneous tissues § Oedema
19
Q
Factors influencing movement of fluid across capillary walls
A
- Hydrostatic pressure ○ Blood hydrostatic pressure ○ Interstitial hydrostatic pressure (negligible-lymphatic system) - Oncotic pressure ○ Blood oncotic pressure ○ Interstitial oncotic pressure (negligible- few proteins in interstitial fluid so always low) - Permeability of vessel wall ○ Inflammation
20
Q
Categorisation of oedema
A
- Exudate = protein rich
- Transudate = protein poor
21
Q
Clinical features of oedema
A
- Peripheral oedema ○ Often dependent (affected by gravity) ○ Common in legs/ankles or sacrum ○ May be pitting ○ Tight and shiny appearance ○ Potential underlying cardiac/renal disease ○ Can impair wound healing - Angioedema ○ Occurs on hands, feet, eyes, lips, tongue, airways and genitals ○ Reaction to allergen, idiopathic or genetic ○ Swelling of throat can be fatal - Pulmonary oedema ○ SOB, especially when lying down ○ Haemoptysis ○ Often 2-3 times normal weight ○ Frothy, blood-stained fluid on sections (air, oedema and RBCs) ○ Consequences § Disrupts gas exchange -> hypoxia § Predisposes to bacterial infection - Cerebral oedema ○ Causes § Trauma § Ischaemic stroke § Tumour obstructing fluid drainage § Infections- encephalitis § Haemorrhage § High altitude ○ Consequences § Widened gyri § Narrow sulci § Can be life threatening § Herniation § Compression of vascular supply
22
Q
Classification of pulmonary oedema
A
- Haemodynamic oedema
○ Caused by increase in hydrostatic pressure, a decrease in oncotic pressure
§ Increased hydrostatic pressure
□ Left-sided heart failure
□ Volume overload
□ Pulmonary vein obstruction
§ Decreased oncotic pressure
□ Hypoalbuminemia
□ Nephrotic syndrome
□ Liver disease
□ Protein-losing enteropathy
○ Fluid accumulates at base of lung first - where hydrostatic pressure is highest- Alveolar wall injury
○ Increased capillary permeability due to microvascular injury
§ Direct injury
□ Infections - bacterial pneumonia
□ Inhaled gases - high concentrations of oxygen, smoke
□ Liquid aspiration - gastric contents, near-drowning
□ Radiation
□ Lung trauma
§ Indirect injury
□ SIRS - sepsis, burns
□ Blood transfusion relation
□ Drugs and chemicals - chemotherapeutic agents, heroin, cocaine - Undetermined origin
○ High altitude
○ Neurogenic pulmonary oedema - CNS trauma
- Alveolar wall injury
23
Q
Define nephrosclerosis
A
- Renal pathology associated with sclerosis of renal arterioles and small arteries
- Strongly associated with hypertension - both cause and consequence of nephrosclerosis
24
Q
Pathogenesis of nephrosclerosis
A
○ Medial and intimal thickening - response to haemodynamic changes, aging, genetic defects
○ Hyalinisation of arteriolar walls - caused by extravasation of plasma protein through injured endothelium and increased deposition of basement membrane matrix
○ Narrowed lumen
○ Decreased perfusion to renal parenchyma
○ Focal ischaemia
○ Glomerulosclerosis and chronic tubulointerstitial injury
○ Decreased functional renal mass
25
Features of malignant nephrosclerosis
```
○ SBP> 180mmHg or DBP > 120 mmHg
○ Endothelial damage
○ Increases fibrinogen permeability -> fibrinoid necrosis
○ Increased permeability to proliferative factors -> hyperplastic arteriolosclerosis
○ Onion skin intima
○ Necrotic media infiltrated by fibrin
○ Narrowed lumen
○ Reduced renal parenchyma
○ RAAS activation and increased BP
```
26
Morphological features of nephrosclerosis
- Gross
○ Normal or moderately reduced in size
○ Cortical surfaces have fine granularity - due to cortical scarring and shrinking
- Histologically
○ Narrowing of lumens of arterioles and small arteries by hyaline arteriolosclerosis
○ Microscopic subcapsular scars with sclerotic glomeruli and tubular dropout
○ Interlobular and arcuate arteries show medial hypertrophy, replication of internal elastic lamina and increased myofibroblast tissue in intima
○ Consequences of vascular narrowing
§ Foci of tubular atrophy and interstitial fibrosis
§ Variety of glomerular alterations
□ Collapse of GBM
□ Deposition of collagen within Bowman space
□ Periglomerular fibrosis
□ Total sclerosis of glomeruli
§ Wedge shape infarcts or regional scars
27
Clinical features of nephrosclerosis
Features of CKD
§ Stages 1/2 = asymptomatic
§ Stages 3/4 = oedema (Na+ retention), fatigue ( reduced EPO release), pruritis (uraemia), anorexia
§ Stage 5 = oliguria (reduced GFR), ecchymosis (uraemia), confusion (uraemia), insomnia
○ Features of hypertension
§ Stage 1 = no signs of end organ damage
§ Stage 2 = LV hypertrophy, hypertensive retinopathy, atherosclerosis
§ Stage 3 = angina, MI, heart failure, retinal haemorrhages, exudates, papilloedema, stroke, aneurysm, vascular dementia
28
Groups at risk of nephrosclerosis
```
○ African descent
○ More severe hypertension
○ Diabetes mellitus
○ Older age
○ Chronic kidney disease
○ glomerulonephritis
```
29
How does renal artery stenosis cause hypertension?
- Increased production of renin from ischaemic kidney
○ Reduced renal perfusion detected by juxtaglomerular apparatus
○ Increased renin converts angiotensinogen to angiotensin I
○ ACE converts angiotensin I to angiotensin II
○ Aldosterone from adrenal cortex
§ Na+ and H2O retention
§ Increased circulating volume
○ Vasoconstriction
§ Increased BP
○ Increased perfusion pressure
30
Morphological features of renal artery stenosis
```
- Commonly caused by atheromatous plaque
○ Concentrically placed
○ Superimposed thrombosis
- Fibromuscular dysplasia
○ Fibrous or fibromuscular thickening involving intima, media or adventitia
- Ischaemic kidney
○ Diffuse ischaemic atrophy
○ Crowded glomeruli
○ Atrophic tubules
○ Interstitial fibrosis
○ Focal inflammatory infiltrates
```
31
Clinical features of renal artery stenosis
○ Bruit on auscultation of affected kidney
○ Features of CKD
§ Stages 1/2 = asymptomatic
§ Stages 3/4 = oedema (Na+ retention), fatigue ( reduced EPO release), pruritis (uraemia), anorexia
§ Stage 5 = oliguria (reduced GFR), ecchymosis (uraemia), confusion (uraemia), insomnia
○ Features of hypertension
§ Stage 1 = no signs of end organ damage
§ Stage 2 = LV hypertrophy, hypertensive retinopathy, atherosclerosis
§ Stage 3 = angina, MI, heart failure, retinal haemorrhages, exudates, Papilloedema, stroke, aneurysm, vascular dementia
32
At risk groups for renal artery stenosis
```
○ Atherosclerosis
§ Most common cause of RAS
§ Commonly causes renal impairment
§ > 50 years old
§ Male > Female
§ Vascular risk factors
○ Fibromuscular dysplasia
§ 2nd most common cause of RAS
§ Rarely causes renal impairment
§ 15 -50 year olds
§ Female > Male
§ Vascular risk factors
```
33
What are the causes of Cushing syndrome?
- Too much cortical
- Majority administration of exogenous glucocorticoids
- ACTH-dependent
○ Pituitary adenoma = Cushing disease
○ Ectopic corticotrophin syndrome
- ACTH-independent
○ Adrenal adenoma or carcinoma
34
Features of Cushing syndrome
- Fat pad "buffalo" hump
- Think arms and legs
- Thin skin -> bruising/tearing
- Stretch marks
- Extra face and body hair
- Thinning hair
- Red cheeks
- Round moon face
35
What are the morphological features of the main lesions of Cushing syndrome?
- Pituitary shows changes regardless of course
○ Crooke hyaline change
§ Normal granular basophilic cytoplasm of ACTH producing cells in anterior pituitary becomes homogenous and paler
§ Results of accumulation of intermediate keratin filaments in cytoplasm
- Adrenals
○ Cortical atrophy
§ Exogenous glucocorticoids = bilateral cortical atrophy
○ Diffuse hyperplasia
§ ACTH-dependent Cushing syndrome
§ Adrenal cortex diffusely thickened and variably nodular
§ Lipid poor zona reticularis comprising of compact eosinophilic cells surrounded by outer zone of vacuolated lipid rich cells
○ Macronodular hyperplasia
§ Adrenals almost entirely replaced by prominent nodules of varying sizes
§ Contain mix of lipid-poor and lipid-rich cells
§ Evidence of microscopic nodularity
○ Micronodular hyperplasia
§ 1-3mm darkly pigmented micronodules with atrophic intervening areas
§ Pigment believed to be lipofuscin
○ Adenoma or carcinoma
§ Functional adenomas or carcinomas are not morphologically distinct from non-functioning adrenal neoplasms
§ Adenomas
□ Yellow tumours surrounded by thin o well-developed capsules
□ Composed of cells that are similar to those in normal zona fasciculata
§ Carcinomas
□ Larger - 200-300g
□ Unencapsulated
□ Anaplastic characteristics of cancer
36
Causes of primary hyperaldosteronism
○ Bilateral idiopathic hyperaldosteronism
§ Bilateral nodular hyperplasia of aldosterone-secreting zone glomerulus cells of adrenal glands
§ Most common underlying cause
§ Most are sporadic
§ Older individuals
§ Less severe hypertension
○ Adrenocortical neoplasm
§ Aldosterone-producing adenoma (most common) or rarely adrenocortical carcinoma
§ Conn syndrome
□ Solitary aldosterone-secreting adenoma
□ Mid-adult life
□ F:M = 2:1
□ KCNJ5 mutation - encodes potassium ion channel proteins
○ Familial hyperaldosteronism
§ 5% of cases
§ Gene changes
37
Morphology of primary hyperaldosteronism
○ Aldosterone-producing adenomas
§ Solitary small (<2cm) well circumscribed lesions
§ More common on left than right
§ Occur in 30- 40
§ Women more than men
§ Buried within gland
§ Do not produce visible enlargement
§ Bright yellow on cut section
§ Composed of lipid-laden cortical cells that more closely resemble fasciculata cells than glomerulosa cells (normal source of aldosterone)
§ Cells uniform in size and shape
§ Modest nuclear and cellular pleomorphism
§ Spironolactone bodies - found after treatment with antihypertensive spironolactone
○ Bilateral idiopathic hyperaldosteronism
§ Diffuse and focal hyperplasia of cells resembling normal zone glomerulosa
§ Hyperplasia often wedge shaped - extending from peripherally to centre of gland
§ Enlargement subtle
38
Clinical features of primary hyperaldosteronism
○ Hypertension
○ Cardiovascular compromise
§ Left ventricular hypertrophy
§ Reduced diastolic volume
○ Increase in prevalence of stroke and MI
○ Hypokalaemia
○ Diagnosed by elevated ratios of plasma aldosterone concentration to plasma renin activity
39
Define phaeochromocytoma
Tumour of adrenal medulla
- comprised of chromaffin cells (neuroendocrine cells)
- synthesise and secrete catecholamines +/- peptide hormones
- surgical correctable cause of hypertension
40
Clinical features of phaeochromocytoma
○ Of the 90% with HTN, 2/3 have ‘paroxysmal’ episodes of sudden rise in BP, HR & palpitations (can be fatal), headache, sweating, tremor, sense of apprehension
○ Occasionally abdo/chest pain, nausea, vomiting
○ PPT by emotional stress, exercise, change in posture, palpation of tumour
○ Most have chronic, sustained background HTN in addition to paroxysmal symptoms
○ Catecholamine surges can PPT acute CCF, pulmonary oedema, MI, VF and CVA
○ Catecholamine cardiomyopathy: focal necrosis, mononuclear infiltrate, interstitial fibrosis (? Direct effect of catecholamines on myocytes or secondary to vascular constriction-associated ischaemia)
41
Rule of 10s of phaeochromocytoma
○ 10% are extra-adrenal (e.g. carotid body)
○ 10% of sporadic cases are bilateral (50% of familial cases)
○ 10% are malignant (i.e. metastasize)
○ 10% are NOT associated with hypertension
42
Familial syndromes associated with phaeochromocytoma
○ Due to oncogenic germline mutation affecting a least a dozen genes which fall in to two main classes:
○ Those that enhance growth factor receptor pathway signalling (RET, NF1)
○ Those that increase activity and stability of hypoxia-induced transcription factors (HIF-1α, HIF-2α)
○ Patients present at a younger age than sporadic cases
○ More likely to be bilateral
43
Morphological features of phaeochromocytoma
- Gross
○ Weight range: 1g – 4kg (average 100g)
§ Small, intra-adrenal circumscribed lesion
§ Large, haemorrhagic mass, well demarcated by connective tissue or compressed cortical or medullary tissue, necrotic
§ Remnants of adrenal gland stretched over surface
○ Cut section
§ Yellow/tan to large, haemorrhagic, necrotic and cystic
○ Sites of metastasis
§ Regional LNs, liver, lung, bone
- Micro
○ Nest-like clusters of polygonal/spindle-shaped chromaffin cells surrounded by support cells and rich vascular network.
○ Cytoplasmic granules of catecholamines stain with silver stains
○ Nuclei round/ovoid with stippled “salt and pepper” chromatin
○ Usual signs of aggressive/malignant tumour behaviour (mitoses, necrosis, spindle morphology) unreliable predictors of metastatic potential
44
Provide a brief overview of the different multiple endocrine neoplastic syndromes.
- Group of inherited diseases resulting in proliferative lesions of multiple endocrine organs
- Distinct features
○ Occur at younger age
○ Arise in multiple endocrine organs either simultaneously of metachronously
○ Tumours multifocal
○ Preceded by asymptomatic stage of hyperplasia
○ More aggressive and recur at a higher proportion
