Nephrosclerosis
 Disease of the renal arteries.

 Clinical manifestations:
 (1) Benign (arterial) nephrosclerosis →  Caused by the formation of atherosclerotic plaques in the renal artery. Results in narrowing of the arterioles.

(2) Malignant nephrosclerosis → Caused by malignant hypertension. Common signs of malignant hypertension include severe hypertension, retinal hemorrhages, and hypertrophy of the left ventricle. Results in inflammatory changes in the vascular walls, which may lead to rupture of the glomerular capillaries.

INFLUENZA

An acute viral respiratory infection with influenza, a virus causing fever, coryza, cough, headache, malaise, and inflamed respiratory mucous membranes.

Influenza B viruses typically cause mild respiratory disease

Symptoms and Signs

mild cases:

Chills and fever up to 39 to 39.5° C

Prostration and generalized aches and pains, Headache, photophobia and retrobulbar aching

Respiratory tract symptoms may be mild at first, with scratchy sore throat, substernal burning, nonproductive cough, and sometimes coryza. Later, the lower respiratory illness becomes dominant; cough can be persistent and productive.

severe cases

sputum may be bloody. Skin is warm and flushed. Soft palate, posterior hard palate, tonsillar pillars, and posterior pharyngeal wall may be reddened, but no exudate appears. Eyes water easily, and the conjunctiva may be mildly inflamed

Encephalitis, myocarditis, and myoglobinuria are infrequent complications of influenza and, if present, usually occur during convalescence

Infections caused by N. meningiditis

1.  Bacteremia without sepsis.  Organism spreads to blood but no major reaction.

2.  Meningococcemia without meningitis.  Fever, headache, petechia, hypotension, disseminated       intravascular coagulation.  The Waterhouse-Friderichsen Syndrome is a rapid, progressive meningococcemia with shock, organ failure, adrenal necrosis, and death.

3.  Meningitis with meningococcemia.  Sudden onset fever, chills, headache, confusion, nuchal rigidity.  This occurs rapidly.

4.  Meningoencephalitis.  Patients are deeply comatose.

Diagnosis made by examining CSF.

Congenital heart defect
Congenital heart defects can be broadly categorised into two groups,
o    acyanotic heart defects ('pink' babies) :

 An acyanotic heart defect is any heart defect of a group of structural congenital heart defects,  approximately 75% of all congenital heart defects.
 It can be subdivided into two groups depending on whether there is shunting of the blood from the left vasculature to the right (left to right shunt) or no shunting at all.

Left to right shunting heart defects include 
- ventricular septal defect or VSD (30% of all congenital heart defects),
- persistent ductus arteriosus or PDA, 
- atrial septal defect or ASD, 
- atrioventricular septal defect or AVSD.

Acyanotic heart defects without shunting include 
- pulmonary stenosis, a narrowing of the pulmonary valve, 
- aortic stenosis 
- coarctation of the aorta.

cyanotic heart defects ('blue' babies). 
obstructive heart defects

 cyanotic heart defect is a group-type of congenital heart defect. These defects account for about 25% of all congenital heart defects. The patient appears blue, or cyanotic, due to deoxygenated blood in the systemic circulation. This occurs due to either a right to left or a bidirectional shunt, allowing significant proportions of the blood to bypass the pulmonary vascular bed; or lack of normal shunting, preventing oxygenated blood from exiting the cardiac-pulmonary system (as with transposition of the great arteries).

Defects in this group include 
hypoplastic left heart syndrome,
tetralogy of Fallot, 
transposition of the great arteries, 
tricuspid atresia, 
pulmonary atresia, 
persistent truncus arteriosus.
 

Megaloblastic anaemia

Metabolism: B12(cyanocobalamin) is a coenzyme in DNA synthesis and for maintenance of nervous system. Daily requirement 2 micro grams. Absorption in terminal ileum in the presence gastric intrinsic factor. It is stored in liver mainly-

Folic acid (Pteroylglutamic acid) is needed for DNA synthesis.. Daily requirement 100 micro grams. Absorption in duodenum  and jejunum

Causes of deficiency .-

- Nutritional deficiency-
- Malabsorption syndrome.
- Pernicious anaemia (B12).
- Gastrectomy (B12).
- Fish tapeworm infestation (B12).
- Pregnancy and puerperium (Folic acid mainly).
- Myeloproliferative disorders (Folic acid).
- Malignancies (Folic acid).
- Drug induced (Folic-acid)

Features:

(i) Megaloblastic anaemia.
(ii) Glossitis.
(iii) Subacute combined degeneration (in B12deficiency).

Blood picture :

- Macrocytic normochromic anaemia.
- Anisocytosis and poikilocytosis with Howell-Jolly bodies and  basophilic stippling.
- Occasional megalo blasts may be-seen.
- Neutropenia with hypersegmented neutrophills and macropolycytes.
- Thrombocytopenia.
- Increased MVC and MCH with normal or decreased MCHC.

Bone marrow:

- Megaloblasts are seen. They are larger with a more open stippled chromatin. The nuclear maturation lags behind. the cytoplasmic maturation. Maturation arrest is seen (more of early forms).
- Immature cells of granulocyte series are also larger.
 -Giant stab forms (giant metamyelocytes).
 

HYPERTENSIVE VASCULAR DISEASE 

Malignant hypertension 
A small percentage of HTN patients (5%) present with a rapidly rising blood pressure that, if untreated, leads to death within 1 to 2 years. 

systolic pressures -> 200 mm Hg or diastolic pressures -> 120 mm Hg 
Associated with renal failure and retinal hemorrhages
Most commonly is superimposed on preexisting benign hypertension

Hypertension (HTN) has the following complications

- stroke (CVD) 
- multi-infarct dementia
- atherosclerotic coronary heart disease 
- cardiac hypertrophy and heart failure (hypertensive heart disease) 
- aortic dissection 
- renal failure

Essential HTN Accounts for 90% to 95% of all cases

SecondaryHTN 

Renal - > Acute glomerulonephritis Chronic renal disease 
Endocrine - >  Cushing syndrome, Hypothyroidism (myxedema) Hyperthyroidism (thyrotoxicosis) Pregnancy-induced (pre-eclampsia)
Cardiovascular  - > Coarctation of aorta 

Neurologic

Psychogenic,  Increased intracranial pressure 

PATHOGENESIS
most cases (95%) are idiopathic (essential hypertension)
Most of the remaining cases (secondary hypertension) are due to primary renal disease, renal artery narrowing 
Gene defects in enzymes involved in aldosterone metabolism 
 Mutations in proteins that affect sodium resorption as in Liddle syndrome
 
 Genetic factors - > familial clustering of hypertension 
 
 Environmental factors such as stress, obesity, smoking, physical inactivity, and high levels of salt consumption, modify the impact of genetic determinants

Morphology
HTN is associated with arteriolosclerosis (small arterial disease) 

Two forms of small blood vessel disease are hypertension-related: 
1- hyaline arteriolosclerosis 
2- hyperplastic arteriolosclerosis 

Hyaline arteriolosclerosis
Associated with benign hypertension. 
-marked by homogeneous, pink hyaline thickening of the arteriolar walls, and luminal narrowing. 

Hyperplastic arteriolosclerosis
It is more typical of severe hypertension. 
- "onionskin," concentric, laminated thickening of arteriolar walls and luminal narrowing. 
- The laminations consist of smooth muscle cells and thickened, reduplicated basement membrane. 

DISORDERS OF BLOOD VESSEL HYPERREACTIVITY
Several disorders are characterized by inappropriate or exaggerated vasoconstriction of blood vessels: 
1- Raynaud Phenomenon 
2- Myocardial Vessel Vasospasm 

Raynaud Phenomenon
- results from exaggerated vasoconstriction of arteries and arterioles in the extremities (the fingers and toes, but also sometimes the nose, earlobes, or lips). 
-restricted blood flow induces paroxysmal pallor or cyanosis
- involved digits characteristically show "red-white-andblue" color changes from most proximal to most distal 

Myocardial Vessel Vasospasm 

Causes: 1- vasoactive mediators - > prolonged vascular contraction; 
- endogenous (e.g., epinephrine released by pheochromocytomas) or exogenous (cocaine or phenylephrine). 
2- Elevated thyroid hormone -> increase sensitivity of vessels to catecholamines 
3- autoantibodies and T cells in scleroderma vascular instability and vasospasm. 
4- extreme psychological stress (release of catecholamines)

Cardiac raynaud

When vasospasm of cardiac arterial or arteriolar bed is of sufficient duration (20 to 30 min ) myocardial infarction occurs

acute microscopic area of necrosis characterized by mycotic hypercontraction (contraction band necrosis)

subacute and chronic cases - > microscopic foci of granulation tissue or scar