Nephrotic Syndrome
The patient will present with a triad of symptoms:
- Proteinuria, i.e. >3g/24hr-3.5g/24 hr
- Hypoalbuminaemia, i.e. <30g/L
- Oedema 
 >80% of cases are due to glomerulonephritis. In this syndrome, there is damage to podocytes 
 
 Clinical signs
- Pitting oedema, particularly in the limbs and around the eyes; may also cause genital oedema and ascites.
- Possible hypertension 

Causes
- Primary causes – these are diagnoses of exclusion that are only made if secondary causes cannot be found
    o Minimal change disease (MCD)
    o Focal segmental glomerulosclerosis
    o Membranous nephropathy
- Secondary causes – note that these fall into the same three categories as above:
    o Minimal change disease – Hep B, SLE, diabetes M, sarcoidosis, syphilis, malignancy
    o Focal segmental glomerulosclerosis –HIV, obesity, diabetes M, hypertensive nephrosclerosis
    o Minimal change disease –drugs, malignancy, particularly Hodgkin’s lymphoma  
    
 - Differential diagnoses include cardiac failure, i.e. increased JVP, pulmonary oedema and mild proteinuria, and liver disease, i.e. reduced serum albumin.
- The condition causes an increased susceptibility to infection – partly due to loss of immunoglobulin in the urine. Patients tend to be prone to streptococcus infection, as well as bacterial peritonitis and cellulitis.
- Nephrotic syndrome also increases the risk of thromboembolism and hyperlipidaemia.
- The former is due to an increase in the synthesis of clotting factors and to platelet abnormalities, and the latter is a result of increased synthesis of these by the liver to counteract reduced oncotic pressure.  

Investigations

- These are the same as those carried out in GN.
- Also, check for cholesterol as part of confirming the presence of hyperlipidemia.
- Renal biopsy – order this for all adults. In children, because the main cause is minimal change GN, steroids are the first-line treatment. Therefore, in children, biopsy is necessary only if pharmaceutical intervention fails to improve the situation.
- The hypercoagulant state seen in the nephrotic syndrome can be a risk factor for renal vein thrombosis. This can present as loin pain, haematuria, palpable kidney and sudden deterioration in kidney function. This should be investigated with Doppler USS, MRI or even renal angiography.
- Once diagnosed, give warfarin for 3 to 6 months.

Management

- Generally, this involves treatment of the underlying condition which is usually GN. Therefore, fluid management and salt intake restriction are priorities. The patient is usually given furosemide along with an ACE inhibitor and/or an angiotensin II receptor antagonist. Prophylactic heparin is given if the patient is immobile. Hyperlipidaemia can be treated with a statin. 

Nephritic Syndrome 

Acute and chronic
forms of the syndrome exist. The main difference between this and nephrotic syndrome is that in nephritic syndrome haematuria is present. There is also proteinuria, hypertension, uraemia, and possibly oliguria. The two standout features are hypertension and RBC casts. The urine will often appear ‘smoky’ in colour due to the presence of RBC casts. Very rarely, it may appear red 

Causes

1. Post-streptococcal
2. Primary:
- Membranous glomerulonephritis
- Rapidly progressive glomerulonephritis
- IgA nephropathy (Berger’s disease)
3. Secondary
- HSP
- Vasculitis

Clinical Features

- Abrupt onset of :
    o Glomerular haematuria (RBC casts or dysmorphic RBC)
    o Non-nephrotic range proteinuria (< 2 g in 24 hrs)
    o Oedema (periorbital, sacral )
    o Hypertension
    o Transient renal impairment (oliguria, uraemia)
- Urinary casts – these are cylindrical structures produced by the kidney and present in the urine in certain renal diseases. They form in the DCT and collecting duct, dislodging and passing in the urine where they are detected by microscopy. RBC casts are usually associated with nephritic syndrome. The presence of RBCs within a cast is always pathologic and strongly indicative of glomerular damage.
- The proteinuria present is often smaller than in nephrotic syndrome, thus a coexistent condition of nephrotic syndrome is not usually present.
- Encepelopathy may be present, particularly in children, due to electrolyte imbalances and hypertension. This type of presentation is indicative of glomerular damage, but requires renal biopsy to determine the exact problem. In this respect it is similar to nephrotic syndrome.
Overlapping of the two syndromes is possible as nephrotic syndrome may precede nephritic syndrome, although not vice-versa.

Mechanisms of the syndrome vary according to cause; both primary and secondary causes exist. Post-infectious GN is the classic illustration of nephritic syndrome, but the condition may be caused by other glomerulopathies and by systemic diseases such as connective tissue disorders 

Two clinical terms to remember:
- Nephritic syndrome; which comprises edema, proteinuria, hypoalbuminemia, hematuria (smoky urine), oligurua and hypertension.
- Nephrotic syndrome; which comprises of albuminuria, hypoalbuminemia, edema, hyperlipidemia, lipiduria. 

HEALING

Definition. Replacement of damages tissue by healthy tissue. It is an attempt to restore the tissue to structural and functional normalcy.

Healing may be of 2 types

A. Regeneration.

B. Repair by granulation tissue.

A. Regeneration

Where the replacement is by proliferation of parenchymatous cells of type destroyed. This depends upon:

(1) Regenerative capacity of cells. Cells may be :

(a) Labile cells which are constantly proliferating to replace cells continuously shed off or destroyed

Epithelial cells of skin and lining surfaces.

Lymphoid and haemopoietic tissue.

(b) Stable cell. Cells mostly in resting-phase, but capable of dividing when necessary e.g.

• Liver and other parenchymatous and glandular cells.
• Connective tissue cells.
• Muscle cells have a limited capacity to divide.

(c) Permanent cell. These cells, once differentiated are not capable. of  dividing e.g.-nerve

(2) The extent of tissue loss. If  there is extensive destruction including disruption of the framework, complete.regeneration is not possible. even with labile an stable cell

B. Repair by granulation tissue

Granulation tissue is formed by proliferation of surrounding connective tissue elements. which migrate into the site to be repaired.

Granulation tissue formation  seen in :

• Wound healing.
• Organisation of exudates.
• Thrombi.
• Infarcts.
• Haematomas.

The process of repair can be best studied in clean incised wounds, where there is .no or minimal tjssue loss or the_edges or the  edges of the wound are approximated closely as in a surgical wound. This is called Primary union (healing by first intention).

1. The blood in the incised area clots and the fibrin binds the edges together.

2. During the first 24 hours, an acute  inflammation sets in to .bring protein and phagocyte rich exudates to the site.

3. The superficial part of the clot get dry and dehydrated{scab). The surface epithelium proliferates just beyond the cut edges and the cells migrate-deep to dry scab. Epithelialisation is usually complete by 24- 48 hours.

4 Granulation tissue, with actively growing fibroblasts and capillary buds invades the clot (stage of vascularisation). These fibroblasts 'posses contractile myofibrils & hence are termed as myofibroblasts'.

5. Simultaneously, demolition of the debris and clot components takes place.

6 The granulation tissue initially lays down a mucopolysacharide rich ground substance

7.Reticulin and later collagen fibrils are formed by the fibroblasts (with 5 days)

8 with progressive maturation of collagen, some of the capiliary buds develop into arterioles and venules and majority of them are obliterated (stage of devascularisation).

9. With time (weeks to months) the tensile strength of the scar increases and it shrinks.

Secondary union (excised wound-healing by secondary intention).

1. Coagulum forms and fills the gap.

2. Inflammatory reaction is seen as in primary union but is more intense, as a lot more debris has to be removed. .

3. Epithelial proliferation starts covering the surface from the periphery by proliferation beyond the edges and migration under scab.

4.Debridement starts and simultaneously granulation tissue grows into the coagulum from the sides and base of the wound. This is much more exuberant than in primary union. The surface now looks red and granular.

5. Wound contraction. This is early contraction (starts after 3 days and is complete in 2 weeks) and  must be differentiated from contraction after scar formation Wounds can contract by up to 80% of original size of that the gap to be filled is much reduced, resulting in faster healing with a smaller scar.

Wound contraction is probably caused by:

• Dehydration
• Collagen contraction.
• Granulation tissue contraction .(myofibroblasts).

The exact mechanism is not known.

6. Laying down of collagen.

7 Maturation to form a scar which later shrinks and devascularises.

Factors affecting wound healing

Wound healing is delayed by :

A. Local  factors

1. Poor blood supply.

2. Adhesion to bony surfaces (e.g. over the tibia).

3. Persistent injurious agents (infective or particulate) results in chronicity of  inflammation and ineffective healing. .

4. Constant movement (especially in fracture healing).

5. ionizing radiation (in contrast, ultraviolet rays hasten healing).

6. Neoplasia.

B. General factors

I. Nutritional deficiency, especially of.

(i) Protein

(ii) Ascorbic acid (Vitamin C).

(iii) Zinc

2. Corticoids adversely affect wound contraction and granulation tissue formation

(anabolic steroids have a favorable effect).

3. Low temperature.

4. Defects (qualitative or quantitative) in polymorphs and macrophages

.Complication of wound healing

1. Wound dehiscence

2.  Infection

3. Epidermal inclusion (implantation) cysts.

4. Keloid formation

5. Cicatrisation resulting in contract Ires and obstruction(in hollow viscera).

6. Calcification and ossification.

7. Weak scar which could be a site for incisional hernia

8. Painful scar if it involves a nerve twig.

9. Rarely neoplasia (especially in burn scars).

EMBOLISM

Definition: transportation of an abnormal mass of an abnormal mass of undissolved material from one part of circulation to another. The mass transported is called embolus.

Types
I .Thrombi and clots.
2. Gas or air.
3. Fat
4.Amniotic fluid.
5.Tumour

Thromboembolism 
This is the commonest type of embolus and may be formed of the primary thrombus  or more often of propagated clot region which is loosely attached.

Emboli from venous thrombi can result In impaction in the pulmonary  arteries and result in sudden death.
Embolism from cardiac or arterial thrombi results in systemic embolism causing infraction and gangrene.

Gaseous
This occurs when gas is introduced into the circulation:
•    Accidental opening of large veins during surgery.
•    Mismanaged transfusion. .
As air is  readily absorbed into blood only  sudden introduction or large quantities of air produces effects
Caisson’s Disease  bubbling of nitrogen from the blood during sudden decompression as seen during deep sea diving.

Fat Embolism
Causes
•    Fractures especially of long bones and multiple
•    Crush injuries.

Sites of impaction:

o    Lungs.
o    Systemic: causing -
    →    petechial skin haemorrhages.
    →    Embolism to brain leading to coma and death.
    →     Conjunctival and retinal haemorrhages
    
Tumor Embolism.

Invasion of vascular channe1.s is a feature of malignant neoplasms and this leads to:
•    Metastatic deposits,
•    DlC
 

1. Pyogenic liver abscesses may be caused by E. coli, Klebsiella, Streptococcus, Staphylococcus, Bacteroides, Pseudomonas, and fungi. 

Parasitic infections

1. Schistosomiasis is caused by different organisms in different parts of the world.

a. Clinical features include splenomegaly, portal hypertension, and ascites. Lesions are caused by the immune response to ova. 
2. Amebiasis is caused by Entamoeba histolytica. 
a. Clinical features include bloody diarrhea, pain, fever, jaundice, and hepatomegaly.

Drug-induced liver damage may be caused by agents that are direct hepatotoxins, such as carbon tetrachloride, acetaminophen, methotrexate, anabolic steroids, and oral contraceptive pills. 

Actinic keratosis
1. Dry, scaly plaques with an erythematous base.
2. Similar to actinic cheilosis, which occurs along the vermilion border of the lower lip.
3. Caused by sun damage to the skin.
4. Dysplastic lesion, may be premalignant.

Roseola
 - alias exanthem subitum; caused by Herpes virus type 6.
 - children 6 months to 2 years old; spring and fall; incubation 10-15 days.
 - sudden onset of a high fever with absence of physical findings; febrile convulsions are particularly common.
 - fever falls by crisis on the 3rd or 4th day → 48 hours after temperature returns to normal macular or maculopapular rash starting on the trunk and spreading centrifugally.